Practical Radiation

Oncology
Supriya Mallick
Goura K. Rath
Rony Benson
Editors

123
Practical Radiation Oncology
Supriya Mallick • Goura K. Rath
Rony Benson
Editors

Practical Radiation
Oncology
Editors
Supriya Mallick Goura K. Rath
National Cancer Institute Professor, Head NCI-India
All India Institute of Medical Sciences All India Institute of Medical Sciences
Delhi Delhi
India India

Rony Benson
Senior Resident
Regional Cancer Centre
Trivandrum
Kerala
India

ISBN 978-981-15-0072-5    ISBN 978-981-15-0073-2 (eBook)

https://doi.org/10.1007/978-981-15-0073-2

© Springer Nature Singapore Pte Ltd. 2020

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Foreword

The editors of Practical Radiation Oncology need to be commended for com-

piling a succinct and informative handbook. The text integrates the technical
and clinical aspects of radiation oncology. Optimal utilization of radiation as
a cancer therapy requires a clear understanding of the range of issues, and this
book focuses on the basic physics and technical aspects and provides infor-
mation vividly to the clinician involved in radiation therapy planning, par-
ticularly those who are in training and new to practice. The book has been
divided into six parts, covering areas such as instruments, brachytherapy, plan
evaluation, clinical cases and clinical trials.
It is necessary to understand the specific physical and unique clinical
applications of equipment used in radiation oncology. In the first part of the
book, the practical aspects of various machines used are elaborated along
with the quality assurance, personal monitoring, etc. All of these are impor-
tant to understand the effective and appropriate use of radiation as a treatment
modality. This leads to better clinical practice and greater confidence in rec-
ommending radiation treatment with appropriate techniques in a safe and
equally effective manner.
Brachytherapy is an important modality of treatment, especially in several
gynaecological malignancies, and it is an integral part of radiation oncology.
The ‘Practical Brachytherapy’ part integrates different aspect of brachyther-
apy, their basics and site-specific applications. Case selection, procedure,
planning and plan evaluation are discussed. The practical tips provided in this
part will be very useful to the students.
The recent practice of radiation oncology has been revolutionised by tech-
nological advances in radiation delivery and imaging systems. The growing
impact of imaging in radiotherapy planning has provided new insights into
morphological and functional status. There is no doubt that imaging consti-
tutes an extremely important step in radiation therapy management. Finer
aspects of plan evaluation including 3D conformal radiotherapy, IMRT and
tomotherapy have been discussed. Planning images and clinical examples
have also been added so as to bring further clarity into the planning aspects.
The developments in cancer therapy are increasingly arising from studies
in basic science, and understanding of radiobiology plays a significant role.
The ‘Practical Radiobiology’ part has been presented in a concise and inter-
esting way. This will serve as a comprehensive guide in radiobiology related
to radiation oncology.

v
vi Foreword

The exit examination for students appears as an insurmountable problem

for them; this book is conceived and written for medical students preparing
for their examination. Thirteen most relevant cases have been discussed in
each chapter from an exit examination point of view and will be a useful
guide for quick revision. Additionally, this will be an excellent quick refer-
ence for all physicians.
The last part of the book deals with relevant topics in clinical trials, trans-
lational research and radiation toxicity mitigation and treatment in modern
practice of radiation therapy.
The individual chapters in this book are well written and superbly illus-
trated. I congratulate the authors for their successful efforts, as the authors
have gleaned information to make easy reading. Careful attention is given to
the concepts that are crucial in understanding modern techniques. The infor-
mation in this book is presented in a logical and straightforward manner, thus
offering an enjoyable learning experience.
It is a great honour and a privilege for me to write a foreword for this book.
I am confident that many clinicians would significantly benefit from the
information provided by the authors. The data indicate that radiation therapy
continues to be an important modality in the treatment of malignant and a
large number of benign conditions.

March 24, 2019 Shyam Kishore Shrivastava

Director Radiation Oncology
Apollo Hospitals
Navi Mumbai
India
Former Prof & Head Radiation Oncology
Tata Memorial Hospital
Mumbai
India
Preface

Practical Radiation Oncology is long due for the radiation oncology com-
munity. The radiation oncology field has witnessed a paradigm shift in the
last decade and has become a highly sophisticated tech-rich branch of medi-
cal science. It had become increasingly difficult to keep pace with the fast
technical evolution and to know details of technical integrity of modern radia-
tion oncology equipment. Radiation physics and radiobiology have also
evolved to complement our knowledge. Most importantly, clinical applica-
tion is now very much evidence based and versatile. All these necessitate a
book to compile all the necessary information at our fingertips, particularly
for those who are in training and those who have entered the arena of prac-
tice. We realized these aspects and embarked on writing this book, which
deals with practical aspects in practising radiotherapy. We designed the book
in six parts, viz. Practical Physics and Instruments, Practical Brachytherapy,
Practical Planning Aspects and Plan Evaluation, Practical Radiobiology,
Clinical Cases and Other Relevant Topics. In this book, we have tried to
include all the relevant information for day-to-day practice. Being a practi-
cally oriented book, we have added only relevant information regarding the
history of radiation oncology so as not to overburden the reader. The chapters
in the ‘Practical Planning Aspects and Plan Evaluation’ part deal with practi-
cal aspects of how to evaluate a plan systematically with clinical examples, so
that the reader understands each concept better. The chapters on clinical cases
have been added keeping in mind those preparing for examinations as to how
to approach a case including investigations and differentials. Practical plan-
ning aspects have also been added to each chapter including images wherever
possible. These chapters have been prepared mainly for the resident in train-
ing preparing for the exit examination.
The journey started way back in 2016, and it took nearly 2 years to come
to a meaningful end. We realized that this is not the end; rather this is the
beginning of a new journey. We were very careful to deliver correct informa-
tion to the best of our knowledge. We have also kept in mind that the book
should benefit the students who are pursuing a career in radiation oncology.
The presentation has been made very simple so that the reader is not lost in
the crowd of information. At the same time, we believe that for practicing
radiation oncologists the book may serve as a ready source of information.
We have faced few hurdles as it is expected in any good work. However,
we are delighted and feel proud that the guidance of Prof. Rath helped us
immensely to overcome all these hurdles. The book would not have been

vii
viii Preface

p­ ossible without his profound interest. First of all, we express our gratitude to
All India Institute of Medical Sciences, New Delhi, as it gave us the platform
to think for such a book. We are overwhelmed by the response we received
from all the authors across the globe, who wholeheartedly participated in
making this goal achievable in a timely manner. In particular, we express our
deep sense of gratitude to Dr. Nikhil Joshi, Dr. Aruna Turaka and Dr. Kiran
Turaka.
This book has been prepared to the best of our knowledge but there may
be mistakes and shortcomings. But we invite all the reader to come up with
constructive criticism so that we can rectify such weaknesses and make this
book an all-time reference.

Delhi, India Supriya Mallick

New Delhi, India  Goura K. Rath
Trivandrum, India  Rony Benson
Contents

Part I Practical Physics and Instrument

1 Interaction of Radiation with Matter��������������������������������������������   3

Ashish Binjola
2 Practical Aspects of QA in LINAC and Brachytherapy�������������� 13
Seema Sharma
3 Radiation Dosimetry������������������������������������������������������������������������ 21
Seema Sharma
4 Radiation Protection Practical Aspects������������������������������������������ 31
Ashish Binjola
5 Beam Modifying Devices ���������������������������������������������������������������� 41
Supriya Mallick and Goura K. Rath
6 Simulators���������������������������������������������������������������������������������������� 49
Bhanu Prasad Venkatesulu
7 Telecobalt������������������������������������������������������������������������������������������ 51
Rony Benson and Supriya Mallick
8 Gamma Knife ���������������������������������������������������������������������������������� 55
Renu Madan
9 Linear Accelerator �������������������������������������������������������������������������� 63
Supriya Mallick and Rony Benson
10 Helical Tomotherapy������������������������������������������������������������������������ 69
Supriya Mallick and Rony Benson
11 Electrons ������������������������������������������������������������������������������������������ 73
V. R. Anjali
12 Proton Therapy�������������������������������������������������������������������������������� 79
Supriya Mallick
13 Radiation Facility Development����������������������������������������������������� 85
Ritesh Kumar and Divya Khosla
14 Intraoperative Radiotherapy���������������������������������������������������������� 89
Supriya Mallick and Goura K. Rath

ix
x Contents

Part II Practical Brachytherapy

15 Evolution of Brachytherapy������������������������������������������������������������ 95
V. R. Anjali
16 Basics of Brachytherapy and Common Radio Nucleotides���������� 103
V. R. Anjali
17 Brachytherapy in Carcinoma Cervix �������������������������������������������� 109
Prashanth Giridhar and Goura K. Rath
18 Brachytherapy in Head and Neck Cancers ���������������������������������� 117
Supriya Mallick and Goura K. Rath
19 Prostate Brachytherapy������������������������������������������������������������������ 121
Prashanth Giridhar and Aruna Turaka
20 Brachytherapy in Breast Cancer���������������������������������������������������� 129
Ritesh Kumar and Divya Khosla
21 Brachytherapy in Soft Tissue Sarcoma������������������������������������������ 133
Prashanth Giridhar and Susovan Banerjee
22 Surface Mould Brachytherapy ������������������������������������������������������ 139
Rony Benson, Supriya Mallick, and Goura K. Rath

Part III Practical Planning Aspects and Plan Evaluation

23 Plan Evaluation in 3D Conformal Radiotherapy�������������������������� 145

Subhas Pandit
24 Plan Evaluation in IMRT and VMAT�������������������������������������������� 151
Sandeep Muzumder and M. G. John Sebastian
25 Plan Evaluation for TomoTherapy������������������������������������������������ 157
Shikha Goyal and Susovan Banerjee
26 Plan Evaluation in LINAC Based SRS and SABR����������������������� 167
Prashanth Giridhar

Part IV Practical Radiobiology

27 Clinical Significance of Cell Survival Curves�������������������������������� 171

Prashanth Giridhar and Goura K. Rath
28 6Rs of Radiation Oncology�������������������������������������������������������������� 177
Renu Madan and Divya Khosla
29 Radiosensitizers and Radioprotectors�������������������������������������������� 179
Renu Madan
30 Altered Fractionation Radiotherapy���������������������������������������������� 185
Supriya Mallick and Goura K. Rath
31 Therapeutic Index and Its Clinical Significance �������������������������� 191
Rony Benson and Supriya Mallick
Contents xi

Part V Clinical Cases

32 Carcinoma Cervix���������������������������������������������������������������������������� 195

Rony Benson, Supriya Mallick, and Goura K. Rath
33 Case Carcinoma Breast ������������������������������������������������������������������ 201
Rony Benson, Supriya Mallick, and Goura K. Rath
34 Oral Cavity Carcinoma ������������������������������������������������������������������ 211
Prashanth Giridhar, Supriya Mallick, and Goura K. Rath
35 Oropharynx Cancer������������������������������������������������������������������������ 217
Nikhil P. Joshi and Martin C. Tom
36 Laryngeal Cancer���������������������������������������������������������������������������� 225
Subhas Pandit and Simit Sapkota
37 Parotid Tumour�������������������������������������������������������������������������������� 231
V. R. Anjali
38 Extremity Soft Tissue Sarcoma������������������������������������������������������ 239
Supriya Mallick and Goura K. Rath
39 Orbital Tumors and Retinoblastoma �������������������������������������������� 245
Kiran Turaka and Aruna Turaka
40 Carcinoma Rectum�������������������������������������������������������������������������� 255
Bhanu Prasad Venkatesulu
41 Carcinoma Anal Canal�������������������������������������������������������������������� 259
Bhanu Prasad Venkatesulu
42 Skin Cancer�������������������������������������������������������������������������������������� 263
Nikhil P. Joshi and Martin C. Tom
43 Lymphoma���������������������������������������������������������������������������������������� 269
Rony Benson, Supriya Mallick, and Goura K. Rath
44 Carcinoma Lung������������������������������������������������������������������������������ 275
Sandeep Muzumder and M. G. John Sebastian

Part VI Other Relevant Topics

45 Critical Appraisal of a Clinical Trial���������������������������������������������� 285

Bhanu Prasad Venkatesulu
46 Radiation Toxicity���������������������������������������������������������������������������� 287
Supriya Mallick, Rony Benson, and Goura K. Rath
47 Cancer in India�������������������������������������������������������������������������������� 299
Supriya Mallick, Chitresh Kumar, Rony Benson,
and Goura K. Rath
About the Editors

Supriya Mallick is currently an Assistant Professor of Radiation Oncology

at the National Cancer Institute-India, AIIMS, New Delhi. He is a graduate of
Calcutta Medical College and received his MD from AIIMS. His chief
research interests are in neuro-oncology and head and neck oncology. He has
published numerous papers in national and international journals.

Goura K. Rath is currently Director of the National Cancer Institute-India,

AIIMS, New Delhi, and Chief of Dr. B R Ambedkar Institute Rotary Cancer
Hospital (DRBRAIRCH) at AIIMS. He has published more than 300 papers
in peer-reviewed national and international journals and is the editor of the
Textbook of Radiation Oncology.

Rony Benson is currently pursuing his training in medical oncology at the

Regional Cancer Center, Trivandrum. His chief research interests are in
gynae-oncology and head and neck oncology. He has published several
papers in national and international journals.

xiii
 Part I
Practical Physics and Instrument
 Interaction of Radiation
with Matter 1
Ashish Binjola

The basics of physical aspects of radiation oncol- 1.1  asic Physics Concepts
B
ogy, radiodiagnosis, and nuclear medicine lie in to Understand Basic
how various types of radiation interact with mat- Interactions
ter. In radiation oncology, megavoltage X- and
gamma rays and high energy electrons are used Atomic Structure An atom is a basic structure
for the treatment of the malignant disease (some- from which all matter is composed, in the same
times benign as well). For the simulation and way as a brick is a basic structure from which a
verification of the treatment, use of kilovoltage wall is built. Atom is derived from the Greek
X-rays (CT and conventional simulators, cone word Atomos means “indivisible” as it was
beam CT, etc.) is a routine practice. More exotic thought to be anciently, but today we know that it
heavy ion therapies, with proton (i.e., hydrogen has substructure.
nucleus), carbon ion, and other heavier charged The atom is composed of: positively charged
particles, are capable of providing treatment (+) protons and electrically neutral neutrons
plans with higher conformality of the dose to the inside the nucleus and negatively charged (−)
target volume and better normal tissue sparing. electrons orbiting around the nucleus. The
Tumor biological information in the form of nucleus determines the identity of the element as
PET-CT functional imaging augment for better well as its atomic mass. The nucleus constitutes
delineation of target volumes in many sites/types almost 99.9% of an atom’s mass but size of the
of malignancies (e.g., involved-site radiation nucleus is very small (nuclear radius is approxi-
therapy). mately 10−15 m) compared to the size of the
This chapter introduces the basic physics of whole atom (the size of an atom is approximately
radiation interactions with the matter briefly 10−10 m), so most of the atom is empty space
along with its practical aspects in radiation with electrons in fixed shells, revolving around
oncology. the nucleus.
Each element has a unique atomic number
(number of protons inside the nucleus). Proton
number never changes for any given element. For
example, the Carbon atom has an atomic number
of six indicating that carbon always has six
protons.
A. Binjola (*) Neutrons are the other constituent particles of
Department of Radiation Oncology, AIIMS, the nucleus of an atom. Unlike protons and
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 3

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_1
4 A. Binjola

e­lectrons, neutrons do not possess any charge Classification of Radiation Radiation can be
(electrically neutral) classified into ionizing (having energy more than
that is required to ionize an atom) and non-­
Atomic mass no A = Z + N ionizing. Visible light, radio waves (used for tele-
Z- Atomic Number (number of protons inside the communications), microwaves are some
nucleus); N- Number of neutrons inside the examples of non-ionizing radiations.
nucleus.
Electrons are negatively charged particles that Ionizing radiation can further be classified as:
surround the nucleus in “orbits” or “shells.”
These electrons revolve around the nucleus in 1. Directly Ionizing Radiation: Energetic
well-defined orbits like planets revolving around charged particles are the directly ionizing
the sun. radiation as it ionizes matter when it inter-
Basic properties of atomic particles are sum- acts with atoms by ionization and excita-
marized in Table 1.1. tion. Protons, alpha particles, and electrons
Neutrons and protons are together called the are examples of directly ionizing
nucleons and they are made up of particles known radiation.
as quarks. There are six known quarks which are the 2. Indirectly Ionizing Radiation:
constituent particles of hadron (protons, neutrons, Electromagnetic radiation (X-rays, gamma
etc.) particles. These quarks are held inside the had- rays, and high energy spectrum of UV rays)
ron particle by exchange particles gluons. The and neutrons are examples of indirectly ion-
atomic structure of an atom is shown in Fig. 1.1. izing radiation.

Table 1.1 Basic properties of atomic particles

Atomic constituent Energy equivalence of rest
particle Charge Rest mass mass Location
Electron −1.6 × 10−19 9.1 × 10−31 kg 0.511 MeV/C2 Orbiting around the
coulomb nucleus
Proton +1.6 × 10−19 1.673 × 10−27 kg 938.28 MeV/C2 Inside the nucleus
coulomb
Neutron Electrically 1.675 × 10−27 kg 939.57 MeV/C2 Inside the nucleus
neutral

Fig. 1.1 Atomic

structure: In an atom, Electrons
electrons revolve around
the nucleus

Nucleus
n
p

Atomic Shell or orbit

1 Interaction of Radiation with Matter 5

1.1.1 Electromagnetic Radiation ation of ion pair is called ionization. Maximum

energy transfer happens during a head-on
Electromagnetic radiation is the form of energy, collision.
which can traverse in the vacuum with the speed If the ejected electrons have sufficient ener-
c ≈ 3 × 108 m/s, in which electric and magnetic gies for further ionization, it is known as delta
field vectors are orthogonal to each other as well rays.
as to the direction of propagation. Speed of elec-
tromagnetic radiation in the medium is lesser Specific Ionization Specific Ionization is
than its speed in vacuum and depends on the defined as the number of ion pairs produced per
refractive index of the medium. Figure 1.2 shows unit path length by the charged particles. Specific
graphical representation of electromagnetic radi- ionization increases with the square of the charge
ation waveform. of the particle and decreases with the square of
the particle velocity. It is represented by lp/mm.
alpha particles have higher specific ionization
1.1.2 Interaction of Charged compared to the electrons. Higher specific ion-
Particles with Matter ization eventually leads to higher absorbed dose
in the medium.
Excitation Charged particles directly interact When highly energetic heavy charged parti-
with the atomic electron and transfer energy that cles traverse the matter, specific ionization and
is less than the binding energy of the electron. hence dose deposition in the medium increases to
The electron goes to the higher energy state and the maximum as the particles slow down at the
while returning to the ground state it emits energy end of their track. This phenomenon is responsi-
in the form of electromagnetic radiation. ble for the Bragg peak of heavy charged particles.
Doses to either side of the Bragg peak is quite
Ionization When charged particle transfers lower compared to dose at or very near to the
energy more than the binding energy of the Bragg peak.
orbital electron, it ejects the electron from the When electrons pass through the matter due to
atom making it positively charged, while the their lightweight, undergo multiple scattering,
ejected electron is negatively charged. This cre-

Direction of
Electric field

λ = Wavelength

Direction of
Magnetic field
Direction of Propagation

Fig. 1.2 Representation of electromagnetic radiation waveform

6 A. Binjola

Fig. 1.3 Absorbed dose

vs. depth for heavy
charged particles
Bragg Peak

Absorbed Dose

Depth

and move in tortuous path, that is why electrons Alpha particles are comparatively heavier in
do not exhibit Bragg peak (Fig. 1.3). mass and emitted with the same energy by the
nuclei of a particular isotope (e.g., 4.05 MeV for
Stopping Power Stopping power is the property Th-232). Alpha particles lose energy in tissue
of the matter in which a beam of charged parti- very rapidly (within few micrometers). Specific
cles traverses. When charged particles interact ionization and LET are very high for alpha parti-
with matter, their energy loss mainly depends on cles. On the other hand, electrons are approxi-
properties of the particle (mass, energy, etc.) as mately 1/7300 times lighter than alpha particle
well as the absorber. For a particle beam, the rate (and 1/1840 times lighter than the proton) with
of energy loss per unit path length in an absorb- unit “–”ve charge, therefore electrons are scat-
ing medium is called the linear stopping power tered more easily and have a tortuous path in the
(−dE/dl, usually expressed in units MeV/cm). matter. Electrons can traverse into the tissue more
Dividing linear stopping power by the den- than alpha particles, with lower specific ioniza-
sity ρ of the absorber results in the mass stop- tion and linear energy transfer and come to rest
ping power S. (Expressed in units of MeV · cm2 after traversing the medium a distance known as
· g−1). range which depends on electrons energy and the
In the viewpoint of a charged particle interact- density of tissue (range of 10 MeV electrons
ing with matter, we can classify stopping power from the Linac is approx. 5.0 cm in soft tissue
into two types: and lesser in bone).

1. Radiative stopping power and

2. Collision stopping power 1.1.3 Radiative Interaction
of Charged Particles
Linear Energy Transfer (LET) It is the energy
absorbed in the medium per unit path length of When a highly energetic charged particle passes
the particle. LET is expressed in keV/μm. The close to the nucleus of an atom, it undergoes
concept of LET is important as biological effects deflection and loses part of its energy in the form
depend on the rate of energy absorption in the of electromagnetic radiation known as
medium. Bremsstrahlung radiation (breaking radiation).
1 Interaction of Radiation with Matter 7

Bremsstrahlung interaction increases with the

square of atomic number (Z2) of the medium and
decreases with increase in the square of mass
(m2) of the particle. As it is strongly dependent on
the mass of the particle, heavier charged particles
produce lesser amount of bremsstrahlung X-rays
when compared with lighter particles. That is
why electrons are the most efficient and widely
used for generating X-rays.

1.2 Interaction
of Electromagnetic
Fig. 1.4 Rayleigh scattering: no change in the energy of
Radiation scattered photon

Electromagnetic radiation has neither charge nor

mass and it ionizes the matter indirectly after pro- and decreases with the photon energy.
ducing secondary electrons. Electromagnetic Scattered photons do not carry any informa-
radiation undergoes following types of interac- tion and only degrade the image quality if
tions with matter: detected. So, Rayleigh scattering is highly
undesirable interaction.
1. Rayleigh scattering
2. Photoelectric absorption
3. Compton scattering 1.2.2 Photoelectric Absorption
4. Pair production
5. Pair annihilation When the X- or gamma-ray photon interacts with
6. Photodisintegration a bound electron of an atom, all the energy of the
photon is transferred to the atomic electron, the
The probability of these interactions depends electron is ejected from its shell and the photon is
mainly upon the energy of the radiation and the completely absorbed.
atomic number of the matter. The vacancy thus created by the ejection of
the electron is immediately filled by outer shell
electron and in this process, the energy differ-
1.2.1 Rayleigh Scattering ence between the two shells is emitted as charac-
teristic X-rays (X-ray energies are characteristics
It is also known as classical or coherent scat- of the atom). If the characteristic X-rays interact
tering. In this type of interaction X- or γ ray with other atomic electron and electron is get-
photon is absorbed by an atom following ting ejected by the absorption of the X-ray, this
which it goes to higher energy state and ejects electron is called Auger electron.
out the photon with the same energy in a The probability of photoelectric absorption
slightly different direction, as it comes to its decreases with the increase of photon energy
ground state. As there is no loss of photon (approximately ∝ 1 ) but increases as the
energy taking place, it is also called inelastic E3
scattering. The probability of Rayleigh scat- atomic number of the medium increases (approx-
tering (Fig. 1.4) at low KV diagnostic energy imately ∝ Z3). The probability of photoelectric
range is less than 5% (e.g., mammography). absorption is the maximum when the photon
This kind of interaction is more probable with energy is only slightly more than the B.E. of inner
high Z material compared to low Z materials shell electron, known as the k edge.
8 A. Binjola

A photon of energy hν will release an electron mode of interaction in water equivalent material
with kinetic energy Ee = hν – B.E., where B.E. is for high energy photons (30 KeV to 24 MeV).
the binding energy of the electron.
Photoelectric absorption is the key interaction h
at low diagnostic energies (Fig. 1.5). Differential ∆λ = λ ′ − λ = (1 − cos ∅ ) ,
mc
absorption of X-rays in different body tissues is
the important principle for the formation of diag-
nostic images; however, at MV energies of radio-
therapy, this interaction is negligible (Fig. 1.6). 1.2.3  air Production and Pair
P
Annihilation
Compton Scattering In Compton scattering
(inelastic scattering), a part of the energy of the Pair production and pair annihilation are exam-
incident photon is transferred to a free electron. ples of mass and energy equivalence.
Free electron means, its binding energy is very When a photon having energy more than
less compared to the energy of the incident pho- 1.022 MeV interacts with the nuclear field, it gets
ton. Photon transfers only a part of its energy to completely disappeared and there is a particle
the electron and gets scattered at an angle with (electron) and its antiparticle (positron) known as
reduced energy. Before coming to rest, the electron–positron pair. An antiparticle is same as
Compton electron deposits its energy in the its particle in mass and other properties but it has
medium. Compton scattering is independent of opposite charge.
atomic number (Z) and depends on the electron Threshold photon energy required for the pair
density of the medium. The probability of this production is 1.022 MeV. Excess energy is shared
interaction decreases with increase in energy (E) as kinetic energies between the electron and the
of the incident photon but it is the predominant positron.

Fig. 1.5 Photoelectric Characteristic

absorption X - rays

Incident photon

Deflected photo electron

1 Interaction of Radiation with Matter 9

Fig. 1.6 Compton Compten

scattering electron

θ
Incident
Photon
φ

Scattered
n Photon
p

Positron continuously loses its energy in the inside the Linac room because of photodisinte-
medium and encounters an electron & the two gration as some high energy photons when inter-
particles annihilate to produce two photons in acting with Linac head causes
flight, each of energy 0.511 MeV in opposite photodisintegration.
direction (for the conservation of momentum).
This interaction is known as the pair annihilation.
The pair annihilation process is the principle 1.2.5  inear Attenuation Coefficient
L
behind the positron emission tomography (PET). and Mass Attenuation
The probability of pair production increases Coefficient
with increasing photon energy beyond the thresh-
old (1.022 MeV) and also with the square of When gamma radiation traverses through matter
atomic number (Z2) of the atom. There is no pair it undergoes all the described interactions with
production in the diagnostic energy range, in different probabilities which depend on the
megavoltage radiotherapy, pair production energy of the photons as well as on other proper-
accounts for 6–20% approximately (Fig. 1.7). ties (atomic number, density, electron density,
etc.) of the matter.
When the radiation traverses through the mat-
1.2.4 Photodisintegration ter, its intensity reduces as it passes through the
matter. For a point source of monoenergetic radi-
In this interaction, a very high energy photon ation, when it passes through an absorber it
(energy greater than 10 MV) interacts with the undergoes exponential attenuation.
nucleus of an atom in such a way that it is com-
I = I 0 e− µ x
pletely absorbed by the nucleus. Nucleus goes
into the excited state and there is ejection of one where I0—incident intensity of the radiation; I—
or more particles (neutron, alpha particle, etc.). intensity transmitted after passing through the
The probability of photodisintegration absorber; X—the thickness of the absorbing
increases with photon energy and it is more prob- material; and μ—linear attenuation coefficient.
able with high Z materials. If x is expressed in cm, μ is expressed in per
When we treat patients using 10 MV, 15 MV, cm (cm−1) and is called linear attenuation coeffi-
or higher energies, there is neutron production cient. The quantity μ/ρ is called mass attenuation
10 A. Binjola

e– ε = 0.511 Mev

e+
€ > 1.022 e–

Mev

ε = 0.511 Mev
e+

Pair Production

Pair annihilation

Fig. 1.7 Pair production and pair annihilation

coefficient; where ρ is the density of the medium, undergo interaction with nuclei of the atoms.
it is expressed in cm2/g. Important interactions are:

Half Value Layer (HVL) and Tenth Value 1. Elastic collision

Layer (TVL) The term half value layer (HVL) 2. Inelastic collision
defined as the thickness of an absorber required 3. Radiative capture
to attenuate the intensity of the beam to half its 4. Neutron capture (producing other particles)
original value. HVL we can express using given 5. Nuclear fission
formula

Elastic Collision In this type of interaction total

HVL = ln 2 / µ or 0.693 / µ
kinetic energy of the neutron and the target nucleus
TVL is the thickness of material that attenuate remains the same before and after the collision.
X-ray beam by 90% and transmits only one tenth Some of the energy of the neutron is given to the
of incident intensity. nucleus. As per the conservation of energy and
momentum principles, the maximum energy trans-
TVL = ln 10 / µ or 2.305 / µ
fer will occur for the nucleus of an approximately
One TVL is approximately equal to the 3.33 equal weight of the particle. That is why hydroge-
HVL of attenuating material. For designing a nous materials are effective absorbers for neutrons.
shielding block, approximately 5 HVL is required.

Inelastic Collision When a high energy neutron

1.3 Interaction of Neurons interacts with a heavy nucleus, the neutron is
with the Matter absorbed by the target nucleus and an excited
compound nucleus is formed. Neutron is re-­
Interaction of neutrons: Neutrons are electrically emitted with less energy as the nucleus de-excites
neutral and indirectly ionizing particles. Neutrons to ground state by emitting gamma rays. e.g., X
are unaffected by coulombic fields. Neutrons (n, n γ) Y.
1 Interaction of Radiation with Matter 11

Radiative Capture Neutron is captured by the to the normal state. This kind of interaction is
target nucleus and forms a compound nucleus more probable at very high energy of neutrons.
which is in the excited state, and then the target
nucleus decays to the ground state by emission of
gamma radiation. E.g., Production of 60Co in Nuclear Fission In this process, the absorption
nuclear reactor 59Co (n, γ) 60Co. Radiative capture of the neutron causes a heavy fissionable nucleus
is more probable with low energy neutrons. to split into two lighter nuclei. Many fission prod-
ucts (radioisotopes 99Mo, 131I, 32P, etc.) are very
Neutron Capture Neutron is captured by target useful in medicine for diagnosis and therapy.
nucleus and forms a compound nucleus which is Fission reaction, e.g.,
in an excited state due to the capture of a neutron,
and then the compound nucleus emits charged
U 235 + 0 n1 → 30 n1 + 36 Kr 92 + 56 Ba141 + energy
particle like proton or alpha particles and comes 92
 Practical Aspects of QA in LINAC
and Brachytherapy 2
Seema Sharma

2.1 Introduction to doing quality assurance steps, documentation

and maintaining log book is essential for each
Radiotherapy treatment involves many steps radiation therapy equipment.
from immobilization of the patient, imaging, Proper quality assurance at every step involv-
planning, treatment, and daily verification. ing in radiotherapy can minimize the uncertain-
Quality assurance at all the steps is required to ties in overall treatment delivery; thereby ensure
ensure that what has been planned and prescribed, that patient gets what is planned. QA reduces
being delivered to the patient. Lack of proper the probability of accidents and errors and helps
quality assurance can lead to tumor under dosing in optimizing tumor control and limits normal
as well as excess dose to normal tissues. tissue toxicity. Any discrepancy found during
Medical physicist is primarily responsible for routine QA should be investigated and
physical and technical aspects of the quality corrected.
assurance. However, close coordination among
physicist, technologist, and oncologist is neces-
sary to ensure the quality treatment to the patient. 2.2  inear Accelerator Quality
L
Quality assurance (QA) starts from preparing Assurance
specification for the radiotherapy equipment to
be ordered. Once equipment has been purchased, 2.2.1 Acceptance of Linear
acceptance test is performed to determine the Accelerator
baseline standard. Radiation equipment should
undergo extensive baseline checks after any Acceptance testing has to be done once the
major repair to ensure the compliance with the LINAC installation is over; vendor has to per-
purchase specifications. Initial calibration and form the entire test as per the requirement of the
commissioning of the equipment is the next technical specification agreed at the time of pur-
major step and is often time consuming. After chase. Usually vendor performs the tests as per
commissioning of the equipment, periodic qual- the company’s acceptance format, after that any
ity assurance steps must be done as recommended additional test or requirements as per purchase
by national or international protocol. In addition order specification has to be completed.
Institution physicist has to accept the LINAC
technically (as per specification) before
S. Sharma (*) commissioning.
Department of Radiation Oncology, AIIMS,
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 13

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_2
14 S. Sharma

Usual tests performed for acceptance testing is the responsibility of the physicist; physicist
are radiation survey, jaw symmetry, coincidence will measure all the beam data (required for beam
of light beam with X-ray beam, mechanical iso- modeling) and fed in to the treatment planning
center stability with rotation of collimator and system as per the protocol. After measurement
gantry, stability of radiation isocenter with and before using the LINAC for patient treat-
respect to gantry and couch rotation, multileaf ment, physicist has to validate the commissioned
collimator (MLC) quality assurance, X-ray beam LINAC along with its TPS using AAPM
flatness, symmetry and percentage depth dose (American Association of Physicist in Medicine)
(PDD), accuracy of optical distance indicator, TG (Task Group)-119 end-to-end test. End-to-­
table top sagging, field size indicator, etc. end test validation is necessary because if there is
any problem at any step in commissioning that
will be detected during end-to-end test and that
2.2.2 Commissioning of Linear will ensure that all the systems are configured
Accelerator with each other properly.
AAPM TG-106 gives the extensive guidelines
After acceptance test, more data has to be for commissioning of medical linear accelera-
acquired before clinical use of LINAC, the pro- tors. Various tests are described in TG106, some
cess is known as commissioning. Commissioning major tests are tabulated in Table 2.1 [1].

Table 2.1 Major tests for commissioning a medical accelerator

Data Description
Calibration Dose per monitor unit calibration of all modalities and energies according to current
protocol
Depth dose Central axis depth dose distribution for all modalities and energies, sufficient number of
field sizes to allow interpolation of data
Profiles Transverse, longitudinal, and diagonal dose profiles for all modalities and energies at dmax
for electrons and selected depths for photons (e.g., dmax, 5, 10, and 20 cm); all cones for
electrons and selected field sizes for photons (e.g., 5 × 5, 10 × 10, and 40 × 40 cm2)
Isodose distribution Isodose curves for all modalities and energies, all cones for electrons and selected field
sizes for photons (e.g., 5 × 5, 10 × 10, 40 × 40 cm2), all wedge filters for selected field sizes
(e.g., 5 × 5, 10 × 10 cm2, maximum)
Output factors Sc, and Sp factors as a function of field size for all photon energies: output factors for all
electron energies, cones, and standard inserts; tray transmission factors and wedge
transmission factors
Off-axis ratios A table of off-axis ratios for all photon energies as a function of distance from central axis;
these data may be obtained from dose profiles for a 5 × 40-cm field at selected depths (e.g.,
dmax, 5, 10, 20 cm)
Inverse square law Verification of inverse square law for all photon energies, virtual source position for all
electron energies, and effective SSD for all electron energies and cones
Tissue–phantom Direct measurement of TPRs/TMRs for all photon energies and selected field sizes (e.g.,
ratios 5 × 5, 10 × 10, 40 × 40 cm) and depths (5, 10, 30 cm) for verification of values calculated
from percent depth doses
Surface and build-up For all photon energies and selected field sizes (5 × 5, 10 × 10, 30 × 30, and 40 × 40 cm2),
dose percent surface dose for all electron energies for a 10 × 10-cm cone
Treatment planning Beam data input, generation, and verification of central axis percent depth dose and TPR/
system TMR tables; sample isodose curves (e.g., 5 × 5, 10 × 10, maximum) for unwedged,
wedged, asymmetric, and blocked fields; sample isodose curves for multiple field plans
using rectangular and elliptical contours; electron beam depth dose data; isodose curves for
all cones and sample isodose curves on rectangular and circular contours
Special dosimetry Data for special techniques such as total body irradiation, total skin irradiation, stereotactic
radiosurgery, intraoperative electron therapy, etc.
SSD source to surface distance, TMR tissue–maximum ratio, TPR tissue–phantom ratio
2 Practical Aspects of QA in LINAC and Brachytherapy 15

2.2.3  eriodic Quality Assurance

P 2.3 Brachytherapy Quality
of Linear Accelerator Assurance

Periodic quality assurance programme is essen- Remote afterloading brachytherapy is very

tial to maintain the radiation machines within its sophisticated and standard practice. Remote
acceptable performance standards. Various afterloading machine minimizes the exposure to
reports/publications are available on quality the personal handling the procedure. Remote
assurance of linear accelerator (LINAC) and afterloading machines are available based on dif-
numerous protocols are also available for special- ferent dose rates, i.e., low dose rate (LDR), high
ized procedures and equipments, i.e., (1) AAPM dose rate (HDR).
TG-24, Physical aspect of quality assurance in
radiotherapy (1984), (2) World Health
Organization quality assurance in radiotherapy 2.3.1 Acceptance of Brachytherapy
(1988), (3) AAPM TG-40, Comprehensive QA (Remote Afterloading)
for radiation oncology (1994), (4) IAEA, Setting
up a radiotherapy program (2008), (5) AAPM Objective of performing the acceptance testing is
TG-142, Quality assurance of medical accelera- to ensure that the brachytherapy equipment fulfils
tors (2009), (6) AAPM, Guidance document on the purchase order specification. The acceptance
delivery, treatment planning, and clinical imple- testing of the remote afterloading machine can be
mentation of IMRT, (7) AAPM TG-25 and categorized in four parts as per Glasgow et al.: (1)
AAPM TG-20, Recommendations for clinical operational testing, (2) radiation safety check, (3)
electron beam dosimetry, (8) AAPM TG-42, testing of source calibration and transport, and (4)
Stereotactic radiosurgery, (9) AAPM TG101, testing of treatment planning software [3].
Stereotactic body radiation therapy, (10) AAPM Some recommended tests by Glasgow et al.
TG-135, Quality assurance for robotic surgery, are tabulated below (Table 2.5):
(11) AAPM TG-148, Quality assurance for heli-
cal tomotherapy, etc.
AAPM TG-142 is most widely used protocol 2.3.2  eriodic Quality Assurance
P
to check the LINAC performance. TG-142 report of Brachytherapy (Remote
suggests various types of the tests (i.e., mechani- Afterloading)
cal, radiation, safety) and the frequency of the
tests with their respective tolerances [2]. Quality assurance procedures have to be estab-
Some of the tests recommended by AAPM lished for the remote afterloader unit and its
TG-142 are tabulated below (Tables 2.2, 2.3, and 2.4): ancillary accessories, for the process of clinical

Table 2.2 AAPM TG-142 daily QA

Category Procedure Non-IMRT IMRT SRS/SBRT
Dosimetry X-ray output constancy (all energies) 3% 3% 3%
Dosimetry Electron output constancy (weekly test) 3% 3% 3%
Mechanical Laser localization 2 mm 1.5 mm 1 mm
Mechanical Distance indicator (ODI) at isocenter 2 mm 2 mm 1 mm
Mechanical Collimator size indicator 2 mm 2 mm 1 mm
Safety Door interlock Functional Functional Functional
Safety Door closing safety Functional Functional Functional
Safety Audiovisual monitors Functional Functional Functional
Safety Stereotactic area monitor NA NA Functional
Safety Radiation area monitor Functional Functional Functional
Safety Beam on indicator Functional Functional Functional
16 S. Sharma

Table 2.3 AAPM TG-142 monthly QA

Category Procedure Non-IMRT IMRT SRS/SBRT
Dosimetry X-ray output constancy 2% 2% 2%
Dosimetry Electron output constancy 2% 2% 2%
Dosimetry Backup monitor chamber constancy 2% 2% 2%
Dosimetry Typical dose rate constancy NA 2% 2%
Dosimetry Photon beam profile constancy 1% 1% 1%
Dosimetry Electron beam profile constancy 1% 1% 1%
Dosimetry Electron beam energy constancy 2%/2 mm 2%/2 mm 2%/2 mm
Mechanical Light/radiation field coincidence 2 mm/1% an a 2 mm/1% an a 2 mm/1% an a
side side side
Mechanical Light/radiation field coincidence 1 mm/1% an a 1 mm/1% an a 1 mm/1% an a
side side side
Mechanical Distance check device for lasers compared 1 mm 1 mm 1 mm
with front pointer
Mechanical Gantry/collimator angels indicator 1.0° 1.0° 1.0°
Mechanical Accessory trays 2 mm 2 mm 2 mm
Mechanical Jaw position indicators (symmetric) 2 mm 2 mm 2 mm
Mechanical Jaw position indicators (asymmetric) 1 mm 1 mm 1 mm
Mechanical Cross-hair centering (walkout) 1 mm 1 mm 1 mm
Mechanical Treatment couch position indicators 2 mm/1.0° 2 mm/1.0° 1 mm/0.5°
Mechanical Wedge placement accuracy 2 mm 2 mm 2 mm
Mechanical Compensator placement accuracy 1 mm 1 mm 1 mm
Mechanical Latching of wedges/blocking tray Functional Functional Functional
Mechanical Localization lasers 2 mm 1 mm 1 mm
Safety Laser guard interlock Functional Functional Functional

use of the equipment, e.g., proper execution of a extensive procedures of quality checks and their
planned treatment. frequencies.
Quality assurance tests are designed to con- Some of the periodic tests recommended by
firm that the system (remote afterloading unit, ESTRO (European Society for Therapeutic
facility, applicators, sources, etc.) performs Radiology and Oncology) Booklet-8 are tabu-
within the tolerances established during the lated below [5] (Table 2.6):
acceptance tests (AAPM TG-41) [4]. In some The daily quality check should be executed
cases quality assurance test procedure is identical on a routine basis before treating the first
to the acceptance test procedure; on the other patient of the day. Starting the treatment may
hand, less rigorous quality assurance tests are implicitly assume that daily tests were per-
performed. Various protocols and guidelines are formed and that the results were satisfactory,
available for periodic quality assurance. AAPM according to a department’s quality assurance
Report-13, Physical Aspects of Quality Assurance protocol. User departments may develop spe-
in Radiation Therapy recommends quality assur- cial daily check forms to record and sign for the
ance procedures for both conventional and remote execution of these tests on satisfactory
afterloaders in brachytherapy. AAPM Task Group completion.
40 has a draft document (1992) on comprehen- Brachytherapy software (treatment planning
sive quality assurance procedures that includes a system) testing includes verification of dose dis-
chapter on quality assurance for conventional tribution around the single and multiple sources
manual brachytherapy and remote afterloaders. and matches the software generated dose distri-
ESTRO Booklet-8: a practical guide to quality bution with published tables. One should also
control to brachytherapy equipment gives the verify the decay correction applied by the soft-
2 Practical Aspects of QA in LINAC and Brachytherapy 17

Table 2.4 AAPM TG-142 annual QA

Category Procedure Non-IMRT IMRT SRS/SBRT
Dosimetry X-ray and electron flatness 1% 1% 1%
change from baseline
Dosimetry X-ray and electron symmetry 1% 1% 1%
change from baseline
Dosimetry SRS arc rotation mode; MU NA NA 1.0MU or 2%
setting vs delivered
Dosimetry SRS arc rotation mode; gantry NA NA 1.0 degree or 2%
arc setting vs delivered
Dosimetry X-ray/electron output 1% 1% 1%
calibration (TG-51)
Dosimetry Spot check of field size 2% for <4 × 4 cm2 2% for <4 × 4 cm2 2% for <4 × 4 cm2
dependent output factors 1% for ≥4 × 4 cm2 1% for ≥4 × 4 cm2 1% for ≥4 × 4 cm2
Dosimetry Output factors for electron 2% 2% 2%
applicators
Dosimetry X-ray beam quality (PDD10 or 1% 1% 1%
TMR2010)
Dosimetry Electron beam quality (R50) 1 mm 1 mm 1 mm
Dosimetry Physical wedge transmission 2% 2% 2%
factor
Dosimetry X-ray MU linearity (output 2% ≥ 5MU 5% (2-4MU), 5% (2-4MU),
constancy) 2% ≥ 5MU 2% ≥ 5MU
Dosimetry Electron MU linearity (output 2% ≥ 5MU 2% ≥ 5MU 2% ≥ 5MU
constancy)
Dosimetry X-ray output constancy vs dose 2% 2% 2%
rate
Dosimetry X-ray output constancy vs 1% 1% 1%
gantry angle
Dosimetry Electron output constancy vs 1% 1% 1%
gantry angle
Dosimetry Electron and X-ray off-axis 1% 1% 1%
factor constancy vs gantry
angle
Dosimetry Arc mode (expected MU, 1% 1% 1%
degrees)
Dosimetry TBI/TSET mode Functional Functional Functional
Dosimetry PDD or TMR and OAF 1% (TBI) or 1 mm 1% (TBI) or 1 mm 1% (TBI) or 1 mm
constancy PDD shift (TSET) PDD shift (TSET) PDD shift (TSET)
Dosimetry TBI/TSET output calibration 2% 2% 2%
Dosimetry TBI/TSET accessories 2% 2% 2%
Mechanical Collimator rotation isocenter 1 mm 1 mm 1 mm
Mechanical Gantry rotation isocenter 1 mm 1 mm 1 mm
Mechanical Couch rotation isocenter 1 mm 1 mm 1 mm
Mechanical Electron applicator interlocks Functional Functional Functional
Mechanical Coincidence of radiation and 2 mm 2 mm 1 mm
mechanical isocenter
Mechanical Table top sag 2 mm 2 mm 2 mm
Mechanical Table angle 1° 1° 1°
Mechanical Table travel maximum range 2 mm 2 mm 2 mm
Mechanical Stereotactic accessories, locks, NA NA Functional
etc.
Safety Follow manufacturer’s test Functional Functional Functional
procedures
18 S. Sharma

Table 2.5 Acceptance testing of remote afterloading brachytherapy

Functional performance
Console functions Main power, battery power, source on/off, door open/close, etc.
Source control Source dwell time and source retraction at the end of preset time, unplanned interruption, or
emergency shutoff
Battery voltage Adequacy of battery voltage under load conditions and functional performance under battery
power
Timer Timer accuracy and end-time effects
Decay correction Accuracy of computer-calculated decay corrections
Multichannel Proper source sequencing and channel selection
indexer
Backup systems Proper functioning during simulated power failures or air pressure losses (for pneumatically
driven devices)
Radiation detectors Proper functioning as specified
Facility check and survey
Door interlocks Source retracts when the door is opened; the unit does not start until the door is closed and
the interlock is reset
Radiation warning Proper functioning to indicate radiation on/off condition
lights
Patient viewing and Proper functioning of closed-­circuit TV and the intercommunication system
communication
Radiation survey Exposure rates outside the radiation facility should meet the nuclear regulatory commission
regulations and the leakage radiation rates around the unit should be acceptable
Source calibration and transport
Check of source Leak testing, calibration, transport to the applicators, autoradiograph of simulated source
specifications positions, and isodose distribution to determine dose anisotropy

Table 2.6 Periodic test recommended by ESTRO for quality assurance for brachytherapy machines
Minimum requirements
Description Test frequency Action level
Safety systems
Warning lights Daily/3 month –
Room monitor Daily/3 month –
Communication equipment Daily/3 month –
Emergency stop 3 month –
Treatment interrupt 3 month –
Door interlock 3 month –
Power loss 3 month –
Applicator and catheter attachment 6 month –
Obstructed catheter 3 month –
Integrity of transfer tubes and applicator 3 month –
Timer termination Daily –
Contamination test Annual –
Leaking radiation Annual –
Emergency equipment (forceps, emergency safe, survey meter) Daily/3 month –
Practising emergency situations Annual –
Hand crank functioning Annual –
Hand-held monitor 3 month/annual
Physical parameters
Source calibration Source exchange >5%
Source position Daily/3 month >2 mm
Length of treatment tubes Annual >1 mm
Irradiation timer Annual > 1%
Date, time, and source strength in treatment unit Daily –
Transit time effect Annual –
2 Practical Aspects of QA in LINAC and Brachytherapy 19

ware with respect to standard decay table of the 2. Quality assurance of medical accelerators. AAPM Task
Group 142 report. Med Phys. 2009;36(9):4197–212.
source. 3. Glasgow GP, Bourland JD, Grigsby PW. A report of
AAPM task group no. 41 remote afterloading technol-
ogy. New York: AAPM; 1993.
References 4. Holt JG. AAPM Report No. 41: remote afterloading
technology. Med Phys. 1993;20(6):1761.
5. European Society For Therapeutic Radiology
1. Das IJ, Cheng CW, Watts RJ, Ahnesjö A, Gibbons J,
And Oncology. Quality assurance in radiotherapy.
Li XA, et al. Accelerator beam data commissioning
Radiother Oncol. 1995;35:61–73.
equipment and procedures: report of the TG-106 of
the Therapy Physics Committee of the AAPM. Med
Phys. 2008;35(9):4186–215.
 Radiation Dosimetry
3
Seema Sharma

3.1 Radiation Dosimeter not have dose and dose rate dependence, directional
dependence, energy response dependence, and it
Radiation dosimeter is a device that measures should have high spatial resolution. An ideal dosim-
directly or indirectly exposure, kerma, absorbed eter that satisfies all the above characteristics does
dose or equivalent dose, or related quantities of not exist. The refore type of radiation dosimeter that
ionizing radiation. The dosimetry system con- must be used, varies with measuring requirements
sists of dosimeter and its reader. of the measuring situation [1].
The radiation dosimeter must have at least one Different types of radiation measuring instru-
physical property that is a function of the mea- ments consider different physical events that can
sured dosimetric quantity and can be used for be utilized to make measurements. Different
radiation dosimetry with proper calibration. physical events that are commonly applied in
Ideal dosimeters are characterized by good accu- radiotherapy dosimetric equipments are summa-
racy, precision, linearity. Ideal dosimeters should rized below [2] (Fig. 3.1).

Fig. 3.1 Physical events

used for radiation Physical events used for radiation measurement
measurement

Ionisation Film Luminescence Semiconductor Gel

S. Sharma (*)
Department of Radiation Oncology, AIIMS,
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 21

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_3
22 S. Sharma

3.2 Ionization The wall of the thimble chamber should be air

equivalent, i.e., graphite (carbon), Bakelite,
3.2.1 Free Air Ionization Chamber [3] ­plastic with inside coating of graphite, or con-
ducting mixture of graphite and Bakelite. Exact
Free air ionization chamber is the primary stan- air equivalent material (atomic number same as
dard for measuring exposure for superficial and air) is not possible thus difference in atomic num-
orthovoltage (X-rays up to 300 Kv) (Fig. 3.2). ber is accounted in its calibration factor.
Free air ionization chamber cannot be used for The volume of air contained in air cavity is the
high energy photon, due to difficulty in maintain- sensitive volume of chamber. The thimble cavity
ing the electronic equilibrium in the collecting contains air and air can pass on through a small
volume. Therefore it can be used for superficial hole in the side of the chamber. For the measure-
and orthovoltage. ment with thimble chamber the temperature and
Free air ionization chamber is delicate and pressure of the air inside the cavity should be
bulky, therefore cannot be used for routine mea- same as the surrounding to maintain the
surements. They can be used in standardizing equilibrium.
laboratories for calibration of chambers used for Thimble chamber is a secondary dosimeter
low energy. and has to be calibrated against the free air ion
chamber or standard cavity chamber.

3.2.2 Thimble Chamber

3.2.3 Farmer Chamber
The wall of thimble chamber is like a sewing
thimble; therefore it is called as thimble chamber The original Farmer chamber was developed by
(Fig. 3.3). FT Farmer in 1955 (Figs. 3.4 and 3.5).
By compressing the air required for electronic Framer chambers are the most commonly
equilibrium its dimensions can be reduced. Air used ion chambers, for the calibration of radia-
volume required for electronic equilibrium can tion therapy beams. Farmer type chamber is also
be replaced by small air cavity with solid air known as cylindrical or thimble ionization
equivalent wall. chamber.

High voltage

Secondary
electron

collimated
beam
measuring reference volume
electrode

Fig. 3.2 Showing the schematic diagram of free air ion chamber
3 Radiation Dosimetry 23

Fig. 3.3 Showing the

Air shell Solid air shell
schematic diagram of
thimble chamber

Air cavity

Air cavity

Thimble wall
Insulator

Central
Air cavity electrode

Central Outer
PTCFE Insulator Graphite electrode electrode

Aluminium

Dural
~ 300 V

Fig. 3.4 Showing the schematic diagram of Farmer chamber

Fig. 3.5 Farmer

chamber
24 S. Sharma

An ionization chamber consists of a gas filled 1. Extrapolation chamber:

cavity with a central collecting electrode sur- (a) Extrapolation chamber was designed by
rounded by a conductive outer wall. A high qual- Failla in 1937. Extrapolation chamber is
ity insulator separates the wall and collecting used for measuring surface dose or build-
electrode to reduce the leakage current when ­up dose in a phantom (Fig. 3.6).
polarizing voltage is applied to the chamber. To (b) The beam enters through a thin foil win-
further reduce the chamber leakage the chamber dow that is carbon coated from inside to
also contains a guard electrode. form the upper electrode.
So many commercially available Farmer (c) The lower or the collecting electrode is a
chambers are available, they are similar in overall small coin shaped region surrounded by a
design but differ in composition of the wall mate- guard ring and is connected to an
rial and central electrode. electrometer.
The cavity of the chamber is vented to out- (d) The electrode spacing can be varied accu-
side. The measurement with open air ionization rately by a micrometer screw.
chamber requires temperature and pressure cor- (e) By measuring the ionization per unit vol-
rection to account for the change in the mass of ume as a function of electrode spacing,
the air in the chamber volume, which changes one can estimate the incident dose by
with ­ surrounding temperature and pressure. extrapolating the ionization curve to zero
Farmer type chamber has 0.6 cc nominal cavity electrode spacing.
volume. 2. Parallel plate (plane-parallel) chamber:
Parallel plate chamber is similar to extrapola-
tion chambers except that they have a fixed
3.2.4  arallel Plate Ionization
P electrode spacing (1–2 mm).
Chamber (a) Parallel plate chamber has two plane
walls, one serving as entry window (polar-
Parallel plate chambers have two electrodes in izing electrode) and the other as back wall
the shape of flat plates parallel to each other. The acting as collecting electrode (Fig. 3.7).
air gap between two electrodes constitutes the (b) Usually the window is foil or 0.01–0.03 mm
sensitive volume. thick Mylar, polystyrene, which allow mea-
There are two kinds of parallel plate cham- surement practically at the surface of the
bers: (A) the extrapolation chamber with variable phantom. Collecting electrode consists of a
volume, (B) the parallel plate chamber with fixed block of conducting plastic or non-con-
volume. ducting material with graphite coating.

Collecting
electrode Incident
radiation Thin foil
Guard upper electrode
ring

Three
micrometers
To
electrometer

Backscattering
material

Fig. 3.6 Showing the schematic diagram of extrapolation chamber

3 Radiation Dosimetry 25

Entrance window Direction of HT electrode

radiation

Air Volume
1-2 mm

Guard ring
Insulator Collector electrode

Fig. 3.7 Showing the schematic diagram of parallel plate chamber

Source Holder

Air volume

Electrode

Well insert

Source

50 mm
Spacer

To electrometer

Fig. 3.8 Showing the schematic diagram of well type chamber

(c) It also contains guard ring system. The width dardization of brachytherapy sources.
of the guard ring is sufficiently large to pre- Re-entrant ion chamber is filled with air and
vent electrons scattered by the side and back communicate to the outside air through a vent
walls of the chamber from affecting the ion- hole. Usually calibrated in terms of reference
ization in the ion collecting volume. air kerma rate.

3.2.5 Well Type Chamber

3.3 Film
Sources used in brachytherapy are low air
kerma rate sources that require chambers of 3.3.1 Radiographic Film
sufficient volume (about 245 cc) for adequate
sensitivity. This much active volume is large Radiographic X-ray film (unexposed) consists of,
enough to generate sufficient ionization cur- thin plastic film coated both sides with a radiation
rent which can be measured with electrometer sensitive emulsion (silver bromide, AgBr grains
(Fig. 3.8). suspended in gelatin).
Well type chambers are re-entrant cham- On the exposure (ionization of AgBr grains
bers ideally suited for calibration and stan- take place), loosely bound electrons are freed,
26 S. Sharma

Fig. 3.9 Showing the cross section of radiographic Protective layer (gelatin)
film Emulsion (silver halide)
Adhesive

Plastic base

Adhesive
Emulsion (silver halide)
Protective layer (gelatin)

Fig. 3.10 (a) Showing

the cross section of
radiochromic film (b) Matte Polyester, 100 µm
exposed radiochromic
film Active Layer, ~28 µm

Matte Polyester, 100 µm

a b

these electrons aggregate around impurities and active layer polymerizes, it becomes partially
form negative charge. This negative charge opaque in proportion to the incident dose (Fig. 3.10).
attracts Ag+ion leaving behind neutral metallic The polymer absorbs lights and transmission
silver and forms the latent image in the film. of light through the film can be measured with
Latent image becomes visible (film blackening) suitable densitometer.
after film processing (Fig. 3.9). Radiochromic film is self-developing; there-
Film gives excellent 2D spatial resolution, but fore requires no processing or developing. No
useful dose range of film is limited. need of dark room and cassettes.
Response of the film depends on so many fac- Radiochromic film has very high spatial reso-
tors, which are difficult to control, i.e., consistent lution and dose rate independence.
film processing, dark room facility. Radiochromic film does not require process-
Film blackening (light transmission) can be ing but complete polymerization reaction takes
measured in terms of optical density (OD) with time approximately 24 h, therefore it results in
densitometers. Optical density is converted to delay between irradiation and readout.
absorbed dose via calibration.
Hunter and Driffield (H&D) curve is used to
relate the exposure or dose to optical density. 3.3.3 Luminescence

Some materials upon absorption of radiation

3.3.2 Radiochromic Film [4] retain part of absorbed energy in metastable
states. This energy is subsequently released in the
Radiochromic film consists of polyester (Mylar) base form of ultraviolet, visible, or infrared light, the
which is nearly a tissue equivalent composition. phenomenon is called luminescence.
Radiochromic film contains a special dye that is Two types of luminescence, (i) fluorescence
polymerized upon exposure to radiation. As the and (ii) phosphorescence, are known, which
depend on the time delay between stimulation
3 Radiation Dosimetry 27

and emission of light. Fluorescence occurs eter is called the thermoluminescent dosimeter
with time delay of 10−8 s, phosphorescence (TLD).
occurs with time delay of more than 10−8 s or If the exciting agent is light, the phenome-
with the suitable excitation with heat or light non is known as optically stimulated lumines-
(Fig. 3.11). cence (OSL) and the dosimeter is called as
Incident ionizing radiation creates the electron optically stimulated luminescent dosimeter
hole pair in the crystal structure. The liberated (OSLD).
electron is moved (promoted) to the conduction
and migrates to the electron trap. At the same
time hole migrates (along the valence band) to a 3.3.4 Thermoluminescent
hole trap. Dosimeter (TLD)
Energy in the form of heat for TLD or light for
OSLD is given to electron and hole to escape Many TLD materials are available, the widely used
from their traps. Finally electron hole pair com- TLD materials are LiF:Mg, Cu, P, LiF:Mg, Ti,
bines at the luminescent center and releases CaSO4:Dy, etc. The elements mentioned after the
(emits) light. TLD are the dopants or impurities. The dopants are
If the exciting agent is heat, the phenomenon used to create the metastable states or traps.
is called the thermoluminescence and the dosim- TLDs are available at various shapes and sizes
such as powder, chip, rods, disc, and ribbon

Conduction band

Heat

Electron trap
Electron
trap

Impurity level Impurity level

Visible light

Hole trap
Hole trap
recombination center

x-ray Valence band

Fig. 3.11 Showing the schematic diagram of luminescence

 28 S. Sharma

depending upon their dosimetric requirement portional to temperature. This gives rise to dis-
(Fig. 3.12). tinct glow peaks (Fig. 3.13).
When TLD is heated, because traps differ in
depth, probability of escaping from trap is pro-

a b

Fig. 3.12 (a) TLD chip (b) TLD badge for personal monitoring

50 3.3.5 Optically Stimulated

LiF: Mg.Cu, Si Luminescent Dosimeter
40 LiF: Mg.Cu, P (OSLD)
TL Intensity (a.u.)

30 Al2O3:C is sensitive OSLD and used for personal

dosimetry. Light emission is achieved by
20 ­stimulating crystal with light of constant inten-
sity such as LASER, LEDs, lamps, etc.
10 Emission wavelength is characteristic of
OSL material, and the rate of luminescence is
0 proportional to stimulating LASER light
350 400 450 500 550 600 intensity.
Temperature (K) The OSL reader integrates the photons over
the period of stimulation. The stimulating light
Fig. 3.13 Showing the glow curve
must be prevented from being interpreted as sig-
nal. OSLD reading is fast (1 s).
Before reusing OSLD, bleaching treatment
Heating (up to certain temperature) a TLD with light from a halogen lamp, fluorescent
gives a glow curve, which is a graph of intensity lamp, or green LED has to be performed. This
as a function of temperature. empties most trap centers and prepares OSLD
For reuse of TLD annealing has to be done, by for reuse.
which traps are emptied. For annealing process TLD Deep traps are not emptied in this process may
has to be heated at 400 °C (approximately) for 1 h. be supplemented with thermal annealing.
3 Radiation Dosimetry 29

3.4 Semiconductor MOSFET, holes flow between drain and source.

Whereas N-channel MOSFET, source, and drain
3.4.1 Diode Detector are composed of N-type semiconductor and gate
is composed of P-type semiconductor. In
Diode dosimeter is comprised of p-n junction N-channel MOSFET, electrons flow between
diode, which is a junction of P-type and N-type drain and source. Only P-channel MOSFET is
semiconductor. N-type semiconductors are elec- used in radiation measurement.
tron donors, P-type semiconductors are electron The voltage necessary to initiate current flow
acceptors. Some known impurities (called between source and drain is known as threshold volt-
dopent) are added to the semiconductors to make age. When MOSFET device is exposed to radiation,
P-type of N-type diodes (Fig. 3.14). electron hole pairs are generated. The difference in
When radiation incident upon the sensitive voltage shift before and after the exposure can be
volume or depletion layer of the diode it liberates measured and can be correlated with the dose.
ions (either electron or holes). Electrons or holes Unlike TLD/OSLD, the traps cannot be emp-
will start to move in sensitive volume due to tied (annealing), therefore MOSFET can be used
strong electric field and induce current. This cur- for permanent dose record (Fig. 3.15).
rent can be measured by electrometer and further
can be calibrated for absorbed dose.
3.5 Gel Dosimeter

3.4.2 MOSFET Detector Gel dosimeters are composed of radiation sensi-

tive chemical, when exposed to ionizing radiation
MOSFET (Metal Oxide Semiconductor Field they undergo fundamental changes in their prop-
Effect Transistor) consists of three leads, drain, erty, which is proportional to the absorbed dose.
source, and gate. Gel dosimeters are 3D dosimeters and can be
P-channel MOSFET, source, and drain are molded in any shape and size (Fig. 3.16).
composed of P-type semiconductor and gate is Gel dosimeters are mainly two types: (1)
composed of N-type semiconductor. In P-channel Fricke gel and (2) Polymer gel.

a Incident Radiation b

−Va+
− +
Electron Hole
Anode Cathode
P − + n

− +

x=x2 x =0− x =0− x =x1

Ln W Lp

Electrometer
Radiation Current

Fig. 3.14 (a) Showing the workflow of diode. (b) Commercially available diodes
30 S. Sharma

G
a b
S D D

P+ P+

B
N P channel
G
S

B Depletion Mode

Fig. 3.15 (a) Showing the P-type MOSFET. (b) Commercially available MOSFET

Fig. 3.16 Showing the gel dosimeter [image taken

(with permission) from, Natanasabapathi G, et al.
(2015) verifying dynamic planning in gamma knife
radiosurgery using gel dosimetry. IFMBE
Proceedings 2015, vol51. springer, Cham]

bers for charge of photoelectrons, Compton elec-

References trons and auger electrons. Radiat Prot Dosim.
2008;130(4):410–8.
1. Seco J, Clasie B, Partridge M. Review on the char- 3. Kron T, Lehmann J, Greer PB. Dosimetry of ionis-
acteristics of radiation detectors for dosimetry and ing radiation in modern radiation oncology. Phys Med
imaging. Phys Med Biol. 2014;59(20):R303–47. Biol. 2016;61(14):R167–205.
2. Takata N, Begum A. Corrections to air kerma and 4. Devic S, Tomic N, Lewis D. Reference radiochromic
exposure measured with free air ionisation cham- film dosimetry: review of technical aspects. Phys
Med. 2016;32(4):541–56.
 Radiation Protection Practical
Aspects 4
Ashish Binjola

4.1 Introduction Natural background radiation and the

sources of man-made radiation: we are contin-
Ionizing radiation has a number of applications uously exposed to low level of natural radia-
that make our life better. In the field of medi- tion which is known as background radiation.
cine, ionizing radiation is used in the diagnosis The source of background radiation is radioac-
of disease as well as for the treatment. In the tive elements present in rocks (terrestrial radia-
petroleum industry radioisotopes are used for tion), cosmic radiation from the space (the
imaging oil and gas pipelines defects to avoid level of cosmic radiation increases with alti-
oil or gas leakage known as nondestructive tude), etc., K40 and C12 which are the radio-
analysis. Well logging, using radioactive isotopes present inside our body also add to
sources is useful in determining whether a our background radiation.
drilled well has certain minerals, petroleum, Medical exposure, exposure due to consumer
gas, or other valuable substances. In the field items, occupational exposure, etc., which may
of agriculture, radiation helps to produce high add to our radiation dose, are the sources of man-­
yield seeds for better productivity as well as made radiation.
for preserving the food items for a longer dura-
tion (food irradiation can delay sprouting and
avoid pests in certain crops). Radiation is used 4.2 Important Organizations
for sterilization of healthcare items and equip- Pertaining to Radiation
ment, can help to make polymers (radiation Safety
polymerization), and have numerous research
applications as well in different fields of sci- (a) International Commission on Radiological
ence, etc. But, on the flip side radiation can Protection (ICRP), Ottawa, Canada.
pose serious health hazards, if not used in a (b) International Atomic Energy Agency
planned and proper manner as advised by (IAEA), Vienna, Austria
national and international regulators and advi- (c) National Council on Radiation Protection
sory bodies providing regulations and guide- and Measurements, Washington, DC, USA
lines for correct use of radiation. (d) The International Labour Organization
(ILO), Geneva, Switzerland
(e) International Commission on Radiation
A. Binjola (*)
Units and Measurements, USA
Department of Radiation Oncology, AIIMS, (f) World Health Organization (WHO), Geneva,
New Delhi, India Switzerland
© Springer Nature Singapore Pte Ltd. 2020 31
S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_4
32 A. Binjola

4.3  asic Quantities and Units

B 1 rad = 1 cGy
in Radiation Safety
Equivalent Dose The equivalent dose (H) is a
Radioactivity Radioactivity is defined as spon-
quantity which is actually derived from the
taneous emission of radiation from the nucleus
quantity absorbed dose, but it also takes care of
of an unstable atom, and in this process, the
the type of radiation as well as its energy for the
unstable atom disintegrates into comparatively
difference of biological effects (harm to the
stable atom (either a different atom or the same
body tissues). For example, a high energy alpha
atom in lower energy state). The number of dis-
particle or proton beam will have more harm
integration the radioactive substance undergoes
compared to photon beam due to its higher
per unit time is known as activity (A) of the
LET/specific ionization. Equivalent dose is
radioactive substance.
defined as:
The SI unit of activity is Bq (1 disintegration H = D × WR
per second) and the special unit is Ci where WR is known as the radiation weighting
(1 Ci = 3.7 × 1010 Bq). factor. WR takes care of differences in biological
effectiveness of different types of ionizing
Exposure The quantity exposure (X) is defined radiation.
as the quotient of the absolute value of total The unit of equivalent dose is Joule/Kg and its
charge of the ions of either sign produced by the special name is Sievert (Sv). Another special unit of
radiation (dQ) in the air by the mass of the air equivalent dose is rem (radiation equivalent man).
(dm), when all the charges produced in the air are
completely stopped in air, i.e., the state of elec- 1 rem = 1 cSv
tronic equilibrium exists. Table 4.1 represents the recommended values
dQ of WR by ICRP 103
X =
dm
Effective Dose Effective dose (E) is another
The quantity exposure is defined only for X- very important quantity for radiation protection.
and gamma rays and it is only a measure of ion- Different tissues in the human body have a differ-
ization of air. ent probability for stochastic effects of radiation.
The exposure is measured in R (Roentgen). Effective dose incorporates tissue weighting fac-
1 R = 2.58 × 10−4 Coulomb / kg tor for differences in biological effectiveness of

Radiation Absorbed Dose The quantity Table 4.1 Radiation weighting factor for different types
absorbed dose, D, is defined as the quotient of of radiation
dE / dm , where d E is the mean energy imparted Recommended values of radiation weighting factor by
to matter of mass dm by the ionizing radiation. ICRP 103 [1]
Radiation type WR
dE X-rays, gamma rays 1
D= photons, electrons, and
dm
muons
The SI unit of the absorbed dose is joule/Kg. Protons and charged pi 2
The special name of the unit of absorbed dose is ions
Gy. Alpha particles, fission 20
fragments, and heavy
1 Gy = 1 Joule / Kg ions
Neutrons A continuous function of
Another special unit of equivalent dose is rad neutron energy, maximum
(radiation absorbed dose). value 20 at 1 MeV
4 Radiation Protection Practical Aspects 33

Table 4.2 Tissue weighting factor for various tissues below the acceptable limit. There are three basic
Recommended values of tissue weighting factor by principles of radiation protection which helps to
ICRP 103 [1] attain our goal of radiation safety:
Tissue WT
Bone marrow, breast, colon, lung, 0.12 for each 1. Justification of practice: No practice causing
stomach
radiation exposure shall be adopted unless its
Gonads 0.08
Bladder, liver, tissue, thyroid 0.04 for each
introduction produces a net positive benefit.
Bone surface, brain, salivary gland, 0.01 for each 2. The principle of optimization: All exposures
skin should be kept as low as reasonably achiev-
Remainder tissues 0.12 able (ALARA) taking into account social
and economic factors. In radiation applica-
tions, doses can be minimized (as low as
different tissues for ionizing radiation. Effective
reasonably achievable) by adopting the
dose (E), for a given tissue, is defined as
principle of time, distance, and shielding
E = H × WT explained as:
As per ICRP 103 different values of tissue (a) Time: The radiation dose to an individual
weighting factors are given as follows (Table 4.2): is directly proportional to the time spent
The effective dose has the same unit as the in the radiation field. Hence by reducing
equivalent dose. the time spent in the radiation field, one
For radiation safety purposes, as a rule of can reduce the radiation dose. Previous
thumb, we may take (only for X- and gamma practice with dummy sources (dry run)
rays): can reduce time spent while handling
actual radiation sources, thereby reducing
1 R = 1rad = 1rem radiation dose.
Or (b) Distance: Ionizing radiation follows
1 R = 0.01Gy = 0.01Sv inverse square law; it means that doubling
the distance will reduce the dose to one
Or
fourth. Use of long forceps for handling
1mR = 10 µ Gy = 10 …Sv the radioactive sources may reduce the
dose drastically. We should never touch
Radiation Effects Ionizing radiation is known the radioactive source, as it may deliver a
to have deleterious effects on human health. very high dose because of very less
These effects can be classified as (1) distance.
Deterministic effects or tissue reactions having a (c) Shielding: Shielding attenuates the radia-
threshold limit of the dose after which these tion beam intensity and so reduces the
effects are certain to occur and severity of effect dose. Shielding of radiation installations/
increases with dose, e.g., radiation-induced cata- sources is optimized to reduce the doses
racts, fibrosis of lungs, skin erythema, radiation- to the personnel and public below the pre-
induced nausea, temporary or permanent scribed limit by the regulator.
sterility, etc. (2) Stochastic effects having no (i) Shielding for alpha particles: Alpha
threshold limit and the probability of effect particles are positively charged
increases with dose, e.g., radiation-induced car- helium nuclei and can be stopped
cinogenesis and hereditary effects. relatively easily. High energy alpha
particles have very limited penetra-
Radiation Protection In any sort of radiation tion of few mm in tissues. 1.0–2.0 cm
applications, the goal of radiation protection is to of the plastic sheet will be adequate
avoid deterministic effects completely and to to shield against the beam of high
minimize the probability of stochastic effects energy alpha particles.
34 A. Binjola

(ii) Shielding for beta particles: Beta Table 4.3 Dose limit as per International Commission of
particles are negatively or positively Radiation Protection
charged particles (electrons or posi- Type of limit Occupational Trainee Public
trons) emitted from the nucleus of a Stochastic 20 mSv per 6 mSv in 1 mSv
effects: year, averaged a year in a
radioactive atom. Beta particles have
effective over a defined averaged year
a larger depth of penetration com- dose limits period of over
pared to alpha particles; high energy (whole 5 years, with no 5 years
electrons from the Linac also have body) single year
exceeding
the same properties.
50 mSv
(iii) Sources emitting beta particles can Annual equivalent dose in (parts of the body)
be shielded effectively using a dou- The lens of 20 mSv per 50 mSv in 15 mSv
ble layer shielding container. The the eye year, averaged a year in a
inner layer of the container is made over a defined year
up of low atomic number material to period of
5 years, with no
absorb the beta particles with mini- single year
mum production of Bremsstrahlung exceeding
X-rays. Outer layer is made up of 50 mSv
high atomic number material to Skin 500 mSv in a 150 mSv 50 mSv
year in a year in a
attenuate the X-rays produced by year
electron interactions as well as asso- Hands and 500 mSv in a 150 mSv 50 mSv
ciated gamma rays followed by feet year in a year in a
emission of a beta particle. year
(iv) For patient treatment, high energy Effective dose limits for the pregnant radiation worker:
electrons in a Linac can be shielded The dose to the surface of the abdomen is 2 mSv for the
entire gestation period and the dose limit to the fetus is
(partly) using lead cutout over the 1 mSv
distal end of electron applicator
1
{Lead Thickness ( mm ) = × be shielded using hydrogenous mate-
2
Energy of electron ( MeV ) + 1}. rial, e.g., polythene slabs. Concrete
is also an effective shielding material
Concrete shielding used to shield for neutron shielding for high energy
X-ray photons in Linac bunker can Linac installation. Borated poly-
provide adequate protection for per- thene doors can be used at the
sonnel and public. entrance of the Linac installation to
(v) Shielding for X- /gamma rays: absorb high energy neutrons, if
X-rays and gamma rays follow expo- required.
nential attenuation and it cannot be (d) Dose limits: Dose to individuals shall not
completely blocked. However, by exceed recommended limits stipulated by
using proper shielding, we can bring ICRP and National regulatory body.
the radiation level around the source
well below the safe limits. Lead, Dose limits for radiation workers and mem-
steel, tungsten alloy, steel, etc. can bers of the public are provided in the International
effectively attenuate the X or Commission of Radiation Protection (ICRP) 60
gamma-ray beam. Concrete can be and 103 reports (Table 4.3). Later in the year
used as an effective shielding mate- 2011, ICRP has modified limit for the lens of the
rial for radiotherapy installations. eye to 20 mSv per year (ICRP 118) from
(vi) Shielding for neutrons: Neutrons are 150 mSv per year from its previous recommen-
electrically neutral particles and can dations [1–3].
4 Radiation Protection Practical Aspects 35

4.4 Transport of Radioactive tained in the package, specific activity of the

Material material, etc.
Every package should meet general packaging
We shall take serious precautions in the transpor- requirements of robustness (drop test, water
tation of radioactive material. Transport of radio- immersion test, stake test, fire test, etc.) depending
active materials should never harm person, on the package type as well as specific additional
property, and environment from the effects of requirements for fissile material. The package
radiation during the transport of radioactive should be properly marked and labeled. United
material. Personnel involved in the transport of Nations number and proper shipment name should
radioactive materials shall have the personnel be written. Trem (Transport Emergency) card and
radiation monitors to monitor their doses and placards should also be added along with transport
their radiation doses shall be kept within dose index (TI). Apart from this, consignor’s declara-
limits prescribed by the national regulatory tion should also be provided.
authority. Total number of personnel involved Types of radioactive packages for the purpose
and exposure to them shall be kept as low as rea- of transport can be broadly classified as:
sonably achievable. If there is an emergency situ-
ation, a written emergency action plan shall be 1. Excepted packages
ready and implemented to protect person, prop- 2. Industrial packages
erty, and environment. People who are involved 3. Fissile packages
in transport shall be well trained for handling 4. Type A (Fig. 4.1)
radioactive material and to handle an emergency 5. Type B
situation. 6. Type C package
The protection can be achieved by:
In the radiation oncology department, mainly
1. Containment of radioactive content. two isotopes are used for the radiotherapy:
2. Control of external radiation levels.
3. Prevention of the criticality. 1. Co-60 radioisotopes for teletherapy and
4. Prevention of damage caused by heat 2. Ir-192 or Co – 60 sources for brachytherapy.
These sources shall be transported only after
Classification of packages is based upon obtaining the required permission from the
shielding integrity of the packaging and the quan- regulatory authority. Brachytherapy sources
tity of radioactive material and also on whether (approximately up to 10 Ci) can be trans-
the material is fissile or not, total activity con- ported in type “A” package. In the transport of

Fig. 4.1 The packaging

of radioactive material
for transport, the type
“A” package
36 A. Binjola

teletherapy source, there is an involvement of (b) Airborne contamination monitor: This

higher activity (up to 12,000 Ci) and shall be monitor measures the concentration of
transported in Type “B” package. radiation particle which is ingested or
(a) The radioactive material comes under UN deposited in the lung. They give an alarm
class 7 of dangerous goods. in presence of airborne contamination.
(b) Transport index (TI): The transport index This monitor is often connected to an
is defined as the maximum level of radia- integrated safety system in a manner that
tion in mrem/h at 1 m from the surface of personnel are prevented from entering the
the package. area when airborne contamination is more
than the safe limit.
(c) Personnel exit monitor (PEM): Personnel
4.5 Equipment Required exit monitors are used to monitor workers
for Radiation Safety in a contaminated controlled area. This
monitor can sense the level of exposure or
Radiation protection instruments are essential in contamination in the surface of the work-
ensuring and evaluating the radiation dose which er’s body or the clothing they generally
is being received by the individual. These measure alpha beta or gamma contamina-
­instruments can be either installed and fixed or, tion. The PEM can be in the form of a
portable and handheld. hand monitor, cloth frisk probe, or whole
body monitor.
1. Installed equipment: Installed equipment is 2. Survey meters: These instruments are com-
important in ensuring the general radiation pact and handheld. Survey meters are useful
hazard in a particular area of interest; this to survey a particular area or to check an
includes area radiation monitor, airborne object or person in detail for the presence of
particulate monitors, personnel exit moni- radiation (Figs. 4.3 and 4.4). Survey meter
tor, etc. generally measures the dose rate of beta and
(a) Area radiation monitor: Area radiation gamma rays in mR/h or mSv/h Survey
monitor will measure usually gamma rays meters can be gas based or solid state detec-
which have a significant radiation level tor based. In radiotherapy for linear acceler-
beyond a threshold. Use of gamma zone ator, being a source of pulsed X-rays, ion
monitors is a regulatory requirement for
telecobalt and brachytherapy installations
(Fig. 4.2). It can avoid unintentional and
accidental exposure. Gamma zone moni-
tors are GM based or solid state detector
based.

Fig. 4.2 Area gamma monitor installed for brachyther-

apy installation Fig. 4.3 Neutron survey meter
4 Radiation Protection Practical Aspects 37

4.6.1 Management of Radioactive

Waste

1. Delay and decay: This technique is used for

short-lived radioisotopes; the reason is to
decrease the risk when released to the envi-
ronment. Short-lived radioisotopes having
half-life less than one month can be disposed
after approximately delay of 10 half-lives, till
then waste is stored in a properly shielded and
ventilated room. After 10 half-lives, its activ-
ity is being assessed and if its activity is below
the prescribed limit, it can be disposed as low
activity radioactive waste.
2. Dilute and disperse: This technique is used
Fig. 4.4 Pressurized ion chamber based survey meter for waste with very less activity (less than 50
KBq), which is diluted and then released to
the environment which will not be harmful
chamber based survey meters are generally anymore.
used. For better sensitivity, air is pressurized 3. Concentrate and contain: This technique is
in some ion chambers based survey meters. used for high activity and long half-life radio-
For gamma rays sources (telecobalt and active waste, which should be kept safely in
brachytherapy) GM based survey meters can isolation away from the reach of normal pub-
also be used. For high energy linear accel- lic below the ground (burial). E.g., Disused
erators having energies above 10 MV, neu- teletherapy source.
tron survey meter is also a useful instrument
for measuring neutron dose rate. Neutron
survey meters are generally He3 or BF3 based 4.6.2 Radioactive Waste
gas detectors. on the Basis of the Physical
Form

4.6 Radioactive Waste Disposal 1. Liquid waste

2. Solid waste
In radiotherapy only shielded sources are used, 3. Gaseous waste
but in nuclear medicine, open sources (liquid
sources, as well as gaseous sources which may Liquid and gaseous wastes can be classified
arise from volatile liquid sources) might be used. on the basis of the content of radioactivity while
Disused sources as well as anything (gloves, solid waste can be classified on the basis of dose
syringes, vials, patient secretions, etc.) which rate on the package surface. Liquid waste of cat-
contains radioactive contamination should be egory III and IV need to be shielded properly, and
termed as radioactive waste and should be man- category V required shielding and cooling during
aged as per the regulations provided by the com- handling storage treatment and disposal.
petent regulatory authority.
Safe management of radioactive waste is 1. Liquid waste: liquid wastes are contaminated
important to ensure safety to the people and the water and effluent waste arising from the
environment. If radioactive waste is not managed chemical processing and decontamination
properly it may harm living beings. solutions, solvents, blood or body fluids,
38 A. Binjola

discharged liquid and radiopharmaceutical, meter. Installation should be surveyed from

wound and oral discharge, urine, etc. time to time to assess the safety of the areas
2. Solid waste: solid waste is formed from tissue around the installations.
paper, plastics, contaminated materials, pro- • All the equipment and sources used in radio-
tective wears, equipment, and materials used therapy shall conform to the applicable stan-
on radioactive material. dards of the International Electrotechnical
3. Gaseous waste: Management of gaseous is Commission (IEC) and International Standard
very important because once it is released in Organization (ISO) and shall be type approved
air nobody can control it. It may pose the fol- by the national regulator.
lowing three kinds of hazards: • Acceptance testing of all radiation generating
(a) Direct irradiation hazard equipment shall be performed as per the
(b) Ingestion hazard guidelines of international bodies (ISO, IEC,
(c) Inhalation hazard IAEA, etc.) along with guidelines of the
national regulatory body.
• Radiotherapy equipment must be properly
4.6.3 Quality Assurance commissioned and QA must be done for
and Radiation Safety equipment including all major and minor
in Radiotherapy accessories.
• Equipment can be used for patient treatment
Quality Assurance is concerned with all those pro- only after obtaining the due license from the
cedures that ensure consistency of the medical pre-
scription and the safe fulfillment of that prescription
national regulatory body.
as regards dose to the target volume, together with • All the sources and equipment shall be used
minimal dose to normal tissue, minimal exposure for the intended purpose only according to the
of personnel, and adequate patient monitoring terms and condition of license by the
aimed at determining the end result of treatment.—
WHO (1998)
regulator.
• Quality assurance of all the equipment should
In radiation therapy linear accelerators, which be done in stipulated frequency as per the
are the sources of megavoltage electrons and national and international guidelines.
X-rays, are the most commonly used teletherapy • Proper radiation symbol and warnings should
equipment. Radioactive sources Ir -192 and Co- be pasted outside the treatment room and
60 are most common for high dose rate brachy- entry to the controlled area shall be restricted.
therapy. Apart from that, radiotherapy simulator, • The symbol for radiation hazard and X-ray
CT simulator, and cone beam CT are the KV hazard is shown in Figs. 4.5 and 4.6
X-ray sources. • Adequate staffing should be done and radia-
tion safety training should be provided by the
• Any equipment used for the diagnosis or treat- Radiological Safety Officer to all concerned,
ment of patients should be type approved by time to time.
the national regulator.
• Equipment shall be installed in the properly
designed shielded bunker/room duly approved
by the national regulatory body.
• Radiation installations shall be surveyed
with the help of a calibrated ion chamber/
GM counter. If the Linac is having high
energy photons and electrons (greater than
10 MV), it should also be surveyed for neu-
trons using a calibrated neutron survey Fig. 4.5 The symbol for radiation hazard
4 Radiation Protection Practical Aspects 39

ation dose, overexposure to the patient, public

or personnel, etc. shall be reported to the regu-
latory body.
• Records and documentation of all the safety
procedures, QA, personnel doses, etc. should
be properly maintained.

Fig. 4.6 The symbol for X-ray hazard References

1. The 2007 recommendations of the international com-
• All the radiation professional and workers mission on radiological protection. ICRP publication
must be provided personnel with radiation 103. Ann ICRP. 2007;37(2–4):1–332.
2. Stewart FA, Akleyev AV, Hauer-Jensen M, Hendry
monitors to record their doses.
JH, Kleiman NJ, Macvittie TJ, et al. ICRP publication
• Radiation emergency plan shall be clearly 118: ICRP statement on tissue reactions and early and
written and pasted on the machine console and late effects of radiation in normal tissues and organs-
time to time mock drill of emergency plan -threshold doses for tissue reactions in a radiation pro-
tection context. Ann ICRP. 2012;41(1–2):1–322.
should be performed.
3. 1990 recommendations of the international com-
• Any accident involving radiation, loss of mission on radiological protection. Ann ICRP.
radioactive source, mis-administration of radi- 1991;21(1–3):1–201.
 Beam Modifying Devices
5
Supriya Mallick and Goura K. Rath

Beam modifying devices are devices which when 5.1 Shielding

kept in path of beam produces a desirable modifi-
cation in the special distribution of the beam. The aims of the shielding in radiation treatment
Types of beam modification are as follows: are as follows:

• Shielding: To eliminate radiation dose to 1. Protecting critical organs by shielding them

selected part of the treatment area 2. Avoiding irradiation of surrounding normal
• Compensation: A compensator attenuates the tissue
beam based on the irregular contour of the patient 3. Helps in better matching of adjacent fields
• Wedge filtration: Used to produce a desired
spacial tilt in isodose curves The characteristics of the ideal shielding
• Flattening: Where the spatial distribution of material are as follows:
the natural beam is made uniform in a LINAC
by reducing the central exposure rate relative 1. High atomic number
to the periphery 2. High-density material
3. Easily available and inexpensive
Types of beam modification devices are as
follows: The choice material for shielding depends on
the type of radiation beam being used.
• Field blocking and shaping devices: Shielding
blocks, Custom blocks, Jaws, Multileaf
collimators. 5.1.1 Gamma and X-Ray Shielding
–– Compensators
–– Beam spoilers • High-density materials—more effective for
–– Wedge filters blocking or reducing the intensity of radiation
–– Beam flattening filters • Lead (due to its high atomic number) is par-
–– Bolus ticularly well suited for shielding of gamma
–– Breast cone rays and X-rays
–– Penumbra trimmers • Practically thickness of lead between 4.5–5
half-value layers results in 5% or less of pri-
S. Mallick (*) · G. K. Rath mary beam transmission (Table 5.1)
Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 41

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_5
42 S. Mallick and G. K. Rath

• The relationship holds true, only for monoen- • Also called: Wood’s metal, Bendalloy,
ergetic X-ray beams Pewtalloy, and MCP
• Contents: 50% bismuth, 26.7% lead, 13.3%
tin, and 10% cadmium by weight
5.1.2 Neutron Shielding • The melting point is 70 °C (158 °F)—main
advantage of Cerrobend, can be easily cast
• Materials composed of low atomic number into any shape
elements are preferable for shielding neutrons • Density 9.4 g/cm3 at 20 °C
as they have a higher probability of forming • 1.21 times thicker blocks are necessary if
cross-sections (through elastic scattering), to made of Cerrobend when compared to lead to
interact with the neutrons. get the same attenuation
• Hydrogen and hydrogen-based materials are • Usual thickness is 7.5 cm
usually used. Thus compounds with a high • Shielding blocks types:
concentration of hydrogen atoms (such as –– When central area is blocked it is called
water) form efficient neutron barrier. Another positive blocks.
advantage is that it is relatively inexpensive. –– When periphery of field is blocked it is
• However, low-density materials can emit called negative blocks.
gamma rays when blocking neutrons, thus –– Divergent block—when the edge of the
high energy material may be added to block block follows divergence of beam. It helps
gamma rays. So neutron shielding is most in reducing transmission penumbrae.
effective when a combination of both high and • Blocks are kept at a distance of 20 cm from
low atomic number elements is used. skin in telecobalt machine, while in kilovolt-
age radiation lead blocks are placed directly
The number of HVL (n) required is given by
the following expression:
Table 5.1 Lead thickness required for shielding for dif-
ferent beam energies
5.2 Custom Blocks [1] Beam energy Required lead thickness (cm)
4 MV 6.0
• Used to block of the part of the field and is 6 MV 6.5
customly made using Lipowitz metal or 10 MV 7.0
Cerrobend (Fig. 5.1) Co60(1.25 MeV) 5.0

Cerrobend

Tin
13%

Bismuth Lead
50% 27%

Cadmium
10%

Fig. 5.1 Cerrobend composition and structure

5 Beam Modifying Devices 43

over the patient. This is because secondary • Transmission via leaves—less than 2%.
radiation is major part in low voltage radiation • Interleaf transmission—less than 3%.
and benefit of shielding will be lost if distance • Transmission via jaws—less than 1%
between shield and patient is larger. Table 5.2 • Transmission via Cerrobend blocks—less
summarizes various materials that can be used than 3.5%
for making blocks.
MLCs can also be used as dynamic wedges and
electronic compensators in conformal planning
5.3 Independent Jaws Disadvantages:

• Used to block of the part of the field without • MLCs have jagged boundary, hence matching
changing the position of the isocenter. of various fields may create underdosing and
• Thickness is made usually of 10 HVL overdosing
• Can be used for beam splitting where the • Island blocking is not possible with MLCs
beam is blocked off at the central axis to avoid alone
the divergence. • MLCs have a larger physical penumbra than
• Disadvantage: Use of independent jaws can blocks and thus blocks are better for shielding
result in the shift of the isodose curves which of critical structures, near the field
may alter the dose distribution.

5.4.1 Types
5.4 Multileaf Collimator
• Single focus leaves MLC—rounded at end
Multileaf collimators consist of paired colli- • Double focus leaves MLC—leaf and leaf size
mating leaves(usually 40 pairs of leaves) hav- match with beam
ing a width of 1 cm or less (projected at the • The main aim of both designs is to reduce
isocenter) [2]. It is usually constructed with a penumbrae
tongue and groove design to allow easy and
fast interleaf movement, while reducing radi- MLCs with leaf widths between about 2 and
ation transmission via the leaves. One of the 5 mm are called mini MLCS, while micro MLCs
disadvantages of this design is underdosing have leaf width below about 2 mm.
(10–25%)in the region of the tongue
(Fig. 5.2).
5.5 Compensators
• Usually is made of a tungsten alloy.
• Thickness in the range of 7.5–8 cm Compensator is a beam modifying device which
• Usual speed—2.5 cm per second is used to compensate for tissue inhomogenicity,
so that the skin surface contours are evened out,
Primary X-ray transmission: while retaining the skin-sparing advantage.

Table 5.2 Composition of various materials that can be used for making blocks
Alloy Melting point Bismuth (%) Lead (%) Tin (%) Indium (%) Cadmium (%)
Rose’s metal 98 °C (208 °F) 50 25 25 – –
Cerrosafe 74 °C (165 °F) 42.5 37.7 11.3 – 8.5
Wood’s metal 70 °C (158 °F) 50 26.7 13.3 – 10
Field’s metal 62 °C (144 °F) 32.5 – 16.5 51 –
Cerrolow 136 58 °C (136 °F) 49 18 12 21 –
44 S. Mallick and G. K. Rath

5.5.1 Types Systems used for design of 3D compensators:

The compensators may be two-dimensional or 1. Moiré camera—consists of a specially

three-dimensional: designed camera mounted on simulator which

• In 2D compensators (Fig. 5.3), thickness var-

ies, along a one dimension only. It can be
made of lead, lucite, or aluminum.
• Three-dimensional compensators (Fig. 5.4)
measure tissue deficits in both transverse and
longitudinal cross-sections.

Tongue and Groove Design MLC

Fig. 5.2 Tongue and groove design of multileaf

collimator Fig. 5.3 Showing 2D compensator

Fig. 5.4 Making of a 3D compensator

5 Beam Modifying Devices 45

makes a topographical map of the patients

surface which is used to produce 3D

Y
compensators
2. Magnetic digitizers—consist of a magnetic
sensor in a handheld stylus which scans the
patient body which is used to make 3D
compensators
3. Computed tomography based images can also
be used to make 3D compensators using com-
pensator designing systems

X
Electronic compensators: MLCs are used to
produce effect similar to a compensator in a
Fig. 5.5 Schematic representation of wedge
LINAC.

5.6 Wedge Filters

Wedge filter is a beam modifying device, which

when placed in the path of the beam produces a
progressive decrease in intensity across the beam,
which results in tilting the isodose curves in the
desired direction.
Fig. 5.6 Wedges used for telecobalt and LINACS
• Material: Wedge filters can be made of lead,
brass, tungsten, and steel • Figure 5.6 shows wedges used for telecobalt
• Usually kept at a distance of about 15 cm from and LINACS
the patient skin • Usual wedge angles are 15°, 30°, 45°, 60°
• Wedge transmission factor (WTF) = Dose
Types of wedge systems: with the wedge divided by dose without the
wedge and is measured along the central axis
–– Individualized wedge—Used in cobalt of the beam
machines • Wedge isodose angle (θ in Fig. 5.7) is the
–– Universal wedge complement of the angle through which the
–– Dynamic wedges isodose curve is tilted with respect to the cen-
–– Enhanced dynamic wedge tral axis of the beam
–– Virtual wedges • Hinge angle is the angle between central axis
of 2 beams. The wedge angle chosen depends
on the “hinge angle”(φ) (Fig. 5.7).
• The width (W) of the wedge is fixed and is the • The two factors on that help in choosing
important dimension (Fig. 5.5) wedge angle are:
• It is possible to use the same wedge in fields –– The hinge angle.
with lesser lengths or breadths –– The wedge separation.
• The commonly available wedge systems for
telecobalt machine are: Motorized wedges are 60° wedges mounted in
–– 6 W ( × 15) the treatment head and are moved into the field
–– 8 W ( × 15) for part of the time to create the wedge beam pro-
–– 10 W ( × 15). file desired
46 S. Mallick and G. K. Rath

Dynamic Enhanced Wedge Creates desired • The main advantage is that wedge factor is not
wedge beam profile effects by moving jaws in needed when virtual wedge is used
and out of the field

5.7 Bolus
Pseudo Wedge Also called poor man wedge
• Bolus is a tissue equivalent material used to
• Pseudo wedge is created by opening of small reduce the depth of the maximum dose (Dmax)
field in large field or to bring up the surface dose
• E.g., Small field gives 1/2rd dose while larger • Also known as “build-up bolus.”
delivers the rest 1/2 of the dose • Use of bolus:
• Used in olden days when asymmetrical jaws –– In megavoltage radiation bolus—bring up
opening was not possible and no planning the buildup zone (reduce the skin-sparing
TPS were available. effect) in treating superficial lesions.
–– It can act as a compensator for missing tis-
Virtual Wedge sue or irregular surface.
• Commonly used materials are: (Fig. 5.8)
• In virtual wedge dosimetry is produced by –– Cotton soaked with water(water acts as
movement of collimators using a treatment bolus)
planning system –– Paraffin wax
–– Mix- D
–– Lincolnshire bolus: made up of 83 percent
sugar and 13 percent magnesium carbonate
–– Spiers bolus: made up of 60 percent rice
flour and 40 percent calcium carbonate
• Properties of an ideal bolus:
q
–– Ideal bolus must have similar electron den-
sity to the tissue
–– Must be pliable to conform to surface to
make it uniform
–– Ideal bolus must have similar absorption
Fig. 5.7 Schematic representation of wedge angle and and scattering properties as that of tissue
hinge angle –– Specific gravity must be around 1.02–1.03

Fig. 5.8 Common bolus used in radiotherapy

5 Beam Modifying Devices 47

• The thickness of the bolus varies according to Penumbra width of a beam depends on the fol-
the energy of the radiation. lowing factors:
–– CO-60: 2–3 mm
–– 6 MV Photons: 7–8 mm • Diameter of the source—Penumbra width
–– 10 MV Photons: 12–14 mm increases as source diameter increases
–– 25 MV Photons: 18–20 mm • Source to skin distance—Penumbra width
increases as source to skin distance increases
• Depth
5.7.1 Uses of Bolus • Source to diaphragm distance—inversely
related
1. Increase skin dose
2. Even out the surface Penumbra trimmers are made of heavy metal
3. If deep structures need to be spared to bring and placed in the path of the beam so as to attenu-
up isodose ate the beam in the penumbra region there by
reducing penumbra.
Other measures to reduce penumbra
5.8 Breast Cone
• Increase the source to diaphragm distance,
A beam directing device used in tangential field’s which leads to a reduction in geometric
therapy in breast cancer radiotherapy. penumbra
Advantages: • Placing secondary blocks close to the patient
• Directs beam to the central axis of the area of (e.g., 15–20 cm)
interest
• Helps position, the patient and ensure correct
position at SSD 5.10 Flattening Filters
• Provides compensation for tissue
inhomogeneity Used in linear accelerators—reduces the central
• Provides effective shielding of lungs below exposure rate relative to that of the edge of the
breast tissue beam.
Thus it is shaped as a cone with the thickest
part is in the center.
5.9 Penumbra Trimmers Materials used to make flattening filters: cop-
per or brass.
The penumbra is the region of steep dose rate
decrease (between the points at which the 20%
and 80% isodose curves) at the edge of radiation 5.11  eam Modifying Devices
B
beam for Electron Beams
Types
• A primary collimator is provided close to
• Geometrical penumbra; due to the size of the source—defines the maximum field size.
source with larger geometrical penumbra for • Electron cone— used to provide collimation
larger source size for the electron beam.
• Transmission penumbra; occurs due to the • A secondary collimator, near the patient
beam emerging from the edges of blocks or defines the treatment field.
collimators • Lead cutouts—used for electron field shaping.
48 S. Mallick and G. K. Rath

• Lead cutouts—placed directly on the skin. References

• A tissue equivalent material (wax/dental
acrylic) is coated over the lead shield to pro- 1. Johnson JM, Gerbi BJ. Quality control of custom
block making in radiation therapy. Med Dosim.
tect against backscatter electrons. 1989;14(3):199–202.
• Examples of areas where coating with wax or 2. Zhang X, Ye P, Zhang H. Development and perfor-
dental acrylic is required are the buccal mance evaluation of a high-speed multileaf collima-
mucosa and eye lids. tor. J Appl Clin Med Phys. 2017;18(1):96–106.
 Simulators
6
Bhanu Prasad Venkatesulu

6.1 2D Simulators 6.2 3D Simulators

Conventional two dimensional X-ray simulator is 6.2.1  T Simulators (https://www.

C
used to image the tumor in two dimensions for healthcare.siemens.com/
determination of the field borders, location and to magnetic-resonance-imaging/
define the target. Milliampere (mA) and kilo volt- magnetom-world/hot-topics/
age (kV) can be modulated to impact the noise mri-in-radiation-therapy/
and attenuation of the tissue. Skin markers play articles-and-case-studies)
an important role in the reproducibility of treat-
ment, ensuring accurate targeting and proper In 3D CT simulator, a dedicated CT is used for
dose applied to tissue. The target is defined in radiotherapy treatment simulation. CT scanner
relation to anatomic landmarks; the extent of acquires volumetric CT-scan and the
fields is driven by knowledge of anatomy and by CT-simulation software provides virtual repre-
disease pathways. Physical examination, palpa- sentation of the geometric capabilities of a treat-
tion, and physical measurements of the patient ment machine. The components of a CT simulator
are important in 2D planning. Dose distribution include X-ray tube, large bore CT scanner with
information limited to single plane of major sig- an opening of up to 85 cm, detectors systems,
nificance in order to cover the target. Energy collimators and attenuator, flat patients couch,
selection is defined by the AP and lateral separa- laser. The main difference between a diagnostic
tion of the patient. Typically if the AP separation CT machine and a radiation CT simulator is the
>16 cm better to use four fields rather than two wide bore and flat couch to ensure reproducibil-
fields (http://www.myradiotherapy.com/general/ ity between the imaging position and treatment
ct_planning/Simulators/radiotherapy_simula- position. Patient positioning and immobilization
tors). forms the cornerstone for accurate beam delivery.
During the CT simulation radiopaque markers
are kept on the skin adjacent to the region of
interest and it forms the patient isocenter and this
is used to define the tumor isocenter during treat-
ment planning. 3D radiation therapy simulation
allows graphic display of the 3D anatomy of
B. P. Venkatesulu (*) tumor and normal tissues. The CT images pro-
Department of Radiation Oncology, MD Anderson vide excellent soft tissue contrast which helps in
Cancer Center, Houston, TX, USA

© Springer Nature Singapore Pte Ltd. 2020 49

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_6
50 B. P. Venkatesulu

Fig. 6.3 MRI simulator

Fig. 6.1 Shows a radiotherapy CT simulator that has a
wide bore of 85 cm with a flat couch which is similar to
the treatment couch patient positioning to CT simulation and treat-
ment, flat bed couch with the necessary radiofre-
quency coil, MRI compatible immobilization
devices, placement of RF coils must not alter
patient position. MRI simulators are being
increasingly used for brachytherapy procedures
in gynecological malignancies, adaptive replan-
ning in head and neck malignancies (https://
www.healthcare.siemens.com/magnetic-reso-
nance-imaging/magnetom-world/hot-topics/mri-
in-radiation-therapy/articles-and-case-studies).

6.2.3 PET-CT Simulators

Fig. 6.2 Shows a patient of carcinoma rectum being PET is done after CT imaging in the same patient
imaged with a thermoplastic immobilization device position. About 6–7 bed positions are planned in
the 3-D acquisition mode for scanning the entire
patient with 5–7-min acquisition at each bed posi-
better tumor localization in comparison to con- tion. The PET-CT can scan a maximum length of
ventional simulator. Electron density information 145 cm for one patient [1]. The field of view of
from CT images is used in the calculation of dose PET scan is 58.5 cm. It has a spatial resolution of
inhomogeneity. Figure 6.1 shows a CT simulator, 5 mm, and the sections are post processed to a
and Fig. 6.2 shows a patient with carcinoma rec- thickness of 2.4 mm. The PET/CT scanners allow
tum being simulated. for functional/metabolic evaluation of the tumors.

6.2.2 MRI Simulators Reference

MRI simulators has superior soft tissue contrast 1. Brianzoni E, et al. Radiotherapy planning: PET/
CT scanner performances in the definition of gross
compared to CT, functional imaging are additive tumour volume and clinical target volume. Eur J Nucl
tools for MR simulation (Fig. 6.3). The basic Med Mol Imaging. 2005;32(12):1392–9.
requirements include patient set-up, identical
 Telecobalt
7
Rony Benson and Supriya Mallick

7.1 History • Half-life (1/2 t, i.e., the time required for the
activity of the source to half) of Co-60 is
• Began to be used from 1950s [medical linear 5.27 years. For practical purposes it is consid-
accelerator was developed in the 1970s]. ered harmless and inactive after 10 half lives.
• The first patient—1951, at Victoria Hospital in Thus, Co-60 should be stored safely for
London. approximately 53 years.
• First cobalt-60 teletherapy unit in India— • The source is cylindrical in shape and has
Cancer Institute, Adyar in 1956. diameter of 2 cm.
• The source activity is generally between 5,000
and 15,000 Curie.
7.2 Isotope [1] • A source with an activity of less than 3000 Ci
is replaced with a new one; this is necessary
• Naturally occurring cobalt is a hard, bluish-­ after 5–7 years of use.
gray, easily breakable metal with 27 protons, • Source is in form of disc-stacked one over
32 neutrons, and 27 electrons. another and doubly encapsulated.
• Nonradioactive cobalt—imparts blue color to • Capsule prevents leakage and absorbs beta rays.
glass and ceramics. • The source-isocenter distance (SAD) is
• The isotope Co-60 was discovered at 80–100 cm.
California Berkeley University in 1930. • Rotational movement of the gantry is motor-
• Co-60 is now produced commercially in ized and controlled in two directions continu-
nuclear reactors [by bombarding Co-59 with ously; its rotation speed can be adjusted. The
neutrons]. gantry can rotate by 360°.
• Decay of Co-60 starts with a b-decay, fol- • BRIT—Board for Radiation Isotope
lowed by two gamma emissions with energies Technology—[Mumbai]—provides sources
of 1.17321 and 1.33247 MV (Fig. 7.1). for Co-60, Ir-192.

R. Benson (*) · S. Mallick

Department of Medical Oncology, RCC,
Thiruvanthapuram, India

© Springer Nature Singapore Pte Ltd. 2020 51

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_7
52 R. Benson and S. Mallick

Beta 0.31 MeV

Absorbed by capsule

60
Co 60
27 Ni
28

Stable

Gamma 1.17 MeV Gamma 1.33 Mev

Used for Treatment

Fig. 7.1 Decay of Cobalt-60

Fig. 7.2 Treatment

Tungsten
head of telecobalt
machine
Lead

Air Cylender

Collimator

Source
Tungsten Block

7.3 Machine Details 7.4 Source Stuck

The cobalt source (orange) is situated in a Steps to follow in case of accidental source stuck
drawer and surrounded by lead. When the device
is in the resting position, the source is protected • Turn the gantry to opposite direction and ask
by layers of enriched uranium. The source is the patient to come out (if patient can move).
then pushed by a pneumatic system to the treat- • Go in with T-rod.
ment position. Figure 7.2 shows schematic rep- • Get out of the patient first.
resentation of treatment head of telecobalt • The head has the source indicator rod attached
machine with the source drawer and moves with the
source that indicates beam is ON.
• Activity = 9,000–12,000 curie. • The external T-rod (Fig. 7.3) should be fitted
• Primary barrier—130 cm of concrete. with this indicator rod to push the source to
• Secondary barrier—65–70 cm of concrete. the OFF position.
7 Telecobalt 53

• Insert T-rod to yellow zone indicated on it

[T-rod—red—danger, yellow—safe].
• If source does not go inside, lock the room and
inform Radiation Safety Officer, hospital
director, licensee, and then inform AERB.

7.5 Miscellaneous Points [2]

• Indian Cobalt Machines—Bhabhatron and

Bhabhatron-II.
• Advantages over LINAC—less expensive,
less service cost, less QA.
• Disadvantages—has large part as penum-
brae, MLC and asymmetric jaw not available
in most of machines, does not produce elec-
tron. Figure 7.4 compares telecobalt with
LINAC.

Fig. 7.3 T-rod with colors indicating source position

Telecobalt LINAC
Cost Less Expensive More Expensive
Electricity Requires higher electrical energy
requirements
Energy 1.25 MeV Gamma X ray 4-21 MV
Multiple energies availbale
Field Max 35*35 cm 40*40 cm
MIN 5*5 cm 0.5*0.5 cm
Penumbra 1.5 cm Less 6 mv=7 mm
Source size Cylinder of diameter 2 cm, height 3 cm Virtual -3-5 mm[focal spot]

PPD at 10 cm 55% 6 mv-67%

Shields 5HVL= Lead 5.5 cm 4 mv-6 cm Lead
6 mv-6.5 cm Lead
Barrier Primary-130 cm Prim barrier 250-300 cm depending on
Secondary-70 cm energy

Max dose rate Fixed reduces with time Variable, higher dose rate available for
SBRT in HDR mode
Wedges Individualized wedges Universal wedges
Collimator 3% 0.5%
transmission
Maintenence cost Less More
Radiation hazard Always on Only when machine is on
Electrons Only Gamma rays available for Availability of electrons
treatment
Source change Need for source change after 5-8 No need to change source
years But life span low

Fig. 7.4 Comparison of telecobalt and linear accelerator

54 R. Benson and S. Mallick

References 2. Ravichandran R. Has the time come for doing away

with Cobalt-60 teletherapy for cancer treatments. J
Med Phys. 2009;34(2):63–5.
1. Ravichandran R. Radioactive Cobalt-60 teletherapy
machine: estimates of personnel dose in mock emer-
gency in patient release during “source stuck situa-
tion”. J Med Phys. 2017;42(2):96–8.
 Gamma Knife
8
Renu Madan

Gamma Knife radiosurgery is also known as ste- 8.1 I ndication of Gamma Knife
reotactic radiosurgery (SRS). It is a form of radi- Surgery
ation used to treat brain disorders. In contrast to
its name, the procedure does not involve any sur- 8.1.1 Single-Fraction GK SRS
gical intervention. It is a type of radiation deliv-
ery where multiple ionizing beams are focused 1. Tumor size: 3–4 cm
and make them to collide at one point. Each radi- 2. Distance from optic nerve at-least 2 mm
ation beam is consisted of low radiation dose to 3. Maximum lesions that can be treated in single
spare normal tissues, whereas higher dose is session: 30
delivered to kill the tumor cells. Currently, it is a
worldwide accepted method to treat variety of
intracranial tumors, vascular and functional brain 8.1.2  ultiple Fraction GK SRS
M
disorder. (Extend System)

History Concept of SRS was first given by a 1. Tumor size >4 cm

neurosurgeon, Lars Leksell in 1951. It was in 2. Tumor too close to optic apparatus
1951 in Stockholm, Sweden, when first patient
was treated by SRS. Initially X-rays were used
however later they were replaced by radioac- 8.2  valuation of Gamma Knife/
E
tive cobalt. This was defined as Gamma Knife Various Models
stereotactic radiosurgery (GKS). First Gamma
Knife machine in USA was used in the There have been multiple developments in the
University of Pittsburgh in 1987 [1]. In Asia, design and technique of the Gamma Knife
First Gamma Knife center was opened in Japan machine.
in 1990 in the University of Tokyo Hospital [2] Four important models have been described:
and ASAN Medical Center (Seoul, South model U or A (Introduced in 1967), model C
Korea) [3]. (Introduced in 1999), Perfexion (Introduced in
2006), and Gamma Knife Icon (Developed in
2016). The first model (U/A) had 201 cobalt 60
sources, arranged in hemispheric configuration.
R. Madan (*) There were issues with loading and re-loading of
Department of Radiotherapy and Oncology, Post
Graduate Institute of Medical Education and the sources in this model. To overcome this,
Research, Chandigarh, India ­models B, C, and 4C were designed in which

© Springer Nature Singapore Pte Ltd. 2020 55

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_8
56 R. Madan

sources were arranged in circular configuration. 3. Better radiation protection

Automatic positioning system (APS) was devel- 4. Fully automated treatment system
oped with the model C which was replaced by 5. More comfortable to patient
patient positioning system (PPS) in the newest
model Perfexion (Elekta Instruments AB, Instead of 201 cobalt-60 sources in earlier,
Stockholm, Sweden). Perfexion has 192 cobalt-60 sources that are
Availability of computer based robotic device arranged in a cylindrical arrangement (in contrast
for GKS has significantly improved the safety to previous hemispheric arrangement). These
and clinical implementation of SRS. The APS is sources are arranged in five concentric rings and
a robotic computer controlled device in model C source to focus distance for each ring ranges
and 4C (Elekta instrument AB) which was used from 377 to 433 mm. In contrast to the primary
for automatic change of the patient head position and secondary collimators in the earlier models,
when it is fixed in the stereotactic frame. Whereas there is only single integrated and permanent
in PPS, entire couch moves with the patient head tungsten collimator array ring (120 mm). It has
that provides more comfort to the patient. It gives opening of three different diameters of the colli-
extremely high precision of 0.1 mm in any co-­ mator (4, 8, and 16 mm) which are divided into
ordination direction. Use of this system has eight sectors. These sectors move independently
resulted in high selectivity and conformity indi- around the edge of the device [6]. Each sector
ces leading to delivery of more homogenous dose consists of 24 sources and 72 collimators (24 for
to the target area and avoiding excessive dose to 4, 8, and 16 mm each). By servo-controlled motor
normal brain parenchyma [4]. system, these can be moved independently in five
Model C was designed in 1999 and first positions:
installed in 2003 in the University of Pittsburgh.
This model had advanced techniques consisting 1. Home position with standby system
of automatic positioning system (APS) and 2. 4 mm collimator position
robotic engineering that obviated the need of 3. 8 mm collimator position
manually adjusting the co-ordinates in a multiple 4. 16 mm collimator position, and
isocenter plan. Subsequently this spares time on 5. Sector off position, i.e., blocking all the beams
each patient and also increases accuracy [5]. An
updated version of model 4C was introduced in During the treatment these collimators can be
2005 and was first installed in the University of used or blocked individually. A single isocenter
Pittsburgh. It provides better radiation protection can also be generated by use of different sized
for patients and staffs, as sources are always in collimator (composite or hybrid shot). This
the off position during patient shifting from one method increases conformity and selectivity and
to another position, transition into new stereotac- is more effective when tumor is located near criti-
tic co-ordinates, or during emergency cal structures. This can also be used to treat larger
interruption. tumors and are otherwise out of the tumor size
criteria [6]. Larger tumor (three times as com-
pared to previous models) can be treated on LKG
8.3  eksell Gamma Knife (LGK)
L Perfexion. Additional advantage is modification
Perfexion of the dose distribution by blocking some colli-
mators also known as dynamic shaping. If critical
This relatively newer model of LGK has similar organs are delineated as named as “risk volume,”
radiation dose profile as per the previous units. the system automatically blocks the beam pass-
However the additional properties are: ing through it [7]. Automatic off and on of beam
during transition of co-ordinates from one iso-
1. Better dosimetry center to other also reduces the treatment time
2. Deep intracranial access [8]. Thus multiple tumors, i.e., brain metastasis,
8 Gamma Knife 57

can be treated and reapplication of the stereotac- nuclear reactions are involved in MRI, this
tic frame can be avoided. More advanced tech- modality also is a source of errors which may
nology with Perfexion can also be used to treat result in distortion artifacts and affect image
previously non-accessible tumors, i.e., skull base quality and accuracy. Thus, MRI alone for radio-
tumors, maxillofacial tumors, and tumors of cer- surgical treatment planning should be used with
vical spine. caution. Although resolution is poor with CT, it is
Perfexion couch has mechanical accuracy of less prone for the localization errors. It also has
<0.05 mm. APS in model C has been replaced by the potential of better visualization of bony struc-
patient positioning system (PPS) in Perfexion. tures, it can be used to correct the distortion arti-
Entire couch moves according to the stereotactic fact created by MRI. The automated algorithm of
co-ordinates (in contrast to only head in previous the Leksell GammaPlan allows easy co-­
models) providing more comfort to the patient. registration of MRI and CT. The fused images
Fully automated system reduces the work-load can provide better information as compared to
on staff and decreases human errors. the individual modality. Thus, routine acquisition
of CT scans and use of fused images is a more
practical option even if the tumor is well identi-
8.4 Technique fied on MRI.

The first and foremost part of the treatment plan- 1.5 T MRI is a valid option due to easy avail-
ning with Gamma Knife is placement of stereo- ability as compared to 3T MRI. The standard
tactic frame. Pre-operative images should be MRI imaging protocol used for SRS treatment
reviewed in advance to decide for the optimal planning of brain tumors consists of conventional
frame place strategy. After frame placement, spin-echo (SE) or turbo spin-echo (TSE) T1- and
patient is enclosed in PPS by an adapter (attached T2-weighted sequences, post contrast
to the standard stereotactic Leksell G frame with T1-weighted SE or TSE, and T1-weighted
three clips). Here, patient can be attached in three sequences with magnetization transfer contrast.
different gamma angles of 70°, 90°, or 110° that The use of contrast media is recommended [9].
reflect neck flexion or extension. The gamma Contrast-enhanced perfusion weighted imaging
angle is the only parameter that requires manual (PWI), dynamic contrast-enhanced MRI (DCE-­
set up. MRI), MR spectroscopy (MRS), diffusion-­
Frame adaptor is used to attach the frame on weighted imaging (DWI), and diffusion tensor
the table. Every attempt has to be made to avoid imaging (DTI) are also used sometimes.
the collision of the frame base plate and patient Incorporation of functional MRI techniques into
head with the collimator helmet. Position of the routine morphological imaging protocols
patient head with respect to the treatment plan is may identify the extent and biologically the most
checked by frame cap. Position of the frame can aggressive parts of the target [10].
be changed on the base ring using the ear bars. Bi-plane angiograms are used along with MRI
Fiducials should be placed on the frame prior to to see AV malformations.
sending the patient to MRI unit.
Target Delineation For target delineation,
Neuro-imaging Protocol Imaging is one of the 1–1.5 mm slices are constructed. It is an impor-
most important parts of Gamma Knife treatment tant step to make a conformal plan. Delineation
planning. Contrast-enhanced magnetic resonance can be done using the LGPâ software (manual or
imaging (CEMRI) is the current standard of care. semiautomatic mode). Although experienced
MRI is considered as a standard modality for personnel can create conformal dose plan with-
radiosurgery as it provides excellent resolution out delineating the target, delineation of target
and allows ideal 3D localization of the soft tissue and critical structures allows for a better
or the targets. However as multiple complex ­assessment of the plan and various parameters
58 R. Madan

such as dose volume histograms for tumor and and sharp fall-off of the dose outside the target.
critical structures along with selectivity and con-Thus in case where multiple shots have to be used
formity indexes can be calculated. for the treatment of large or irregular shaped
tumor, one should always attempt to generate
Treatment Planning Several options are multiple shots that mimics the dose distribution
available for a conformal plan on Gamma of a single shot.
Knife. In model C, treatment planning can be The disadvantage of using multiple shots is an
done using robotic automatic patient position- overlapping of the isodose curves on the target.
ing system (APS mode), manual positioning This phenomenon is known as “normalization
(trunnion mode), or mixed treatment (some iso- effects” between the shots also known as hot
centers in APS mode and some in trunnion spot.
mode). Most of the users prefer shots and In GKS single or multiple isocenters of vari-
directly place them over the target. However, ous beam diameter can be used for the desired
inverse dose planning algorithm (WizardÒ) can coverage of the target. Total numbers of isocen-
also be used to create a plan which can be later ters depend on the size, shape, and location of the
optimized manually. target. Each isocenter has three stereotactic co-­
ordinates (X, Y, Z Cartesian co-ordinates) that
The best change in treatment planning with correspond to its location in the 3D space which
Perfexion is the generation of single isocenter by is defined by rigidly fixed stereotactic frame.
use of multiple different sized collimators. Once the APS treatment plan is generated, it
Multiple small collimators lead to better confor- can be directly transferred from the planning
mal planning. computer to control computer. Combination of
In this, a newer version of Leksell GammaPlan isocenters of same beam diameter (run) is then
PFX (LGP PFX) with Linux operating system is selected that matches the collimator helmet on
used. There are three approaches in treatment the gamma unit. Patient’s head frame is fixed
planning: into the APS which is moved to dock the posi-
tion. The precision of the docking position is
1. Use of classic combination of 4, 8, and 16 mm checked. This is followed by the clearance
collimators (shots) checks for all planned isocenters in which the
2. Composite combination of 4, 8, and 16 mm pins, posts, frame, or patient’s head should be
3. Sectors block to protect volume at risk-­ less than 12 mm away from the inner surface of
dynamic shaping. the collimator helmet. The clearance check is
done by moving the patient to the desired posi-
Typically multiple shots are used to treat the tions under APS manual control and also by
tumor. This is more helpful in case of irregular visual check of collision with the collimator
tumor to increase the conformity. However irreg- helmet. Once these tests are done, position
ular and large tumors are at increased risk of checks are made to see the positions of isocen-
developing postradiation complications because ters that use the same helmet. This is done by
the normal tissue may get the higher dose [11]. In moving the patient’s head to these positions
these cases, the prescribed dose can be decreased using APS manual control. It should be make
to reduce the risk of complication. However, sure that patient is comfortable in all head posi-
optimal target coverage should also be kept in the tion. After all the mandatory tests, radiotherapy
mind. is given to the patient.
In forward treatment planning, a single radia- The APS moves the patient to all planned
tion shot delivers the maximum dose to the tar- positions, one by one, until the isocenters using
get, i.e., large portion of higher isodose lines a that size collimator helmet are completed. Set up
small target area, leading to uniform high-dose of patient and co-ordinates of different iso-cen-
radiation to the target and a steep dose gradient tres is done on the control computer.
8 Gamma Knife 59

LGK Perfexion is a fully automatic machine. trol rate of >95% [12]. As compared to sur-
All aspects of the procedure are set automati- gery, GKS has a high rate of preservation of
cally, i.e., setting of the stereotactic co-ordinates facial nerve function and hearing [13].
and different sector positions that define size of Typically, a radiosurgery dose of 12–13 Gy at
the collimator to be used, adequate exposure the 50% isodose line leads to adequate tumor
time, and blockade of the beam to spare normal growth control and at this dose, temporary or
tissue. All the treatment data is then exported to permanent treatment related dysfunction of
the treatment console. The only thing which has the VII cranial nerve can be avoided in 99% of
to be adjusted manually is the positioning of the cases. The radiation dose in SRS to the cochlea
head in the docking device and couch adjustment should not exceed 4 Gy.
for the patient comfort. Around 95% of the SRS 2. Sellar tumors: Pituitary adenomas (PA) and
with Perfexion can be administered in a single craniopharyngiomas (CPH) are the most com-
run. During SRS patient can be communicated by mon tumors in the sellar-suprasellar region.
an audio-visual system, and the treatment can be Combined, they represent around 15% of all
interrupted at any time in case of emergency. intracranial tumors. PA arise from the anterior
pituitary gland, while CPH arise from epithe-
lial cells of Rathke’s pouch.
8.5 Quality Assurance Microsurgery is the gold standard for the
treatment. Surgical removal has various
Daily quality assurance is necessary to check the advantages including histopathological con-
proper functioning of the system according to firmation, immediate decompression of the
nuclear regulatory commission (NRC) guide- optic apparatus, and rapid reduction of the
lines. These guidelines include testing of radia- excessive hormonal secretion. However,
tion monitors, camera and console, door interlock, 3–4% of the patients develop severe morbidity
emergency interruption of the treatment button, after surgery (visual loss, ophthalmoplegia,
emergency removal of the patient, functioning of stroke) and less severe complications can be
helmet hoist to change the collimator helmet, and seen in 5–20% [14] Overall recurrence rate
checking of APS and PPS. A test run simulating after microsurgery ranges between 8% and
the treatment is performed to check the function- 57% (for both PA and CPH) [14]. Medical
ing of APS and PPS. treatment with dopamine agonists and soma-
tostatin analogue can also be used; however,
in a meta-analysis of 35 studies, hormonal
8.6 Common Indications, Target normalization was reported in 55% to 90%
Doses, and Dose to Critical while the tumor regression rate was from 20%
Structures to 80% [14]. Studies have shown that SRS is
the ideal treatment of PA if microsurgery and/
1. Acoustic neuroma (vestibular schwannoma): or medical treatment does not control tumor
There are two options for the treatment: growth or if there is any contraindication to
microsurgery and radiosurgery. Generally, these modalities. Good control of PA has been
surgical resection is recommended. However, reported after SRS, however results vary for
there has been increase in the number of endocrinopathies. Overall, GH and ACTH
patients undergoing SRS for acoustic neu- over secretion are better controlled as com-
roma. The main objective of GKS in VS is pared to prolactin [15].
growth control and at the same time preserv- For hormone secreting PA mean recom-
ing neurological functions, especially useful mended dose is 25 Gy while lower doses are
in those cases where the tumor is in close effective for nonsecreting PA (mean recom-
vicinity of cranial nerves. Large number of mended dose is 15 Gy). For CPHs, the mean
published reports have reported a tumor con- recommended dose is 9–12 Gy.
60 R. Madan

Recommended maximum dose to brain References

stem should not exceed 12 Gy.
Maximum tolerated dose for optic appara- 1. Lasak JM, Gorecki JP. The history of stereotactic
tus is 8 Gy but in some cases, a dose of 10 Gy radiosurgery and radiotherapy. Otolaryngol Clin N
Am. 2009;42(4):593–9.
is also accepted with a low risk of complica- 2. Otto S. History and present status of gamma
tions. However, volume receiving >10 Gy knife radiosurgery in Japan. Prog Neurol Surg.
should not exceed 9 mm3 2009;22:1–10.
3. Meningioma: The recommended dose for 3. Hwang S. History of Korean stereotactic and func-
tional neurosurgery. Neurosurgery. 2005;56(2):406–
non-benign meningiomas ranges from 14 to 9.. discussion 406–409
20 Gy. For smaller tumors a dose of 4. Régis J, Hayashi M, Porcheron D, Delsanti C,
18–20 Gy can be given. For tumors with a Muracciole X, Peragut JC. Impact of the model C and
volume of ~10 cm3, 15–16 Gy, and for larger automatic positioning system on gamma knife radio-
surgery: an evaluation in vestibular schwannomas. J
tumors, SRS dose is generally limited up to Neurosurg. 2002;97(5 Suppl):588–91.
14 Gy. 5. Kuo JS, Yu C, Giannotta SL, Petrovich Z, Apuzzo
4. Brain metastasis: The marginal dose of MLJ. The Leksell gamma knife model U versus
20–22 Gy at 50% isodose is used for the treat- model C: a quantitative comparison of radiosurgical
treatment parameters. Neurosurgery. 2004;55(1):168–
ment of brain metastasis and for trigeminal 72.. discussion 172–173
neuralgia, a dose of 85–90 Gy is associated 6. Lindquist C, Paddick I. The Leksell gamma knife
with adequate pain relief. Perfexion and comparisons with its predecessors.
Neurosurgery. 2007;61(3 Suppl):130–40.. discussion
140–41
7. Yomo S, Tamura M, Carron R, Porcheron D, Régis
8.7 Complications J. A quantitative comparison of radiosurgical treat-
ment parameters in vestibular schwannomas: the
The complications after radiation arise due to Leksell gamma knife Perfexion versus model
4C. Acta Neurochir. 2010;152(1):47–55.
exposure of normal tissue to radiation. Several 8. Régis J, Tamura M, Guillot C, Yomo S, Muraciolle
treatment parameters may affect the severity of X, Nagaje M, et al. Radiosurgery with the world’s
complications, i.e., dose, dose volume, dose first fully robotized Leksell gamma knife PerfeXion
rate, and tissue radiosensitivity. Thus all in clinical use: a 200-patient prospective, random-
ized, controlled comparison with the gamma knife
attempts should be made to minimize the radia- 4C. Neurosurgery. 2009;64(2):346–55.. discussion
tion dose to critical structures. Gamma Knife 355–356
surgery is generally a safe procedure. Few 9. Asao C, Korogi Y, Kitajima M, Hirai T, Baba Y,
patients can experience fatigue, headache, or Makino K, et al. Diffusion-weighted imaging of
radiation-induced brain injury for differentiation
nausea. from tumor recurrence. AJNR Am J Neuroradiol.
2005;26(6):1455–60.
Gamma Knife Icon Icon is the advanced ver- 10. Chen W, Silverman DHS, Delaloye S, Czernin J,
sion and the next generation of the Leksell tech- Kamdar N, Pope W, et al. 18F-FDOPA PET imag-
ing of brain tumors: comparison study with 18F-FDG
nology. It is an upgradation of LGK Perfexion PET and evaluation of diagnostic accuracy. J Nucl
and was introduced in 2016 (Elekta AB, Med Off Publ Soc Nucl Med. 2006;47(6):904–11.
Stockholm, Sweden). The most important bene- 11. Ganz JC, Reda WA, Abdelkarim K. Gamma knife
fit of icon is that patients can be treated without surgery of large meningiomas: early response to treat-
ment. Acta Neurochir. 2009;151(1):1–8.
head frame. A custom face mask is used in con- 12. Bakkouri WE, Kania RE, Guichard J-P, Lot G,
trast to the more rigid head frame. The technique Herman P, Huy PTB. Conservative management of
and procedures of radiation are similar as the 386 cases of unilateral vestibular schwannoma: tumor
previous model [16]. Additionally it has a gantry growth and consequences for treatment. J Neurosurg.
2009;110(4):662–9.
with an X-ray tube and image detector, thus 13. Wanibuchi M, Fukushima T, McElveen JT, Friedman
CBCT imaging and intrafraction motion man- AH. Hearing preservation in surgery for large vestibu-
agement are possible. lar schwannomas. J Neurosurg. 2009;111(4):845–54.
8 Gamma Knife 61

14. Sheehan JP, Niranjan A, Sheehan JM, Jane JA, Laws patients with prolactin-secreting pituitary adenomas.
ER, Kondziolka D, et al. Stereotactic radiosurgery World Neurosurg. 2010;74(1):147–52.
for pituitary adenomas: an intermediate review of its 16. Zeverino M, Jaccard M, Patin D, Ryckx N,
safety, efficacy, and role in the neurosurgical treatment Marguet M, Tuleasca C, et al. Commissioning of
armamentarium. J Neurosurg. 2005;102(4):678–91. the Leksell Gamma Knife® Icon™. Med Phys.
15. Tanaka S, Link MJ, Brown PD, Stafford SL, Young 2017;44(2):355–63.
WF, Pollock BE. Gamma knife radiosurgery for
 Linear Accelerator
9
Supriya Mallick and Rony Benson

9.1 What Is a Linear Accelerator? • High energy photons and electrons: with elec-
tronic portal imaging device; multileaf
A linear accelerator is a machine for radiotherapy collimator
treatment which uses high radio-frequency (RF) • High energy photons and electrons: with
electromagnetic waves to accelerate electrons to intensity modulation
high energies in a linear path, using an accelerator
waveguide. The resonating cavity frequency of the
medical LINACS is about 3 billion Hertz (cycles/s). 9.3 Components of LINAC
The current medical LINAC has evolved from DC
voltage accelerators and RF accelerators. The major components of a linear accelerator
(Fig. 9.1).

9.2 Generation of LINACS 1. Drive stand

2. Gantry
• Low energy photons: 4–8 MV 3. Modulator cabinet
• Medium energy photons (10–15 MV) and 4. Treatment table
electrons 5. Control console
• High energy photons (18–25 MV) and
electrons

S. Mallick (*) · R. Benson

Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 63

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_9
64 S. Mallick and R. Benson

E
Drive
Stand

Treatment Coutch

Gantry
Megnetron

Fig. 9.1 Major components of LINAC

9.4 Drive Stand • Lesser average power and gain

• Usually uses 2 MW peak power
Drive stand is the large rectangular cabinet that is • Cheaper, preferred for lower electron ener-
firmly secured to the floor of the room. The gan- gies, 4–6 MeV LINACS
try rotates on horizontal axis in the drive stand. • For higher energies the Klystron is a better
Major components located in the drive stand: choice

1. Klystron or magnetron
2. RF waveguide 9.4.3 Water Cooling System
3. Circulator (connects Klystron to RF
waveguide) • Located in the drive stand
4. Cooling water system • Provides thermal stability to the system
• Helps in maintaining a constant temperature
Microwaves are used to accelerate electrons to so that the components in the drive stand and
the desired kinetic energy. Magnetron acts as a gantry function properly
source of high power microwaves required for
electron acceleration, while a klystron is a micro-
wave amplifier. 9.5 Gantry

• Gantry direct the X-ray (photons) or electron

9.4.1 Klystron beams to the patient
• It rotates 360° around the isocenter
• It is a specialized linear-beam vacuum tube
• Klystron is not a source microwaves but it is There are three main components of the gan-
an amplifier of microwaves try (Fig. 9.2):
• Used in >6 MeV
• Costlier than magnetrons 1. Electron gun
2. Accelerator guide
3. Treatment head
9.4.2 Magnetron

• Provides microwaves—to accelerate the Electron Gun Electrons are produced by elec-
electrons tron guns (Fig. 9.3) by thermionic emission. It
9 Linear Accelerator 65

Schematic representation of a Linear Acclelerator

Accelerator Tube Bending Magnet

Modulated Power Electron Gun

Supply

Magnetron
Via Target and FFF
or
Klystron

Elecron Photon
Treatment Treatment

Fig. 9.2 Schematic representation of a gantry of linear accelerator

• Microwave is produced by klystron or magne-

Pictorial Representation of an Electron Gun
tron and transported to the accelerator structure
Perforated Anode

9.5.2 Treatment Head

Eletrons to
wave guide • Contains beam directing, modifying, and
monitoring devices
• For photon therapy, they consist of the bend-
ing magnet, target, primary collimator, beam
flattening filter, ion chambers, secondary col-
limators, and one or more slots for trays,
wedges, blocks, and compensators

Heated Cathode Bending Magnet Changes the direction of the

Fig. 9.3 Pictorial representation of an electron gun
electron beam, downwards toward the patient

consists of a heated filament cathode and a perfo-

rated grounded anode. • Bends the electron beam towards the target for
X-ray production or toward the scattering foil
for electron treatments
• Produces different beam paths for different
9.5.1 Accelerator Guide energies
• Needed for energies greater than 6 MeV
• It is called the accelerator waveguide. It is • There are two common bending magnet con-
mounted horizontally in the gantry for high figurations, 90° bending and 270° bending
energy single or dual energy machines with (achromatic bending)
klystrons and vertically for low energy
machines with magnetrons
• Waveguides are evacuated or gas filled struc- X-Ray Target The collision of the electrons
tures and are used in the transmission of with the high density transmission target creates
microwaves the X-rays (photons), forming a forward peaking
• Its structure includes series of discs placed at shaped X-ray beam in the direction of the
equal distances with circular holes in the center patient’s tumor.
66 S. Mallick and R. Benson

• The target for X-ray production is positioned 9.5.4 Monitor Ionization Chambers
at the focus of the bending magnet so that
X-rays can be produced efficiently • Ionization chambers monitor dose, dose rate,
• Majority of electron energy [94%] goes into and symmetry of the field
heat • The radiation that leaves the X-ray target or
• Each photon energy has its own unique tar- the electron scattering foils passes through the
get—flattening filter combination dual monitor ionization chambers
• This ionization current is proportional to the
Beam Flattening Filter It is a conical shaped X-ray of electron beam intensity
metal absorber that absorbs more forward peak-
ing photons than the ones in the periphery. It
shapes X-rays in their cross-sectional shape 9.5.5 Multileaf Collimators (MLCs)

• It is required to create a flattened beam with • They are heavy metal field-shaping devices
uniformity and symmetry with independent moving mechanisms used
• Material made to make beam flattening filter— to create a custom like block to spare normal
tungsten, steel, lead, uranium, and aluminum tissue and direct the radiation dose to the
• Dual energy photon LINACS—requires two tumor
flattening filters for the low and the higher • The MLCs became a key element in the
photon energies treatment delivery of X-ray beams with
IMRT (Intensity Modulated Radiation
Therapy)
9.5.3 Scattering Foils • Micro-MLCs—projects 1.5–6 mm leaf widths
at isocenter
• The electron beam needs to be broadened and
made uniform for clinical use
• There is a different scattering foil for each 9.6 Modulator Cabinet
electron beam energy produced
• Made out of aluminum or copper The modulator cabinet is located inside the treat-
ment room and is one of the noisiest part of the
Collimators There are primary collimators as LINAC.
well as secondary collimators (jaw): Contains three subcomponents:

• The primary collimator defines a maximum 1. Fan control

field size. The primary collimator provides a 2. Primary power distribution system
circular field. The secondary collimator 3. Auxiliary power distribution system
­further shapes the field [usually into a square
field [usually 40 × 40 cm]]
• The radiation beams are collimated by adjust- 9.6.1 Newer and LINAC
ing the upper and lower collimator jaws Modifications
• Jaws—made of high Z number, like tungsten
or lead 1. MRI LINAC (Table 9.1)
• The jaws can define a field of up to 40 cm by • LINAC is placed with MRI magnets to
40 cm for X-ray beams improve delineation of target during treat-
• Transmission via jaws—<2% of the open ment to reduce interfraction error and
beam allow dose escalation
9 Linear Accelerator 67

Table 9.1 Types of MRI Linear Accelerators

Equipment Elekta unity ViewRay MRIdian
Photon energy 6 MV 6 MV
MRI 1.5 Tesla 0.35 Tesla

• Important for GI tumors to plan adaptive

radiotherapy
• Accurate target delineation (typically GTV
or tumor bed) [1]
• High risk volume can be better defined by
functional imaging
• Figure 9.4 shows image of ViewRay
Fig. 9.4 Image of ViewRay MRIdian
MRIdian
2. LINAC with FFF beam
• Advantage—FFF X-rays is to provide 1. 1st generation
much higher dose rates for IMRT • 12 interchangeable circular collimators
treatments • SSD of 80 cm
• Dose rates provided are 1400–2400 MU/ • Collimators provide a beam diameter from
min 5 to 60 mm
• Commercially available for treatment 2. Second generation
–– Varian True BEAM—1400 MU/min for • 800 mu/min Linear accelerator
6 MV X-rays and 2400 MU/minutes for • Monte Carlo algorithm for dose
10 MV calculation
–– Elekta—Versa HD • Iris variable aperture collimator
• Especially helpful for SBRT or SRS • RoboCouch
treatments
• Significantly reduces treatment time Disadvantages are as follows:
• Maximum advantage is when treating
small field sizes • No posterior (below couch) possible
3. CyberKnife • Prolonged treatment planning time
• Uses X band LINAC in a robotic arm— • Requires significant quality assurance prior to
uses higher microwave frequency to reduce treatment
the weight of LINAC • Electrons not available for treatment unlike
• Pencil beams of radiation for treatment other LINACS
• Uses orthogonal kV X-ray for image
guidance
• Major advantage of the CyberKnife is its
coupling to the imaging systems which References
continuously monitor organ movement and
feed this back to the robot [2] 1. Liney GP, Whelan B, Oborn B, Barton M, Keall
P. MRI-linear accelerator radiotherapy systems. Clin
• Typically, three radiation beams are deliv- Oncol (R Coll Radiol). 2018;30(11):686–91.
ered and then delivery pauses and a pair of 2. Desai A, Rai H, Haas J, Witten M, Blacksburg
images is acquired—based on these S, Schneider JG. A retrospective review of
images, a corrected position is transmitted CyberKnife stereotactic body radiotherapy
for adrenal tumors (primary and metastatic):
to the robot, which adapts beam pointing to Winthrop University hospital experience. Front
compensate for any patient movement Oncol. 2015;5:185.
• Generations of CyberKnife
 Helical Tomotherapy
10
Supriya Mallick and Rony Benson

Tomotherapy involves delivery of radiotherapy ment of the helical tomotherapy where the
using a fan beam where the target is treated slice machine moves in a helical manner, thereby
by slice. It can be of serial or helical type of avoiding junctions.
tomotherapy.
Serial tomotherapy was the first form of tomo-
therapy clinical use where a normal linear accel- 10.1 Helical Tomotherapy
erator was modified to deliver tomotherapy. The
multivane intensity modulating collimator In this type of tomotherapy the linac head and
(MIMiC) was retrofit into an accelerator and the gantry rotate like a helical diagnostic CT scanner
radiation beam was collimated to a narrow fan while the patient moves into the machine. The
beam defining a trans-axial slice. The MIMiC main advantage of this type of tomotherapy is the
consists of 2 × 20 finger attenuators that can be problem of junctions is minimized because of the
driven into and out of the field. continuous helical motion of the beam (Fig. 10.1).
The serial tomotherapy was one of the earliest Another advantage of helical tomotherapy is the
forms of intensity modulated radiotherapy even megavoltage imaging available with helical
before MLC based intensity modulated tomotherapy [1].
radiotherapy. Another advantage is reduced room shielding
Components of serial tomotherapy are as requirements due to presence of primary beam
follows: stopper I the gantry head. Figure 10.2 shows
structure of a tomotherapy machine.
• Treatment planning system was peacock
• Patient-fixation device—talon
• Ultrasound based target localization—bat

One of the disadvantages of the serial tomo-

therapy was the uncertainty with junctions
between fields as the couch is moved for treat-
ment of a large volume. This led to the develop-

S. Mallick (*) · R. Benson Fig. 10.1 Continuous helical motion of the beam in
Department of Radiation Oncology, National Cancer tomotherapy
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 69

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_10
70 S. Mallick and R. Benson

Tomotherapy Machine

MLC

X ray
Detector

Beam
Stopper

Fig. 10.2 Tomotherapy machine

Table 10.1 Comparison of tomotherapy vs. linear

10.2  ain Properties of Helical
M accelerator
Tomotherapy [2] Conventional linear
Tomotherapy accelerator
• Energy 6 MV X-ray for treatment Single photon energy Dual or triple energy
• Has beam stopper that shields the beam after pass- photons
ing through the patient, hence less room shielding Electrons not available Electron treatment
for treatment possible
is required—precludes need for a primary barrier Imaging is MV Imaging with KV
• The ring gantry also contains a detector system CBCT—better quality
that is mounted opposite to the accelerator and Couch, collimator Couch, collimator rotation
is used to collect data for MVCT acquisition rotation not possible possible
• MVCT imaging performed by 3.5 MeV beam Non coplanar treatments Non coplanar treatments
not possible possible
• Primary collimation produces 0–5 cm slice
width
• Binary MLC—64 leaves
• The leaves are made from 95% tungsten and
are 10 cm thick 10.3 Clinical Uses
• Interleaf transmission—0.5%
• 85 cm gantry aperture 1. Craniospinal irradiation—No junctions and
• No flattening filter (high dose rate)—output better dose distribution
rate 10 Gy/min 2. Total marrow or total lymphatic irradiation—
• Maximum field width 40 cm due to the length of the field unique advantage
• Maximum field length 160 cm of single field technique
• 1–6 rotations per minute 3. Breast cancer—improved homogeneity of
• There is less scatter contamination breast dose and lesser dose to lung when com-
• During treatment full rotation is divided into pared to 3D conformal radiotherapy
51 projections 4. Head and neck radiotherapy—better con-
• Table 10.1 compares tomotherapy to linear formal treatment and allows for adaptive
accelerator RT [3]
10 Helical Tomotherapy 71

10.4 Disadvantages tomotherapy. But in treatments like

craniospinal irradiation, tomotherapy may
­
1. Increase in the integral dose to normal tissues score better.
2. Higher penumbra in the craniocaudal
direction
3. Unavailability of non-coplanar beam References
arrangements
4. Extra dose (up to 0.6–2 cGy) due to MV-CT 1. Piotrowski T, Skórska M, Jodda A, Ryczkowski A,
Kaźmierska J, Adamska K, et al. Tomotherapy: a dif-
5. Electron treatment not possible ferent way of dose delivery in radiotherapy. Contemp
6. Treatment time usually higher than VMAT Oncol (Pozn). 2012;16(1):16–25.
2. Rong Y, Welsh JS. Dosimetric and clinical review
The widespread availability of volumetric of helical tomotherapy. Expert Rev Anticancer Ther.
2011;11(2):309–20.
modulated arc therapy (VMAT) which can be 3. Van Gestel D, Verellen D, Van De Voorde L, de Ost
done in a conventional linear accelerator can B, De Kerf G, Vanderveken O, et al. The potential of
­produce similar dose distribution to tomother- helical tomotherapy in the treatment of head and neck
apy, which has reduced the enthusiasm on cancer. Oncologist. 2013;18(6):697–706.
 Electrons
11
V. R. Anjali

• Electron is a subatomic particle with negative • Through these interactions electron continu-
charge of 1.602 × 10−19. ously loses its kinetic energy, which is
• Discovered by J.J Thompson in 1897. known as continuous slowing down
• Rest energy is 0.511 MeV. approximation.
• Mass is 1/1836 that of proton. • Kinetic energy loss is described by mass stop-
• Stable with mean lifetime of 6.6 × 1028 years. ping power (S/r) and scattering described by
• Radiation dosimetry: electron beam with scattering power (T/ρ).
energies between 1 and 50 MeV—ICRU
21(1972), ICRU 35(1984). Depth dose curve (Fig. 11.2):
• Prescribing, recording, and reporting electron
beam therapy—ICRU 71 in June 2004 • Most probable energy (Ep): Most probable
(Fig. 11.1). energy is the kinetic energy (K.E.) possessed
by most of the incident electrons at phantom
surface.
11.1 Sources • Mean energy (E0): It is the mean energy of
incident electron at the surface of patient.
• Van de Graff generators (1930s). Mean energy is slightly less than Ep.
• Betatron (1940s) • Range: Range is the depth at which the elec-
• Microton tron loses all its kinetic energy in the absorb-
• Linear accelerator (1960s) provides electron ing medium.
energies ranging from 4 to 25 MeV. • The therapeutic range is the depth of an
isodose curve which covers the treatment
volume. Usually depth of 90% isodose
11.2 Interaction with Matter curve of electron beam is taken as the thera-
peutic range, rarely 80% isodose curve is
Electrons while traveling through a medium selected.
interact with atoms (nuclei and electrons) of the • Practical range (Rp): Point of intersection
absorbing medium by Coulomb’s force of inter- of the extrapolated line of bremsstrahlung
action (Tables 11.1 and 11.2). tail and the tangential line through the dose
falloff.
• Maximum range (Rmax): Depth at which
V. R. Anjali (*)
extrapolation of the tail of the central axis
Department of Radiation Oncology, All India Institute
of Medical Sciences, New Delhi, India depth dose curve meets the bremsstrahlung

© Springer Nature Singapore Pte Ltd. 2020 73

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_11
74 V. R. Anjali

Electron beam

Target is removed from beam path

Primary collimator

Flattening filter is replaced by scattering

Scatter foil foil. Scatter α (Z/E)2. Scattering foilis
made of high Z material for spread out
Ion chamber of electrons and made thin to reduce
bremsstrahlung Xray production.
Secondary collimator

Accessory mount

Electron applicator

Lead cut out

Patient surface

Fig. 11.1 A schematic representation of treatment head for electron beam

Table 11.1 Elastic collision of electrons

Elastic collision of With nucleus Nuclear scattering • Causes change in direction of incident
electrons (no loss of With atomic electrons Electron–electron electron (deflection and redistribution)
kinetic energy) of absorbing medium scattering • Scattering α (Z2/K.E2)
• That is why high Z materials are used
for making scattering foils

background. It is the maximum penetration between the phantom surface and the depth of
depth of electrons in absorbing medium. maximum dose.
• R q: Depth at which maximum dose level
intersects with the tangents through the steep- Depth dose distribution formulae for electrons:
est curve of the electron depth dose curve.
• R 90, R 80, R 50: Depth at which the PDDs • Depth of 90% isodose curve, R90 = E/3.2 cm.
beyond the depth of maximum attains values • Depth of 80% isodose curve, R80 = E/2.8 cm.
of 90%, 80%, and 50% isodose, respectively. • Depth of 50% isodose curve, R50 = E/2.33 cm.
• Zmax: Depth of maximum dose. • Practical range Rp = E/2 cm.
• Dose build-up region is the depth region • Mean energy (E0) = 2.33 × R50.
 11 Electrons 75

Table 11.2 Inelastic collision of electrons

Inelastic collision • With atomic electrons Causes ionization and • Ionization and excitation occur in
of electrons (loss of absorbing medium excitation (collision loss) low atomic number material like
of kinetic energy) Two types of collision process water, tissue
• Hard collision—the kinetic energy acquired by • Collision loss depends on electron
the ejected electron is large enough to cause density of the medium
further ionization • α K.E.
• These electrons are known as secondary electrons • Rate of energy loss is greater for low
or delta rays (contribute to dose build up) atomic number material (loss bound
• Soft collision—ejected orbital electrons gain electron, higher electrons per gram)
insufficient energy to ionize its own matter • The rate of energy loss is 2 MeV/cm
• With nuclei Produce bremsstrahlung • X-ray production is more for high Z
X-ray (radiation loss) material and higher energy electron
• Bremsstrahlung production • Radiation loss (bremsstrahlung) is
 6–10 MeV → 0.5–1% proportional to energy and square of
 12–15 MeV → 1–2% atomic number (α Z2, K.E.)
 16–20 MeV → 2–5% • Therefore X-ray production is more
for higher energy electrons and with
higher atomic number

Table 11.3 Surface dose and R90 of different electron

100 energies
90
Percentage Depth Dose (%)

80
Energy (MeV) R90 (cm) Surface dose (%)
70 6 1.7 81
60 8 2.4 83
50 10 3.1 86
40 12 3.7 90
30
15 4.7 92
20
10
18 5.5 96
0 The electron energy is selected so that
Depth Z max Rq R50 Rp R max  R90 is more than the maximum depth of PTV
 Rp is less than the minimum depth of critical
Fig. 11.2 Depth dose curve for electrons structures

• Most probable energy Ep0 = 0.22 + 1.98Rp + • Dose build-up region is broader with higher
0.0025Rp2. energies.
• Energy at depth Z (Ez) = E0 (1 − z/Rp). • PDD increases as energy increases.
• There is rapid dose falloff beyond the maxi-
mum dose (Zmax).
11.3 Features of Electron Beam • Electron beam energy selected should cover
the target volume completely within 90% iso-
• High surface dose, varying from 75% to 95%. dose curve.
• Surface dose increases with increase in elec- • Mean deposition of energy in tissue is 2 MeV/
tron energy. cm.
• There is no skin sparing effect. • Bolus is used to achieve adequate surface dose
• Lower energy scatters more and through larger of 90–100%.
angles, resulting in more rapid build-up • Table 11.3 shows surface dose and R90 of dif-
region, but narrower depth. ferent electron energies.
76 V. R. Anjali

11.4 Isodose Curves • The effect becomes significant when the inci-
dent angle is 45 degrees or more.
• As the electron beam enters a medium scatter- • Bolus can be used to smoothen and reduce the
ing occurs and the beam expands rapidly obliquity.
below the surface.
• In the central region the isodose curves are flat
and closely spaced. 11.7 Bolus
• For low-energy beams all the isodose curve
bulges out. • Flatten out an irregular surface and reduce
• For higher energies only the lower isodose dose inhomogeneity.
curves bulge out, the higher isodose curves • To increase the surface dose (to increase dose
show lateral constriction, which becomes to skin or scar).
worse with decreasing field size • Sparing of distal critical structures.
• 2E (in MeV) mm constriction for 90% isodose • Commonly used materials are paraffin wax,
on each side for the higher energy electrons. polystyrene, acrylic (PMMA), Super Stuff,
Super flab, and Super-flex.

11.5 Effect on Field Size

11.8 Air Gap
• Lateral scatter equilibrium (LSE) exists when
the electron fluence scattered away from an area It is the separation between the end of the appli-
is replaced by electrons scattering into that area. cator cone end and the patient surface. The stan-
• Minimum field radius for LSE (Req) is dard air gap is 5 cm. As the gap increases dose to
Req ≈ 0.88√EP, where Ep is the most proba- the patient will decrease.
ble energy.
• Minimum field size for a square to have LSE
is E/2. 11.9 Field Matching
• When the field is reduced below that required
for lateral scatter equilibrium, (Radius < Req). • Electron–Photon, when an electron field is
–– Dmax and R90 shifts to surface. matched with the photon field, hot spot will
–– Surface dose increases. develop on the side of the photon field due to
–– PDD decreases. scattering of electrons from electron field.
–– Rp remains same. • Electron–Electron, when two electron fields
• Thus, the depth dose distribution for small are matched there will be areas of hot spot due
fields is field size dependent, while for large to bulging isodose curves and areas of cold
fields it is independent of field size. spot depending on the field separation. At the
region of junction there is non-homogenous
dose distribution. Matching is even complex
11.6 Beam Obliquity when the surface is irregular.

• Ideally, electron beam should be incident per-

pendicular to skin surface. 11.10 Field Shaping
• As the beam obliquity increases,
–– Dmax shifts towards surface. • Electron applicators/cones help to hold the
–– Increased surface dose. lead cutouts close to the patient surface and to
–– Reduces therapeutic range. collimate the beam.
–– Penumbra decreases for surface close to • Electron applicators can be closed or open,
source and vice versa. with square or rectangular shape.
11 Electrons 77

• Field shaping is done with lead cutouts of

variable shape. Organ
• For an irregularly shaped field, the radius in at
any direction must be greater than or equal to Risk
Req for the establishment of LSE.
• Internal shielding with lead or tungsten, to
Target Volume
protect the normal structures at risk which are
in close proximity to the target volume.
Internal shielding
• Used in the treatment of lip, buccal mucosa,
earlobe, and eyelid lesions with electrons.
Fig. 11.3 Clinical example for electron planning
• But the electron backscatter from the lead
shield enhances the dose (at interface) to the
tissue in contact with the shield.
• This dose due to electron backscatter can 11.12 Extended SSD
range from 30 to 70%.
• To reduce the effect of electron backscatter, • Reduction in output.
lead shield is coated with suitable material of • Larger penumbra. (Minimized by placing col-
low-atomic number like wax. limation on the skin surface).
• High density material, tungsten is also used for • Minimal change in PDD.
making eye shields. The acrylic/enamel coated
tungsten can shield electron up to 9 MeV.
• The thickness of lead for shielding (mm) is 11.13 Heterogeneity Corrections
given by E(MeV)/2.
• The density of Cerrobend is 20% less com- Dose distribution varies significantly in presence
pared to lead. Therefore, thickness of of tissue inhomogeneity such as lung or bone.
Cerrobend is 20% greater than that of lead. The simplest correction for a tissue inhomogene-
• Another 1 mm is added as safety margin. ity involves the scaling of the inhomogeneity
thickness by its electron density relative to that of
water and the determination of the coefficient of
Thickness of lead = E / 2 ( MeV ) + 1 mm equivalent thickness (CET).
The coefficient of equivalent thickness (CET)
Thickness of Cerrobend = 1.2 × thickness of lead. of a material is given by its electron density rela-
tive to the electron density of water (Table 11.4).

11.11 Case Scenario 1 (Fig. 11.3) • In lung—1 cm thickness of lung is equivalent

to 0.25 cm of tissue. Dose penetration in lung
For example, to treat a target volume of 3 cm depth, is 3–4 times that of unit density tissue. Beam
electron energy of 10 MeV is used. For calculating that penetrates 1 cm in water would penetrate
lead thickness for internal shielding, the energy 4-cm depth in lung having a density of 0.25 g/
reaching at shield tumor interface is calculated cm3.
first. In this case it is 4 MeV (10 − (2 × 3)), 2 MeV • In bone—There will be cold spots beneath
is lost for each centimeter. For protecting the organ bone and hot spots lateral to bone.
at risk, the lead thickness required for internal • In air—Electron penetrates to deeper tissue
shielding is obtained by (4 MeV/2) + 1 mm = 3 mm. and produces hot spot beneath the air cavity.
To reduce the backscatter electrons into the normal There will be areas of hot and cold spots, at
structure the lead is coated with low atomic mate- junction which produces dose inhomogeneity
rial such as wax. up to 20%.
78 V. R. Anjali

Table 11.4 Coefficient of equivalent thickness of vari- • Skin malignancies.

ous tissues • Superficial sarcomas.
Organ Density (g/cm3) CET • IMN irradiation.
Lung 0.25 0.25
Solid bone 1.6 1.6
Spongy bone 1.1 1.1
Air 0.0013
11.15 Special Technique
with Electron Beam

1. Total skin electron therapy.

2. Intraoperative electron beam therapy.
11.14 Common Clinical Uses
3. Total scalp irradiation.
4. Craniospinal irradiation.
• Posterior neck electron boost for nodes in
5. Total limb irradiation.
head and neck malignancies.
6. Electron arc therapy.
• Post-mastectomy chest wall irradiation.
• Boost to the lumpectomy cavity in Ca breast.
 Proton Therapy
12
Supriya Mallick

Researchers from the Lawrence-Berkeley National Protons are positively charged subatomic par-
Laboratory were the first to use proton for clinical ticle with mass 1800 that of electron. Proton ther-
use in the 1950s. The first hospital based proton apy is a type of ionized, particle therapy.
treatments started in 1990 and over the last 3 Figure 12.1 shows type of radiation.
decades there has been a rapid explosion in the
number of centers providing proton treatment.

Radiation

Charged Particle Electro magnetic

Radiation radiation

Ionising Non Ionising

Proton Electron Neutron Heavy Ions Xray & Infra Red
GammaRay Ultraviolet

Fig. 12.1 Types of radiation

S. Mallick (*)
Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 79

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_12
80 S. Mallick

12.1 Interaction of Protons

X-Ray

Protons interact with both electrons nuclei by

Radiation Dose
• Inelastic collisions. Bragg Peak
• Elastic scattering.

12.2 Unit of Dose

• Dose delivered with protons are prescribed as

Cobalt Gray Equivalents (CGE). Dose at Depth

Fig. 12.2 Comparison of X-ray versus proton

12.3  dvantage of Proton Over
A
Photon

Conventional photon energy after incidence in Spread Out Bragg Peak

the skin surface starts interaction and after a
small build-up region deposits its maximum
Radiation Dose

energy (D max). Thereafter energy deposition Tumor

decreases exponentially with increasing depth in
tissue. In that way photon energy has a skin spar-
ing effect but it has a significant exit dose, and a
high integral dose. Protons of different Energies

Dose at Depth
12.3.1 Proton Dose Distribution
Fig. 12.3 Spread-out Bragg peak
• Depends on linear energy transfer (LET).
• Linear energy transfer is energy deposited per
unit path length. 12.3.1.1 Spreading of Braggs Peak
• Rate of energy loss of proton is proportional to There are two methods for spreading the Bragg’s
the square of the particle charge and inversely peak, namely active modulation and passive
proportional to the square of its velocity. modulation
• Energy loss maximum particle—when veloc-
ity approaches zero (near the end of its • Active modulation—In active modulation the
range)—Bragg peak (Fig. 12.2). beam deflected by 2 magnetic dipoles to vary
• Rapid distal dose fall-off after Bragg peak the energy of the beam. Although the treat-
occurs. ment planning is more complex it allows for
• Bragg peak of a mono-energetic proton beam better tailored dose distribution.
is too narrow—Difficult to use clinically. • Passive modulation—In passive modulation
• Superimposition of Bragg peaks of different fixed energy is attenuated by range shifters
energies—wider depth coverage = spread-out of variable thickness (Collimators & com-
Bragg peak (SOBP) [1] (Fig. 12.3). pensators). Treatment planning is simpler
• Lateral penumbra of proton beam at higher than active modulation but the treatment
depth is slightly more than that of photon plan is sensitive to movements of the
beam (few mm). target.
12 Proton Therapy 81

Relative biological effectiveness (RBE): Dose alternating voltage is also applied between
of reference radiation is divided by dose of pro- the Dees as a result of which each time the
ton to achieve similar biological effect. A RBE particles cross the gap from one Dee elec-
value of 1.1 is applied to all proton beam treat- trode to the other particles get acceler-
ments irrespective of other factors. The RBE may ated. Due to this increasing speed the
be higher at the Bragg peak due to higher LET at particles move in circle with increasing
the end of range of the proton with some research- radius in each rotation outward from the
ers quoting a RBE as high as 1.3 [2]. center of the Dees. Upon reaching the
There is a steady increase of LET throughout periphery a small voltage on a metal plate
the SOBP which is significant at the end of the deflects the beam and directs it to hit a tar-
SOBP. This results in an extension of the bio-­ get located at the exit point.
effective range of the beam of a few mm and mer- Advantage of cyclotron over Van de
its consideration in treatment planning. This is Graaff generator:
more important for single field plans or close to a (i) In Van de Graaff generator particles
critical structure. are accelerated by voltage and the
particles’ energy is equal to the accel-
erating voltage.
12.3.2 Parts of Proton Therapy (ii) In cyclotron particles encounter the
System accelerating voltage and leads to very
high output energy.
1. Particle accelerator. (b) Synchrocyclotron
(a) Cyclotron In synchrocyclotron frequency of the
(i) Isochronous cyclotron driving radio frequency electric field is
(ii) Synchrocyclotron varied to compensate for relativistic
(b) Synchrotron effects as the particles’ velocity begins to
2. Beam line approach the speed of light.
3. Gantry (c) Isochronous cyclotron
4. Delivery Systems In the isochronous cyclotron, magnetic
(a) Passive scanning field increases with radius, rather than with
(b) Active scanning time. It requires azimuthal variations in the
(c) IMPT field strength to produce a strong focusing
effect and to keep it in the spiral trajectory.
Protons are produced from hydrogen gas by (d) Synchrotrons
electrolysis of deionized water or from commer- In synchrotrons both the magnitude of the
cially available hydrogen gas. magnetic field and the RF frequency are
varied to maintain a synchronous particle
1. Particle accelerator at a constant orbit radius. The beam aper-
(a) Cyclotron—A cyclotron consists of two ture is small and the magnetic field does
D shaped hollow metal electrodes inside a not cover the entire area of the particle
vacuum chamber known as Dees orbit reducing the cost of the machine.
(Fig. 12.4) which leads to a cylindrical Various particle accelerators are summa-
space within them where the particles rized in Table 12.1.
move. When static magnetic field B is 2. Beamline
applied perpendicular to the electrode (a) The beam exiting from the accelerator has
plane and particles are injected in the cen- a clinically effective range of 70-250 MeV.
ter of the cylindrical space between the (b) The beam is directed by a di-pole magnet
Dees, the particles path bends in a circle and shaped with the help of a quadrupole
due to Lorentz force. A radio frequency magnet.
82 S. Mallick

Section of dees

le
Ordinary path of par tic
Bombardment
chamber
Negative
charge
Thin aluminum “Target” to be Deflection Magnetic Path of
foil window (if bombarded plate (attracts field ion orbit
beam is to pass placed here beam)
into air, with
bluish glow)

Magnet
coil

Helical path Air-tight

of ion starting chamber
at “A”

Window

Target Oscillator
placed
here

Bombardment
chamber

Gas inlet

Magnet coil Two metal halves (dees)

insulated from each other

High voltage oscillator

Window Cyclotron

Path
of ion Deflector

Top view of dees

Fig. 12.4 Schematic representation of a cyclotron

12 Proton Therapy 83

Table 12.1 Accelerator technology comparisons

Type Synchrotron (rapid cycle) Synchrotron (slow cycle) Cyclotron
Energy level selection Continuous Continuous Fixed
Size (diameter) (m) 10 6 4
Average power (beam on) (kW) 200 370 300
Emittance (RMS unnorm.) (μm) 0.2 1–3 10
Repetition rate (Hz) 60 0.5 Continuous
Duty factor (beam-on time) Pulses 20% Continuous

Beamline Cyclotron

Gantry Treatment room Console Area

Fig. 12.5 Parts of a proton treatment system

(c) As proton beam with variable energy may snout, which allows attachment of compensa-
be required to form the SOBP, the beam tor and aperture as required.
passes through a wedge shaped graphite 5. Delivery Systems
filter known as beam degrader. (a) Passive scattering.
3. The proton beam produces significant neutron In case of small fields a single lead scat-
production near the degrader. tering foil is applied to broaden the beam.
4. Gantry: The gantry is a large structure to But single scattering is not adequate for
enable protons with therapeutic energies bent. larger field sizes and may require
In addition it accommodates different beam double-scattering.
monitoring and beam shaping devices (b) Scanning: Scanning is done in x–y axis
(Fig. 12.5). In the treatment nozzles ionization perpendicular to the beam.
chambers may consist of parallel electrode (i) Discrete spot scanning: In this beam
planes divided into horizontal and vertical is delivered to a static position and
strips for quantification of the lateral unifor- once delivered it is moved to the next
mity of the radiation field. The nozzle has spot.
84 S. Mallick

3D CRT Proton Therapy IMRT Proton Therapy

Fig. 12.6 Comparison of IMRT vs proton treatment for craniospinal irradiation and prostate

(ii) Raster scanning: It is similar to spot Figure 12.6 shows IMRT vs Proton treat-
scanning but the beam is not ment for Craniospinal irradiation and Prostate
switched off during transition from cancer.
point to point.
(iii) Wobble scanning. 12.3.2.3 Advantages
(iv) Dynamic scanning: beam is scanned 1. Exit dose less—reduces toxicity
continuously across the target 2. In pediatric tumor—reduces chances of sec-
volume. ond malignancy
3. Skull base/ophthalmic tumor in proximity to
12.3.2.1 Planning critical areas—treatment with required dose
• Broad based: With the introduction of pencil 4. In prostate and other malignancy—dose esca-
beam models broad beam models are being lation is possible, this may result in better
replaced gradually. outcome
• IMPT: IMPT has the following advantages:
–– Improved dose conformality and steeper 12.3.2.4 Disadvantages
dose gradients, 1. For large depths the penumbra for proton
–– Further reduction of integral dose, beams is wider than photons
–– Less sensitivity to range uncertainties and
other sources of uncertainty.

12.3.2.2 Indications References

• Standard Indications [3]
–– Pediatric tumor 1. Jette D, Chen W. Creating a spread-out Bragg peak in
proton beams. Phys Med Biol. 2011;56(11):N131–8.
–– Skull base tumor 2. Paganetti H, Olko P, Kobus H, Becker R, Schmitz T,
–– Ophthalmic tumor Waligorski MP, Filges D, et al. Calculation of relative
–– Carcinoma prostate biological effectiveness for proton beams using bio-
–– Brain tumor logical weighting functions. Int J Radiat Oncol Biol
Phys. 1997;37(3):719–29.
–– Craniospinal irradiation 3. Mishra MV, Aggarwal S, Bentzen SM, Knight N,
• Evolving evidence Mehta MP, Regine WF. Establishing evidence-based
–– Lung cancer indications for proton therapy: an overview of cur-
–– Breast cancer rent clinical trials. Int J Radiat Oncol Biol Phys.
2017;97(2):228–35.
–– GI cancer
 Radiation Facility Development
13
Ritesh Kumar and Divya Khosla

International Agency for Research on Cancer has best located where it adjoins the earth on several
estimated that there were 18.1 million new cancer sides and has no departments below, thus the
cases and 9.6 million cancer deaths in 2018 [1]. basement or ground floor would be the most suit-
There is a gradual increase in cancer burden world- able location. It should have mandatory thick
wide [2]. Radiotherapy is an integral component of walls and ceilings for radiation protection and
multimodal cancer treatment and approximately required access for the placement or removal of
50–60% of people who develop cancer will require equipment. It should be near to the outpatient
radiotherapy at some point [3]. Therefore, for an department and transport facilities as most of the
effective management strategy for cancer, radiation patients are outpatients.
facility is essential and should be within reach of
patients [4]. Establishment of radiation facility is
expensive, and different newer machines are required 13.2 Radiotherapy Equipment
in a tertiary care center to deliver the state-of-the-art
treatment to the patients. A radiation oncologist The radiotherapy equipment required in a tertiary
needs to be in the forefront for creation of an effec- care institute comprises of teletherapy units and
tive radiation facility. This chapter will concentrate brachytherapy units. Teletherapy machines
on the basics on creation of a radiation facility. deliver radiation from a distance, i.e., radiation
sources are at a distance of 80–100 cm from the
patient. Brachytherapy machines deliver radia-
tion from a short distance, i.e., radiation sources
13.1 Location are placed inside or near the tumor [5].

The location of the department is according to the

radiation protection guidelines for the design of 13.3 Teletherapy Units
structural shielding for radiation installations
(NCRP Reports 49 and 51). Radiation facility is 1. Telecobalt
Telecobalt was earlier one of the most
R. Kumar (*) widely used machines for the teletherapy
Department of Radiation Oncology, All India Institute treatment. It uses Cobalt-60 radioisotope
of Medical Sciences, New Delhi, India which emits high energy gamma rays that are
D. Khosla used for the treatment. It is a simple and rela-
Department of Radiation Oncology, Post Graduate tively cheap machine. The radioactive source
Institute of Medical Education and Research,
Chandigarh, India has to be replaced every 5–10 years.

© Springer Nature Singapore Pte Ltd. 2020 85

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_13
86 R. Kumar and D. Khosla

2. Linear Accelerator tumor as per the required dose and treatment

Linear accelerator (LA) electrically gener- planning. Thus, a very high dose to the tumor
ates high energy X-rays for the treatment. It is is delivered in a short time with sparing of
now the most widely used machine worldwide normal tissues.
for the teletherapy treatment. With improve- (a) LDR (low dose rate) equipment
ment in technology, various modifications Delivers radiation at low dose rate (0.2 to
have been incorporated in a LA to deliver 2 Gy per hour)
high-tech radiation modality in form of Radium-225 is used as radioisotope
(a) 3DCRT (Three Dimensional Conformal Requires inpatient admission. Cannot be
Radiation Therapy) done on outpatient basis.
(b) IMRT (Intensity Modulated Radiation (b) HDR (high dose rate) equipment
Therapy) Delivers radiation at high dose rate
(c) VMAT (Volumetric Modulated Arc (>12 Gy per hour)
Therapy) Iridium-197 is used as radioisotope
(d) IGRT (Image Guided Radiation Therapy) Can be done on outpatient basis
(e) SBRT (Stereotactic Body Radiotherapy) 3. Operation theater
3. Gamma Knife Brachytherapy facilities require anesthesia
This is a high precision radiotherapy machine in most of the cases. Thus, operation theater
for treating small intracranial tumors. It delivers facilities are required. A dedicated brachy-
very high dose of radiation to a small area in therapy suit operation theater is preferred.
brain with a high degree of accuracy while
effective sparing of critical normal structures. It
uses Co-60 as radiation source. This technique 13.5 Personnel Requirements
is known as stereotactic radiosurgery (SRS).
4. Simulator The organizational team consists of radiation
A simulator is a machine which simulates oncologists, medical physicists, radiation tech-
the teletherapy machine and is used for radia- nologists, nurses, counsellor, and a dietitian [7].
tion treatment planning. Various types of simu-
lators are required as per the treatment plan, i.e., 1. Radiation oncologist
(a) Conventional simulator—2-dimensional The head of the radiotherapy department is
treatment planning a radiation oncologist. Radiation oncologist is
(b) CT-simulator—3-dimensional treatment a doctor who is trained in the use of radio-
planning (3DCRT/IMRT) therapy and is responsible for prescribing and
(c) 4D-simulator—Respiratory gating is pos- supervising radiation treatment.
sible (IGRT) 2. Medical physicists
A radiation expert—who helps to plan the
treatment with the oncologist. Together they
13.4 Brachytherapy Units will decide the best way of giving the pre-
scribed amount of radiation. The physicist is
1. Sources also responsible for making sure the radio-
Radioisotopes are required to deliver the therapy equipment is used accurately. He
brachytherapy treatment. The most common monitors the technical issues and radiation
and widely used radioisotope for brachyther- safety issues.
apy is Iridium-192 (Ir-192). Other radioiso- 3. Technologists
topes used are Cesium-137, Iodine-125, Operate the machine and deliver the pre-
Palladium-103, and Gold-198 [6]. scribed radiation dose to the patient. They
2. Equipment are trained in giving radiotherapy and in
The machine stores the radioisotope in safe patient care. They help patients cope with
position and the isotope is moved near the any problems during the treatment, can give
13 Radiation Facility Development 87

information, support, and counselling. They 5. Procurement of Personnel Monitoring

work closely with radiation oncologist and a Devices for monitoring of radiation dose
physicist to plan and execute radiation 6. Measuring and monitoring instruments
treatment. 7. Authorization to procure radiation sources
4. Mould room assistant 8. Road transport approval
A technical staff who prepares accessory 9. Receipt of sources
devices which are used in patient treatment 10. Installation of the unit
and radiation beam modification. 11. Loading of the source/switching on radiation
5. Nurses in case of radiation generating equipment
Nurses look after patient’s general needs 12. Quality assurance/acceptance test
such as dressings and medicines. The nurses 13. Commissioning approval for patient treatment
also give information and advice about the 14. Periodic performance/quality assurance test
treatment, as well as practical support. 15. Annual status report
6. Dietitian
A dietitian advices regarding dietary man-
agement during radiotherapy, problems of eat- 13.7 Radiation Protection
ing and drinking during the radiotherapy
treatment (for example—difficulty in swal- A radiation protection program is defined as the
lowing or a dry mouth). sum of all methods, plans, and procedures used to
7. Speech and language therapists protect the health and environment of personnel
A speech and language therapist helps the from exposure to sources of ionizing radiation.
patients receiving radiation to neck region The principle of ALARA (as low as reasonably
regarding the voice changes and recovery achievable) is followed. The authority of the
after radiotherapy. Radiation Safety Program is delegated to the
8. Social worker Director, Radiation Safety Officer (RSO), and
Social worker gives advice about any non-­ ultimately to the Radiation Safety Committee.
medical problems including practical and Monitoring in radiation protection is essen-
financial help. Social workers can also pro- tially required to assess compliance with estab-
vide or arrange counselling and emotional lished dose limits. Personnel monitoring, area
support for the patient and family. monitoring, and environmental monitoring need
9. Palliative care team to be performed to ensure radiation safety [8].
Gives extra help and support to people with
symptoms or side effects of treatment that are 1. Personnel monitoring
causing problems. Palliative care is specially Personnel monitoring is performed by
important for terminally ill patients. making external and internal dose measure-
ments. Thermoluminescent dosimeters
(TLD), film badges, fast neutron monitors,
13.6 Requirements and direct reading dosimeters are used for
and Guidelines external dose measurement on personnel.
for Procurement of Radiation 2. Area monitoring
Equipment [7] Area monitoring includes measurement of
radiation dose rates, airborne activities, and sur-
1. Clearance of the radiation therapy unit by the face contamination. Monitoring devices like
national regulatory board ionization chamber, proportional counter, Geiger
2. Approval of room layout plan of radiation Muller tube, and scintillation detector are used.
therapy installation 3. Environmental monitoring
3. Appointment of radiation therapy staff Environmental monitoring is used to detect
4. Nomination and approval of radiological any significant increase of radiation dose
safety officer above background.
88 R. Kumar and D. Khosla

13.8 Disposal of Radiation Waste tion oncologists, medical physicists, radiation

technologists, mould room assistants, and other
Improper disposal of radioactive waste presents support staff. Radiation machines have high tech-
potential hazards to the general public. The pro- nological requirements, and radiation safety
gram director and the RSO are responsible for the issues are the most important aspect which can-
proper storage and disposal of radioactive waste. not be overlooked.
Radioactive waste should be stored properly in
closed containers and should be labeled with a
“Caution Radioactive Material” sticker. The stan- References
dard operating procedures for disposal of radio-
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA,
active sources are mentioned below [8].
Jemal A. Global cancer statistics 2018: GLOBOCAN
estimates of incidence and mortality worldwide
1. The licensee/authorized user initiates necessary for 36 cancers in 185 countries. CA Cancer J Clin.
regulatory procedures with the help of RSO. 2018;68(6):394–424.
2. The RSO helps the licensee in filling up the 2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers
C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer
relevant regulatory forms and coordinate with incidence and mortality worldwide: sources, methods
the AERB for obtaining necessary approval and major patterns in GLOBOCAN 2012. Int J Cancer.
for the safe disposal of radioactive sources. 2015;136(5):E359–86.
3. The permission to transport the radioactive 3. International Atomic Energy Association. Millions
of cancer victims in developing countries lack access
waste is also obtained from AERB. to life saving radiotherapy. http://www.iaea.org/
4. The decayed/disused radioactive sources are NewsCenter/PressReleases/2003/prn0311
sent to the original supplier of the source. 4. Stewart BW, Kleihues P. World cancer report. Lyon:
5. Under no conditions, the radioactive waste is International Agency for Research on Cancer press;
2003.
treated as ordinary waste or abandoned/dis- 5. Halperin EC, Perez CA, Brady LW. Perez and Brady’s
posed off in public. principles and practice of radiation oncology. 5th ed.
Philadelphia: Lippincott Williams & Wilkins.
6. Khan FM. Physics of radiation therapy. 4th ed.
Philadelphia: Lippincott Williams & Wilkins.
13.9 Conclusions 7. Setting up a radiotherapy programme: clinical, medical
physics, radiation protection and safety aspects. IAEA,
Radiotherapy facilities form an important part of 2008.
8. Radiation Protection Manual. A publication of Institute
comprehensive cancer care in a tertiary care insti-
of Nuclear Medicine and Allied Science (INMAS),
tute. It requires a team approach including radia- DRDO, 2010.
 Intraoperative Radiotherapy
14
Supriya Mallick and Goura K. Rath

Intraoperative radiotherapy (IORT) enables 2. Mobile intraoperative electron accelerator:

delivery of radiation directly to the operated (a) Mobetron- ELIOT
tumor bed in the operation theater, thereby (b) LIAC
reduces the requirement of extra anesthesia and A summary of mobile intraoperative
completes entire adjuvant treatment or the boost electron accelerator is shown in
phase of the adjuvant radiation. Fig. 14.1.
3. Mobile X-ray based equipment (Fig. 14.2):
(a) Intrabeam (Zeiss)—Intrabeam comes
14.1 Types with XS4 miniaturized linear accelerator
with an inbuilt internal radiation monitor
1. Intraoperative HDR brachytherapy: for real time dose monitoring
(a) Hamburg applicator (b) Papillon (Ariane)
(b) Freiberg applicator (c) Xoft (iCAD)

S. Mallick (*) · G. K. Rath

Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 89

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_14
90 S. Mallick and G. K. Rath

Equipment Mobetron LIAC-HWL

Self-shielded electron-beam linear Self-shielded electron-beam linear

accelerator (LINAC) accelerator (LINAC) machine
machine, Integrated Shielding
Energy 6 MeV, 9 MeV, 12 MeV 4, 6, 8, 10, 12 MeV:
Dose Rate 10 Gy/Min 10 Gy/Min
Indication
Applicators Range of field sizes from 3 to 10 cm in . 5 cm PMMA applicator,
increments. Bevel angles: 0°, 15°, 30°, 45° Bevel angles: 0°, 15°, 30°, 45°
Precise Soft Docking Alignment Hard Docking Alignment

Stray radiation 0.2 µsV/Gy at 3 m

Image

Fig. 14.1 Mobile intraoperative electron accelerators

Equipment Intrabeam Papillon Xoft

Energy (kV) 50 50 40, 50, 60

Current (mA) 0.04 0.1, 0.5 0.3

Indication Breast, Skin, Brain, GI Breast, Rectum, Skin Breast, Skin, Gynecology

Image

Fig. 14.2 Mobile X-ray based intraoperative brachytherapy machines

14 Intraoperative Radiotherapy 91

14.2 Comparison of Intraop 14.3 Applicators

Electron vs. Intraop HDR
Brachytherapy The common applicators and peculiarities of
applicators are summarized in Fig. 14.3.
Intraop electrons are costlier but less time con-
suming than intraop HDR brachytherapy. Other
differences are described in Table 14.1. 14.4 Clinical Uses
Table 14.1 Comparison of intraop electron vs. intraop Patient selection is very important for successful
HDR brachytherapy
implantation for intraoperative radiotherapy pro-
Intraop HDR tocols. Generally patients selected are those in
Intraop electron brachytherapy
whom surgery alone is unlikely to achieve good
Costlier Cheaper
Treatment time 2–4 min Treatment time 4–30 min local control and close margins are anticipated
Total procedure time less 30 min More time 60–120 min and EBRT alone may not give adequate doses for
Only in accessible locations Any area tumor control.

Applicator Commend Image

Flat Applicator Surgically exposed surfaces

Surface Applicator Tumors on the surface of the body

Needle Applicator

Hams Applicator Silicone rubber

8mm in thickness
Catheters spaced 1cm apart Flexible

Frieberg Applicator Large and curved anatomies

Easy to match treatment area
Reproducible dosimetry

Fig. 14.3 Common applicators used for intraoperative radiotherapy

92 S. Mallick and G. K. Rath

Table 14.2 Important trials on intraoperative radiotherapy

Trial Comparison Dose Inclusion Criteria Result
ELIOT trial, Phase EBRT vs. IOERT 21 Gy Age ≥48 and <75 Local recurrence (LR)
III (n = 1305) Unifocal breast carcinoma rate 4.4%
≤2.5 cm
TARGIT-A Phase III, EBRT vs. IORT 20 Gy Age ≥45-years 5 year LR: 1.3% vs. 3.3%
(n = 3451) Breast cancer T1–T2 ≤ 3.5 cm, 2.5% non-inferiority
N0–1 margin not achieved
TARGIT-B IORT boost with 20 Gy EBC with high risk of local NA
EBRT boost recurrence
TARGIT-E Phase II IORT 20 Gy Age ≥7 years Ongoing
(n = 265) Unifocal breast cancer, cT1c N0
M0, IDC, No LVSI

Another potential advantage of IORT is the References

higher biologic effectiveness of a single dose of
IORT. The main dose limiting structure espe- 1. Veronesi U, Orecchia R, Maisonneuve P, Viale G,
cially in sarcomas of extremity, pelvis, or retro- Rotmensz N, Sangalli C, et al. Intraoperative radio-
peritoneum is peripheral nerve. therapy versus external radiotherapy for early breast
cancer (ELIOT): a randomised controlled equivalence
Indications—stomach, pancreas, retroperito- trial. Lancet Oncol. 2013;14(13):1269–77.
neal and pelvic sarcomas pelvic, breast [1–3]. 2. Vaidya JS, Joseph DJ, Tobias JS, et al. Targeted intraop-
Important trials on intraoperative radiotherapy erative radiotherapy versus whole breast radiotherapy
are summarized in Table 14.2. for breast cancer (TARGIT-A trial): an international,
prospective, randomised, non-­inferiority phase 3 trial.
Lancet. 2010;376(9735):91–102.
3. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted tar-
14.5 IORT Dose geted intraoperative radiotherapy versus whole-breast
radiotherapy for breast cancer: 5-year results for local
control and overall survival from the TARGIT-A ran-
• Boost 10 to 20 Gy, depending on the amount domised trial. Lancet. 2014;383(9917):603–13.
of tumor remaining after maximal resection
• Breast IORT: 20–21 Gy.
 Part II
Practical Brachytherapy
 Evolution of Brachytherapy
15
V. R. Anjali

• Wilhelm Conrad Roentgen is a German physicist

• Discovered X-ray in 1895
• First Nobel Prize for Physics in 1901
• Radioactive element Roentgenium 111 is named after him

• Marie Curie and Pierre Curie

• In 1898, extracted radium from pitchblende ore
• Coined term radioactivity
• Pierre Curie—Nobel Prize for Physics (1903)
• Marie Curie received Nobel Prize for Physics (1903) and Chemistry (1911)
• Discovered radioactive element polonium

V. R. Anjali (*)
Department of Radiation Oncology, All India Institute
of Medical Sciences, New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 95

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_15
96 V. R. Anjali

15.1 Dosimetric Systems 15.1.3 Manchester System

in Intracavitary
Brachytherapy • Described by Todd and Meredith in 1938 at
Holt Radium Institute.
1. Stockholm system • Fractionated dose in two applications.
2. Paris system • Each treatment duration of 72 h (total
3. Manchester system 144 hours) with 4–7 days gap between each
treatment.
• Intrauterine tube
15.1.1 Stockholm System –– Thin intrauterine rubber tubes are used—
two standard lengths of 4 cm and 6 cm and
• Introduced in 1910 by Gosta Forssell et al. in one nonstandard length of 3.5 cm.
Radiumhemmet. • Vaginal ovoids
• Fractionated course of radiation in 2–3 appli- –– The ovoids are fixed and held apart by
cations over 3 weeks. spacer at distance of 1 cm. In narrow vagina
• Each treatment lasting for 20–30 h separated ovoids are held in position by washers.
by 1 week. –– Largest ovoid is placed to obtain maximum
• Flexible intrauterine rubber tubes with lateral throw off.
30–90 mg of radium. • Defined 1 unit as 2.5 mg of radium filtered by
• Vaginal applicators/boxes (silver/gold) con- 1 mm Pt, and all loadings in the intrauterine
tained 60–80 mg of radium. tube and ovoids were made in terms of inte-
• Uterine and vaginal applicators are not fixed gral multiples of this unit.
to each other, held in approximation by gauze • Tables 15.1 and 15.2 describe loading pattern
packing. for intrauterine tubes and ovoids
• No fixed geometry was present.
• Used unequal loading pattern in uterine and 15.1.3.1 Defined
vaginal applicators. • Paracervical triangle—The loose areolar fas-
• Total dose of 6500–7100 mg Ra was pre- cia between the broad ligament is the parame-
scribed, and 4500 mg Ra was from vaginal trial fascia and the firm supporting tissue
applicator, dose rate of 110R/h. surrounding cervix is paracervical fascia.
Paracervical triangle is roughly pyramidal in
shape, with its base resting on the lateral for-
15.1.2 Paris System nix and the apex curving round with the ante-
verted uterus. Dose to this region gives
• Developed in 1919 by Regaud, Lacassagne tolerance dose for normal tissue.
et al. at Institute of Radium, Paris.
• Single application. Table 15.1 Loading pattern for intrauterine tubes, from
• Treatment time of 120 h (5–8 days). fundus to cervix
• Intrauterine tubes with three radioactive IU Tubes Length Units Total radium (mg)
sources with source strength of ratio Long 6 6-4-4 35
1:1:0.5(13.33, 13.33, 6.66 mg). Medium 4 6-4 25
• Vaginal applicators as two cork colpostats Short 2 8 20
connected to each other by metallic spring.
• Not a fixed geometry. Table 15.2 Loading pattern for ovoids
• Total dose of 7200 mg–8000 mg h Ra. Ovoids Diameter (cm) units Total radium
• Contribution from intrauterine and vaginal Large 3 9 2.5 × 9 = 22.5 mg
applicators were equally divided ~ 3600– Medium 2.5 8 2.5 × 8 = 20 mg
4000 mg h Ra from each. Small 2 7 2.5 × 7 = 17.5 mg
15 Evolution of Brachytherapy 97

Table 15.3 Summary of Stockholm, Paris, and Manchester system for brachytherapy
Dosimetric
system Stockholm system Paris system Manchester system
Year 1910 1912 1930
Number of Fractionated Single application Fractionated
fractions
Treatment 2–3 fraction, each treatment period 20–30 h, Treatment over 120 h in In 2 fractions,
duration separated by 1 week 5–8 days 1 week apart
Treatment over 1 month Each treatment over
72 h
Total treatment of
144 h
Intra uterine Rubber with 30–90 mg of radium Rubber tubes Rubber tubes
tubes
Intravaginal Vaginal boxes with 60–80 mg of radium. Cork/vaginal Colpostats Ovoids
Loading pattern Unequal Equal Unequal
Geometry Not fixed Not fixed Not fixed
Total dose 6500–7100 mg-h 7000–8000 mg-h 7500R at point A
4500 by vaginal boxes Over 5 days
Dose rate 110R/h 45R/h 53R/h

• Point A is 2 cm lateral to the central canal of the 15.3 Modified Fletcher

uterus and 2 cm from the mucous membrane of Techniques
the lateral fornix in the axis of the uterus. It
reflects the dose to the paracervical triangle. 15.3.1 Fletcher Suit Modification
• Point B is 5 cm from the mid-line and on the
same level as Point A. It gives the dose • In the 1960s Suit et al. modified the Fletcher
received by obturator nodes. applicator for using afterloading technique
• Aim is to deliver an exposure of 8000 R at with standard radium tubes to reduce the radi-
55.5 R/h to Point A and 3000R to Point B. ation exposure.
• Table 15.3 summarizes Stockholm, Paris, and • The afterloading ovoids are of the same diam-
Manchester system for brachytherapy eter as the Fletcher ovoids, but are 1 mm
longer.

15.2 The Fletcher Technique

15.3.2 F
 letcher Suit Delclos (FSD)
• Developed by Fletcher et al. at MD Anderson Modification
Hospital in 1940.
• Combined dosimetry from Paris and • In the 1970s Delclos developed mini ovoids
Manchester system. with diameter of 1.6 cm and flat medial sur-
• Tandem and ovoids were designed for the use face, for using in narrow or distorted
of preloaded radium source. vagina.
• Used high density metal (tungsten alloy) • No shields were used for mini ovoids.
shields to reduce the dose in antero-posterior • Smaller diameter and no shielding resulted in
direction, without compromising dose to the high vaginal surface dose.
paracervical region. • It was compatible with remote afterloading
• The rectal and bladder shields were present in technique.
ovoids.
98 V. R. Anjali

15.3.3 Fletcher Green Modification • Superficial lesion <5 mm in vagina.

• Figure 15.2 shows tandem and cylinder
• Green et al. modified the Fletcher applicator applicator
with afterloading ovoids, less bulky, round han-
dles, and a simpler radium holder mechanism.
15.7 Tandem and Mold Technique
For the Fletcher family of colpostats due to
shielding of ovoids, the radiation dose in the • Creteil method
anterior posterior direction is reduced by –– One intrauterine source and two vaginal
15–25%. But after considering the dose from the sources. Alginate impression/acrylic mould
uterine tandem the net reduction in dose intensity of vagina is taken.
is ~10–15% –– Uses 192Ir wires.
–– The maximum dose prescribed is 60 Gy.
• Institut Gustave Roussy method
15.4 Henschke Applicator –– Intrauterine source of varying length cov-
ers at least lower two third of the uterus.
• In 1960, Henschke developed a flexible appli- –– Two vaginal sources, parallel to each other.
cator system to permit manual afterloading. –– A dose of 60 Gy is prescribed to this refer-
• Radioactive sources of cobalt 60, iridium 192, ence isodose.
cesium 137, or radium were used.

15.8 Dosimetric System

15.5 Tandem and Ring Technique for Interstitial Brachytherapy

• Intrauterine tandem of varying angle and 1. Paterson–parker system/Manchester system

length, and ring of different diameter. 2. Quimby system
• Vaginal ring is perpendicular to the tandem 3. Paris system
and lies in the fornix.
• E.g.: Vienna ring applicator (Fig. 15.1)

15.6 Tandem and Cylinder

Technique

• Narrow vagina.
• To treat varying length of vagina.
• Intrauterine tandem of varying length.
• Vaginal cylinders of varying diameter from 2
to 4 cm are available. Fig. 15.2 Tandem and cylinder applicator

Fig. 15.1 Vienna ring

applicator 33º

11mm
15 Evolution of Brachytherapy 99

15.8.1 Manchester System\Paterson– lel to each other, and if they differ in area, then
Parker System the average area is used to determine the mg-­
hrs and the activity is proportioned to each
• The Manchester system was developed by plane. Figure 15.3 summarizes the types of
Ralston Paterson (radiation oncologist) and implants.
Herbert M Parker (physicist) at Holt Radium –– The rules for the Manchester system are
Institute, Manchester in the 1930s. established for geometrical volumes of
• Non-uniform distribution of activity to yield tissues: either slabs of uniform thickness
uniform distribution of dose. of rectangular area or cylinders and
spheres.
15.8.1.1 D  istribution Rules for Planar –– The given target volume is included in such
Implantation a volume for the implantation.
• Needles to be arranged in parallel to each –– Sources are distributed based on the size of
other in a row. the target area, with more source strength
• Spacing between the needles should not be concentrated in the periphery for compen-
more than1cm. sating for the dose fall-off, thereby improv-
• Deliver a uniform dose of ±10% from the pre- ing dose uniformity.
scribed or stated dose throughout the volume –– Ratio of amount of radium in periphery and
to be treated. center depends on the area of implant
• Active ends are crossed by crossing needles at (Table 15.4).
right angles to the implant and placed not –– Correction factors are used for plane sepa-
more than 1 cm from active ends. rations larger than 1 cm in order to achieve
• If ends are uncrossed effective area of dose dose homogeneity of ±10% than the pre-
uniformity is reduced. The area is reduced by scribed dose (Table 15.5).
10% for each uncrossed end for planar implant. • Mid plane dose for thick target volumes can
• If multiple planes are used, the separate planes be as much as 20–30% lower than the pre-
should be arranged as for single planes, paral- scribed dose.

IMPLANTS

PLANAR
IMPLANTS
VOLUME
IMPLANTS
(Tissue > 2.5 cm)
SINGLE PLANE DOUBLE PLANE
(Tissue < 1 cm thick) (Tissue up to 2.5 cm thick) Cylinder Cube Sphere

Fig. 15.3 Types of implants

Table 15.4 Table showing area, fraction used in periph- Table 15.5 Table showing correction factor for various
ery, and activity at center separation
Area (cm2) Fraction used in periphery Activity at center Separation (cm2) Correction factor
<25 2/3 1/3 1.5 1.25
25–100 ½ ½ 2.0 1.4
>100 1/3 2/3 2.5 1.5
100 V. R. Anjali

15.8.1.2 Volume Implant 15.8.2 Quimby System

• Tumor containing tissue is encompassed in
simple geometric form such as cylinder, • The Quimby system was developed by Edith
sphere, or cube. Quimby et al. at New York Memorial Hospital
• Sources are placed as evenly as possible not in the 1930s.
more than 1.0 to 1.5 cm apart. • Uniform distribution of sources of equal linear
• Volume is considered with 75% activity at sur- activity, resulting in non-uniform dose
face and 125% activity at the core (Table 15.6). distribution.
• Activity divided into eight parts and distrib- • Usually, the dose in the center of the treatment
uted depending on the shape of the volume volume is higher than the dose near the
(Table 15.7). periphery.
• For volume implant, 7.5% is reduced from • Central dose is typically 25–30% higher than
volume for each uncrossed end. the prescribed dose.
• Volume implants have different sets of rules • Distance between sources is 1–1.5 cm.
and tables.
• Table reading is correct, where all dimensions
are equal or the longest side or diameter is less 15.8.3 Paris System
than 1.5 times the shortest.
• When ratio exceeds the limit, correction for • Developed by Pierquin and Dutreix in the
elongation is required (Table 15.8) 1960s in Paris for flexible 192Ir wire.
• The active sources should be linear and paral-
lel to each other.
Table 15.6 Table showing activity at core, ends and • Sources should be equidistant from each other
outer parts spacing between adjacent sources is not less
Outer part/rind/belt 50% activity than 8 mm or more than 15 mm.
Core 25% activity • The linear activity must be uniform and iden-
Ends 12.5% activity on each end. tical for all sources.
• The plane on which the midpoints of the
Table 15.7 Table showing activity divided depending on sources lie, the central plane, should be per-
the shape of the volume pendicular to the axis of each source.
Sphere Cylinder Cube • Used for single and double plane implants and
Belt—6 part Belt—4 part Belt—6 part not for other types of volume implant.
Core—2 part Core—2 part Core—2 part • The active sources should be 20 to 30 percent
Ends—2 part
longer than the target volume at both ends, to
compensate for the uncrossed ends.
Table 15.8 Elongation factor and elongation correction • The basic concepts of Paris system are sum-
Elongation factor Elongation correction (%) marized in Table 15.9.
1.5 3
2.0 6
2.5 10
3 15
15 Evolution of Brachytherapy 101

Table 15.9 The basic concepts of Paris system

Central plane:
• Plane at which the midpoint of sources lies, and it is
at the right angle to the long axis of the sources
• Dose is specified within the target volume, in the BD1 BD2 BD3
Central Plane
central plane

Basal dose rate (BD):

• Basal dose rate is the minimum dose rate between a
pair or group of sources
• It is the arithmetic mean of the minimum dose rates
BD2
between the sources within the implant along the Central Plane
central plane
BD1 BD3

BD = (BD1 + BD2 + BD3) / 3

Central Plane

BD1 BD2

BD = (BD1 + BD2) / 2

Reference dose rate (RD):

RI = 85 % BD
• Defined as 85% of the basal dose rate
• Dose is prescribed to the reference isodose line
BD
• RI = 0.85 × BD

170 100 70 20% BD

120 85 50
 Basics of Brachytherapy
and Common Radio Nucleotides 16
V. R. Anjali

16.1 Basics of Brachytherapy 1 Curie ( Ci ) = 3.7 × 1010 Bq.

An element with same atomic number (num-
Brachytherapy is a method by which radiation
ber of protons are same) but with different mass
treatment is delivered with the help of sealed
numbers (number of neutrons are different) is
radionuclide which is kept close to the target tis-
known as isotope. If the isotopes of an element
sue. The factors which contribute to the thera-
have the property of radioactivity and undergo
peutic effect of treatment include specific
radioactive decay, then it is called radioisotope/
activity, range, photon energy, and half-life of
radionuclide. Radionuclide decays in one or
radionuclide (Table 16.1).
more step, with series of decay products. The
final stable atom produced in the decay chain will
not be radioactive.
16.2 Common Radionuclides
For elements with atomic number greater than
82, the interaction between the attractive force
Radioactivity is the property of substances to
(nuclear binding energy) and the repulsive force
undergo spontaneous disintegration, with emis-
(between protons) becomes large enough to over-
sion of particle (alpha, beta, and neutrons) or
come the attractive force and undergoes radioac-
radiation or both due to instability of the nucleus.
tive decay.
Antonie Henry Becquerel discovered radioactiv-
ity in 1896 and won Nobel Prize for Physics in
1903.
16.2.1 Types of Radioactive Decay
Activity is defined as the number of disinte-
grations per unit time. SI unit of radioactivity is
16.2.1.1 Alpha Decay
Becquerel (Bq). Old unit is Curie, defined as
• Radioactive element disintegrates by emission
activity of 1 gram of radium 226, which is
of alpha particle.
3.7 × 1010 disintegrations per second.
• Atomic number is reduced by two and mass
1Becquerel = 2.7 × 10 − 11Ci. number by 4.
• E.g. 88 RA226 → 86 Rn222 + 2
He4 + 4.87 MeV.
V. R. Anjali (*)
Department of Radiation Oncology, All India Institute Beta decay—Decays by emission of negatron
of Medical Sciences, New Delhi, India or positron from the nucleus.

© Springer Nature Singapore Pte Ltd. 2020 103

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_16
Table 16.1 Brachytherapy treatment types depending on dose rate
104

Dose Rate Sources Radiobiology Advantage Disadvantage

192
High dose rate (HDR) >12 Gy/h Ir, • Better cell kill at higher dose rate • Allows dose optimization by changing • Poor therapeutic ratio
60
Co • Short treatment time doesn’t dwell position and dwell time • Source gets stuck high dose of
allow repair of sublethal damage • Short duration of treatment- less radiation exposure to patient and
• At higher dose rate, detrimental patient discomfort, helps maintain staffs
effect on normal tissue is applicator in position • High shielding required
negotiated by • Outpatient procedure • Due to short time available and
(1) Fractionation • Can treat large number of patients complex procedure, error prone
(2) Adequate separation between • Multiple treatment fractions are
source and normal tissue required
• High cost and more human
resources required
137
Medium dose rate 2–12 Gy/h Cs • Results have shown inferior
(MDR) results
• Not used in routine practice
226
Low dose rate (LDR) LDR Ra, • Sufficient time for repair of • Superior radiobiological effect Prolonged treatment time and bed
137
0.4–2 Gy/h Cs sublethal damage • Predictable clinical effects rest
• Tumour cells are preferentially • Minimum intersession variability in LDR sources is less manufactured
killed compared to normal tissue dose distribution Radiation exposure to staff
• Overall treatment time is shorter, • Practised since long time
prevents accelerated repopulation
125
Ultra LDR I, • Reassortment of tumour cells into
103
0.01–0.3 Gy/h Pd radiosensitive G2M phase during
treatment
• Acute hypoxia gets corrected
during treatment and oxygen
enhancement ratio is lower for
LDR than for HDR
192
Pulse dose rate (PDR) One pulse per I • Radiobiological advantage similar • Radiobiological advantages of LDR • More expensive than LDR,
hour to LDR • Better dose distribution by maintenance difficult
One pulse of optimization • Less utility in high volume centre
~70 c • Minimal radiation exposure for patient • Caution while dose conversion
Gy × 39–40 • Radiation free interval for patient from LDR to PDR
pulses, to a • Compensation for source decay by
dose of widening the hourly pulses, keeping
28–30 Gy the overall treatment time and average
dose rate fixed
V. R. Anjali
16 Basics of Brachytherapy and Common Radio Nucleotides 105

16.2.1.2 Negatron Emission fluorescent X ray (internal photo electric effect)

• Beta minus decay. or Auger electrons. For higher atomic numbers,
• High neutron to proton ratio in nucleus. fluorescent yield will be predominant.
• Neutron changes to proton by emitting nega- • E.g. 125I.
tive electron and antineutrino.
• Atomic number increases by one. 16.2.1.7 Internal Conversion
• E.g. 15P32 → 16 S 32 + e− + γ + antineutrino. • When the nucleus is in unstable state, losses
its energy by emission of gamma energy. This
16.2.1.3 Positron Emission excess nuclear energy is transferred to orbital
• Beta plus decay. electron, which acquires energy and gets
• High proton to neutron ratio in nucleus. ejected from the shell (internal photoelectric
• Proton changes to neutron by emission of pos- effect). The vacancy is filled by outer orbital
itron and neutrino. electron with production of characteristic pho-
• Atomic number decreases by one. ton or auger electron.
• E.g. 11Na22 → 10 Ne 22 + e+ + γ + neutrino.
Radionuclide is classified according to the
16.2.1.4 Gamma Decay radiation emitted.
• Usually after electron capture or beta decay,
the daughter nuclei in excited state will emit • Pure beta emitter—H-3, P-32, Sr-90, Y-90,
excess energy as gamma rays instantaneously Ru-106.
and attain stable state. • Pure gamma emitter—Cr-51, Fe-55, Co-57,
• E. g.: 27 Co 60 → 28Ni 60 + β + γ (1.33 MeV, Tc-99m, I-125.
1.25 MeV). • Gamma and beta emitters—Na-24, Co-60,
I-129, I-131, Xe-133, Au-198.
16.2.1.5 Isomeric Transition • Positron emitter—F 18.
• After undergoing radioactive decay by parent • Alpha and gamma emitter—Ra-226, Rn-222,
atom, the daughter nucleus remains excited Am 241.
for reasonable time. The excited state of • Neutron emitter—Cf 252 (Fig. 16.1).
daughter nucleus is called metastable state.
Later they emit energy and attain stable state.
The final product formed will have same 16.3 Sealed Radionuclide
atomic number and mass number as that of
metastable isomer but with different energy 16.3.1 Radium 226 (Ra 226)
level.
• E.g. 99Mo (67 h) → 99m Tc (6 h) + −1β0 → • Discovered by Marie Curie in 1898.
99Tc + γ. • Isolated from pitchblende ore.
• Decays by alpha decay to Radon 222 and
16.2.1.6 Electron Capture finally to stable lead.
• Unstable nuclei with high proton to neutron • Half-life—1622 years.
ratio, and atom does not have sufficient energy • Gamma energy—0.83 MeV
for positron decay, it captures orbital electron (0.184–2.45 MeV).
into nucleus and convert proton to neutron to • Maximum energy of beta rays—3.26 MeV.
gain stability. Usually K-shell electrons are • HVL—14 mm of lead.
captured known as K capture. • Available as cell, tubes, needles.
• Vacancy created in K shell is filled by outer • Used in interstitial, intracavitary, and mould
orbital electron, with release of characteristic/ brachytherapy.
106 V. R. Anjali

RADIONUCLIDE

SEALED SOURCES UNSEALED SOURCES

• Radioactive material will be contained in a solid • Unsealed radionuclide is not contained in a

material and encapsulated, once or twice in a container.
stainless-steel container. • Usually available in liquid form.
• This metal housing absorbs the beta particle. • When given orally or intravenously they localise
• This also provides physical strength to the source. to the target tissue by virtue of its biological,
• E.g. Co 60, lr192, Ra 226, Cs 137, Au198, I 125, Pd physical or chemical property.
103... • E.g. I 131, P-32, Sm153, Sr-89, Ra-223, Re-
186, Re 188.

Fig. 16.1 Types of radio nucleotides

16.3.2 Cobalt 60 16.3.4 Cesium 137 (Cs 137)

• Naturally occurring as stable Co-59. • Naturally occurring as stable 55Cesium 133.

• Cobalt-60 is produced by the neutron activa- • Produced by nuclear fission of Uranium-235.
tion of stable cobalt (Co 59). • Decay scheme: 55137 Cs → 13756Ba +
• Decay scheme: 6027Co → 6028Ni + −1 0-1e + γ
0e + y. • Half-life—30.22 years.
• Half-life–5.26 years. • Monoenergetic gamma ray
• Gamma energy—1.173 MeV and 1.333 MeV emitter—0.662 MeV.
(average—1.25 MeV). • Beta energy—0.51 MeV.
• Beta energy = 0.318 MeV • HVL—5.5 mm of lead.
• HVL—10 mm of lead. • Available as tubes, needles, pellets, miniature
• Available as pellets, needles, slug. source.
• Used in intracavitary brachytherapy, telether- • Used in intracavitary brachytherapy.
apy, plaque brachytherapy. • Radioactive Cesium chloride is hygroscopic
and highly dispersible.

16.3.3 Iridium 192

16.3.5 Gold (Au 198)
• Naturally occurring as 77 Ir 192 and 77 Ir193.
• Iridium 192 produced by neutron activation in • Naturally seen as stable gold197.
nuclear reactor. • Gold 198 is produced by irradiation of thermal
• Decays by beta emission (95%) to platinum 192 neutrons Au197.
and by electron capture (5%) to osmium 192. • 79Au197 + 0n1 → 70Au198 + γ
• Half-life 73.83 days. • Gold decays to form stable mercury by emis-
• Gamma energy—0.380 MeV (0.136–1.06 sion of beta and gamma particle.
MeV). • Half-life—2.7 days.
• Beta particle energy −0.670 MeV. • Gamma energy—0.412 MeV.
• HVL −4.5 mm of lead. • Beta energy maximum of 0.960 MeV.
• Available as seeds, wires, hairpin, ribbon, • HVL 2.5 mm of lead.
slugs, miniature source. • Available as gold grains encapsulated in plati-
• Used in intracavitary, interstitial, and intravas- num capsule.
cular brachytherapy. • Permanent brachytherapy implant.
16 Basics of Brachytherapy and Common Radio Nucleotides 107

16.3.6 Iodine 125 (I 125) and Y-90 m.

• Yttrium 90 decays by emitting beta rays
• Produced from Xenon 124and its isotope by (2.27 MeV) to stable zirconium90.
neutron capture. • Beta energy—546 keV.
• Decays by electron capture to 125Telleurium. • Half-life—28.2 years.
• 125I + e− → 125Te + γ • Half-value layer: 0.14 mm lead.
• T1/2 = 59.4 days (60 days). • Used in plaque and intravascular brachyther-
• Emits gamma rays with average energy of apy (Table 16.2).
28 keV (27–31 keV).
• Half-value layer: 0.025 mm Pb.
• Available as seeds. 16.4 Unsealed Radionuclide
• Used for permanent interstitial and plaque
brachytherapy. 16.4.1 Iodine 131 (I 131)

• Produced from nuclear fission of uranium atom.

16.3.7 Palladium (Pd 103) • Decays by beta minus decay to xenon.
• Half-life—8 days.
• Produced by neutron bombardment of • Emits gamma rays of 364 keV.
Palladium 102. • Emits beta rays of 600 keV (250–800 keV).
• Decays by electron capture to Ruthenium-103. • HVL—3 mm lead.
• 103Pd + e− → 103Rh + γ • Iodine 131 is taken up by differentiated fol-
• Half-life is 17 days. licular thyroid tissue and concentrates it 6.6
• Average gamma energy—21 KeV times more than other body tissue.
(20–23 KeV).
• Half-value layer—0.004 mm of lead.
• Available as pellets, seeds. 16.4.2 Phosphorus 32 (P 32)
• Used in permanent interstitial brachytherapy.
• Produced by irradiating Sulphur 32 with fast
neutrons.
16.3.8 Strontium 90 (Sr 90) • S 32 + n → P 32 + p.
• Decays by beta decay to S-32.
• Produced by thermal fission of uranium 235. • Pure beta emitter.
• Pure beta emitter which decays to yttrium90 • Maximum energy—1.71 MeV.

Table 16.2 Summary of commonly used sealed radio nucleotides

Element Half-life Energy (MeV) Exposure rate constant (mCi−1 h−1)
Radium (Ra226) 1626 years 0.83 8.25
Cesium (Cs137) 30 years 0.662 3.28
Iridium (Ir 192) 73.8 day 0.38 4.69
Cobalt (Co60) 5.26 years 1.25 13.07
Iodine (I 125) 60 days 0.028 1.45
Palladium (Pd 103) 17 days 0.021 1.48
Gold (Au 198) 2.7 days 0.412 2.35
Strontium (Sr 90) 28.9 years 0.546 (β) –
Americium (Am 241) 432 years 5.48 (α) 0.12
0.060 (γ)
Californium (Cf 252) 2.65 days 2.4 (n) –
Cesium (Cs 131) 9.69 days 0.030 0.64
108 V. R. Anjali

• Average energy—0.70 MeV. • White vinegar can be an effective decontam-

• Half-life: 14.3 days. ination solvent for this nuclide in most
• Aqueous form used in treatment of CML, forms.
polycythaemia vera.
• Colloidal form in malignant pleural and peri-
cardial effusion. 16.4.3 Radium 223 (Ra 223)
• Intraperitoneally used in ovarian cancer.
• Shielding is done with low density material • Produced artificially by irradiating radium
like plexiglass, acrylic, Lucite, wood. 226 with neutron.
• High density material results in bremsstrah- • Radium 223 is prepared from radium 226 by
lung production. “milking” it from actinium 227.

Ra 226 + on1 → Ra 227 → Ac 227 → Th 227 → Ra 223
42 min 21.8 years 18.7 days

• Half-life—11.43 days. • Phase III trial ALSYMPCA showed overall

• Emits alpha particle (95.3%) energy of survival in patients with CRPC with symp-
5–7.5 MeV. tomatic bony metastasis.
• Beta particle (3.6%) energy of 0.45 MeV. • Dose is 50 kBq per kg body weight, at 4 weeks
• Gamma particle (1.1%) energy of interval for 6 cycles.
0.01–1.27 MeV. • When given intravenously Radium 223 di chlo-
• Range of alpha particle<100 micrometre. ride mimics calcium and forms complexes with
• Approved by FDA in May 2013 for hydroxyapatite and target bone metastasis.
castration-­
resistant prostate cancer with • Side effects: thrombocytopenia, diarrhoea,
symptomatic bone metastasis with no vis- vomiting, nausea, bone fracture, pancytope-
ceral metastasis. nia, neutropenia (Table 16.3).

Table 16.3 Summary of commonly used unsealed radio nucleotides

Half-life Energy
Unsealed radionuclide α β γ
Iodine (I 131) 8 days – 190 keV 346 keV
Phosphorus (P 32) 14.3 days – –
Strontium (Sr 89) 50.5 days – 0.583 MeV –
Samarium (Sm-153) 46.3 hours – 0.23 MeV 103 keV
Radium (Ra-223) 11.4 days 6 MeV 330 keV 270 keV
Rhenium (re-188) 17 hours – 2.1 MeV 155 keV
 Brachytherapy in Carcinoma
Cervix 17
Prashanth Giridhar and Goura K. Rath

The chapter is divided in the following 17.1.1 MUPIT (Fig. 17.2)

headings:
• Can be used for cervix, vulva, urethra, pros-
1. Applicators in gynaecological brachytherapy tate and rectal interstitial brachytherapy. It is
2. Intracavitary brachytherapy (carcinoma therefore called universal template
cervix) • The angled needles can cover up to 7 cm of
(a) Patient selection and indications parametrium
(b) Procedure • The inner table is sutured to perineum with
(c) Contouring for MR brachytherapy stay sutures
3. Interstitial brachytherapy (carcinoma cervix)
(a) Patient selection and indications
(b) Procedure 17.1.2 Applicators in Cervix
4. Ultrasound in gynaecological brachytherapy Intracavitary Brachytherapy
5. Evolving role of Doppler in gynaecologic
brachytherapy Modified Fletcher-Suit applicator (Fig. 17.3):

• Commonly used ICRT applicator

17.1 Applicators for Cervix • Ovoid of various sizes available to fit properly
Interstitial Brachytherapy in vagina
• The flange has adjustable lock to be placed for
Venezia Applicator (Fig. 17.1): different intrauterine lengths
• Only CT compatible
• Recently launched by Elekta
• Applicator can be used for intracavitary, inter- MR compatible intracavitary applicator
stitial and intravaginal brachytherapy in cervi- (Fig. 17.4a):
cal cancers
• Adds a unique insertion tool to place needles • MR compatible applicator is thicker in size
at exact depths allowing better preplanning and therefore difficult for placement in steno-
sis of cervical OS (requires more dilatation)
P. Giridhar (*) · G. K. Rath and vagina
Department of Radiation Oncology, National Cancer • Can be used in CT based reconstruction as
Institute, All India Institute of Medical Sciences, well
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 109

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_17
110 P. Giridhar and G. K. Rath

VENEZIA APPLICATOR

One-click system
for easy assembly

22, 26, 30 mm sizes

present
MR
Two lunar-shaped avoids compatible
form a ring when clicked
together
Tandem

Integrated
cervical
stopper

Insertion tool
present to
place needles
at exact depths

Space for TRUS

probe

Cylinder caps
alow treatment
Perineal templates
of the voginal wall
for reaching
vaginal extensions
Ovoid holes allow
parallel and oblique
needles to reach
the parametrium

Fig. 17.1 Venezia applicator for cervix interstitial brachytherapy

Martinez universal perineal interstitial template

Fixing Screw for the Cylinder or Circular Insert

Inner template Outer template Angle

between
parallel and
angled
needles is 13
degree
Circular
insert

Cylinder

Outer plate to fix

with inner plate to
prevent Note the hole in
Slots for
displacement of obdurator. Used for
needles
Space for needles placing tandem if
Assemnbled
screw to Slot for needles cervical os is
Fixing Circular insert if MUPIT showing
fix outer negotiable
screw vaginal stenosis obdurator, needles,
and inner Obdurator
Slot for obdurator or rectal present and inner and outer
plate
catheter based on positioning of obdurator cannot template
template be placed

*Template is made of plastic material and materialneeds to be handled with care as risk of bending or cracking the templates present

Fig. 17.2 MUPIT applicator for cervix interstitial brachytherapy

17 Brachytherapy in Carcinoma Cervix 111

Fig. 17.3 Modified Modified Fletcher Suit Applicator

Fletcher-Suit applicator Lock Stainless steel
material
Ovoids

Tandem

Flange
15, 20, 25
30 mm sizes
Rectal and bladder shielding removed ovoids
Lock
Used for HDR brachytherapy in Cervical cancers

Fig. 17.4 (a) MR a Fletcher Suit MR compatible applicator

compatible intracavitary
applicator, (b) Vienna Note that the
ring applicator applicator is Occupies more Carbon fibre material
thicker than CT space in vagina
Lock Ovoid of 15, 20,
compatible
applicator 25, 30, 35, 40
mm size present
Flange or
cervical
Lock
stopper

Tandem 15
and 30
Note that unlike the CT compatible degree
Fletcher applicator, the ovoid is fixed present
just below the flange in this applicator

b Vienna Ring applicator MR compatible

Carbon fibre
Lock Upto 9 needless can be placed

Interstitial
needles - ONLY
parallel
Ring with holes
Lock for needles
present of 26, 30,
34 mm size
Tandem of
20, 40, 60
mm length
*Note that its a fixed geometry present
applicator with locks at fixed
distance on the tandem. Tandem
Provides less maneuverability angle is 60
and difficult to place in short and degree
stenosed vagina
112 P. Giridhar and G. K. Rath

Utrecht CT/MR interstitial applicator Rotterdam Cervix applicator

Uses Ovoids as Made of titanium Fixed geometry

template for applicator. Easily
interstitial needles inserted if smit
sleeve is in situ

Has insertion tool Additions for

to guide depth of treating vaginal
needle placement extensions

Fletcher Williamson Cervix applicator

Henschke Cervix applicator

Has in built rectal Made of titanium

and bladder shield

Fig. 17.5 Applicators used for intracavitary brachytherapy in carcinoma cervix

be taken for applicator placement under mild

Vienna ring applicator (Fig. 17.4b): sedation and analgesia or under spinal anaesthe-
sia. We personally prefer using spinal anaesthesia
• It has 2 locks placed at fixed distances making due to three reasons:
placement difficult in short vagina
• The angle of the ring is also fixed
• Only parallel needles can be placed and so the 1. Pelvic muscle relaxation leading to better
lateral throw into parametrium is less manoeuvrability and easier placement of
applicators
Other applicators are shown in Fig. 17.5. 2. Good analgesia during applicator placement
and treatment leading to more patient compli-
ance for subsequent sessions
17.2 Intracavitary Brachytherapy 3. Minimal voluntary movement of lower limbs
(ICRT) in Cervix decreases risk of displacement of applicators

Patient Selection All patients undergoing exter- Spinal anaesthesia has the following risks (spe-
nal beam radiotherapy for carcinoma cervix cific to carcinoma cervix patients):
should be evaluated for intracavitary brachyther-
apy. Examination of supraclavicular fossa, ingui- 1. Prolonged immobilization may lead to higher
nal region and per speculum/vaginum needs to be risk of deep vein thrombosis (cancer being
done to ascertain extent of disease. Patients may thrombophilic)
17 Brachytherapy in Carcinoma Cervix 113

2. Full analgesia may make it difficult to detect 10. Ovoids or ring of largest possible size placed
vaginal tears and uterine perforations early in vagina at the level of flange
during the procedure 11. The applicator locks are placed
12. Initial posterior packing behind the ovoids or
ring to decrease rectal dose followed by
17.2.1 T
 umour Specific Criteria anterior packing to decrease bladder dose
for Patient Selection of ICRT done

1. No vaginal stenosis
2. Os negotiable 17.2.4 C
 ontouring for MR Guided
3. Tumour size <4 cm (i.e. 2 cm on either side of Brachytherapy
os) at time of ICRT
4. No or minimal parametria extension at the 1. Pre-RT MR imaging is ideal for imaging of
time of ICRT the primary cervical disease. Evaluation of the
5. No involvement of lower vagina vagina can be optimized by inserting vaginal
6. No adjacent organ involvement contrast, such as gel.
2. Information on clinical examination is also
helpful in addition to MRI
17.2.2 P
 atient Specific Criteria 3. A pelvic surface improves resolution of the
for Patient Selection of ICRT MR imaging.
4. Ideal time for MR imaging for BT contouring
1. Normal hemogram and prothrombin time is while the BT applicators are in situ.
2. Patient can be placed in lithotomy position or 5. GEC-ESTRO recommends MRI imaging for
at least with lower limb abducted and exter- BT in 3 T2WI planes [fat saturation is not
nally rotated >30 degrees required]—axial, coronal and sagittal
6. Advantage of T2 images—even with treat-
ment tumour shows intermediate to high sig-
17.2.3 Procedure nal intensity
7. Enlarging pelvic lymph nodes could be a sign of
1. Patient placed in lithotomy position after disease. Some of the lymph nodes after EBRT
anaesthesia/analgesia undergo cystic necrosis and may have the appear-
2. Cleaning of perineum done ance with multiple cysts [similar to ovary].
3. Two-way Foley catheter placed in bladder
and 7 mL of diluted (2 mL contrast and 5 mL
water) contrast placed in bulb 17.3 Interstitial Brachytherapy
4. Draping of perineum done (Carcinoma Cervix)
5. Transrectal ultrasound (TRUS) used
(Fig. 17.1) to identify a. Uterine position— 17.3.1 Patient Selection
Retroverted versus anteverted; b. Presence or and Indications
absence of pyometra; c. Approximate length
of uterus 1. Vaginal stenosis present
6. Uterine sound placed through os to confirm 2. Os not negotiable
the length of uterus 3. Tumour size >4 cm (i.e. >2 cm on either side
7. Hegar dilator used to dilate cervical os for of os) at the time of brachytherapy
placement of tandem 4. Parametria extension at the time of
8. Tandem of appropriate length placed such brachytherapy
that it reaches the uterine fundus 5. Involvement of lower vagina present
9. TRUS used to confirm placement within 6. Adjacent organ involvement present at
uterus baseline
7. Normal hemogram and prothrombin time
114 P. Giridhar and G. K. Rath

8. Patient can be placed in lithotomy position or 12. Finally, the posterior needles (perirectal) are
at least with lower limb abducted and exter- placed and position confirmed with TRUS
nally rotated >30° and clinical P/R
13. Stoppers are placed over all needles now to
prevent inward displacement of needles
17.3.2 Pre-procedure Checklist 14. Outer plate is placed and screws are placed
15. Stoppers are placed again on needles to pre-
1. Physical examination to check vaginal steno- vent outward displacement of needles
sis, adjacent organ involvement and extent of 16. Check is made for haematuria or fresh bleed
parametria involvement and rule out progres- P/R
sive disease 17. Patient shifted to recovery room
2. Pre-brachytherapy imaging check (ideally
MRI) to look at the extent of disease and rule
out progressive disease 17.3.4 Special Scenario
3. Pre-brachytherapy TRUS to check the depth
of needle placement required during proce- 1. If os not negotiable: Tandem not placed and
dure and organ involvement (if any) dose coverage achieved with interstitial
needles
2. If complete vaginal stenosis: Obdurator not
17.3.3 Procedure (MUPIT Applicator) placed. Inner plate closed with circular insert
as shown in figure
1. Patient placed in lithotomy position after 3. If adjacent organ involvement: Needles are
combined spinal epidural anaesthesia placed in bladder or rectum to achieve ade-
2. Cleaning of perineum done quate dose. Patients to be monitored for bleed-
3. Three-way Foley catheter placed in bladder ing which is usually self-limiting or settles
and bulb inflated with conservative measures
4. Draping of perineum done
5. Transrectal ultrasound (TRUS) used (Fig. 17.2)
to identify (a) Adjacent organ involvement; (b) 17.4 Ultrasound
Parametria extent; (c) Doppler if available can in Gynaecological
be used to identify major vessels in the area of Brachytherapy
implant to reduce risk of bleeding
6. If there is no vaginal stenosis, the length of Transrectal ultrasound is routinely used in pros-
vagina is measured with obdurator. The inner tate brachytherapy but less commonly used in
template of MUPIT is then fixed with cervix brachytherapy. This section will deal in
obdurator brief with advantages of TRUS, interpretation of
7. If cervical os is negotiable, place tandem TRUS images to understand the extent of disease
with TRUS guidance and evolving role of Doppler in cervical cancer.
8. The obdurator is placed in vagina with tan- Advantages of TRUS guidance in cervix
dem within it and inner plate is sutured to brachytherapy:
perineal skin
9. With guidance of pre-BT MRI images and 1. Accessibility in the operating room is high
TRUS, interstitial needles are placed at 2. Real-time image guidance during insertion is
required depths possible
10. Initially the anterior (periurethral needle) is 3. Catheter and target visualization is high
placed due to two reasons: (a) Reduce chance
of acoustic shadow hampering further needle Figure 17.6 shows sagittal views of TRUS for
placement; (b) Save the Foley bulb from get- defining the extent of disease. Once the extent of
ting ruptured disease is defined, interstitial implant can be done
11. The parametria (lateral) needles are placed next following the steps explained earlier.
 17 Brachytherapy in Carcinoma Cervix

Sagittal san (0º) of normal anatomy. 1 = rectum, 2 = anterior wall of the rectum,
3 = posterior wall of the vagina, 4 = anterior wall of the vagina, 5 = posterior wall of the blad- Sagittal san (0º) of stage IB cervical carcinoma. 1 = rectum, 2 = anterior wall of the
der, 6 = bladder, 7 = posterior lip of the cervix, 8 = anterior lip of the cervix, 9 = cervical ca- rectum, 3 = vagina, 4 = rectovaginal space, 5 = posterior wall of the bladder, 6 = bladder, 7 =
nal, 10 = posterior fornix, 11 = anterior fornix. cervix, 8 = nodular hypoechoic neoplasm that is distinct from the normal cervical stroma.

Lateral san (45º) of normal anatomy.1 = rectum,2 = anterior wall of the rectum,
3 = parametrium,4 = areolar connective tissue, 5 = bladder, arrowheads = parametrial vas-
cular structures. Lateral san (60º) of stage IIB cervical carcinoma.1 = anterior lateral wall of the
rectum, 2 = neoplastic involvement of the distal parametrium,3 = areas of gaseous necrosis

*Paulo innocenti et al; Staging of Cervical cancer: Reliability of Transrectal ultrasound (TRUS) published in Radiology 1992

Fig. 17.6 Imaging features of TRUS in cervical cancer: (A pictorial depiction∗). The Cervical cancer usually is not distinguishable from normal cervical stroma and is hypo
images shown below depict sagittal views of TRUS for defining the extent of disease. or isoechoic. The images shown depict normal structures as well as early and locally
advanced cervical cancer [1]
115
116 P. Giridhar and G. K. Rath

Superior Inferior

Fig. 17.7 Vessel size and distribution on Doppler USG

Courtesy *Rajni Sethi et al; Real time DOPPLER ultrasound to identify vessels and guide needle placement for gynaecologic
interstitial brachytherapy; Brachytherapy 2018

Fig. 17.8 The use of real-time Doppler ultrasound to identify vessels to guide needle placement in interstitial
brachytherapy

17.5  merging Role of Doppler

E • Figure 17.8 shows use of real-time Doppler
in Cervix Brachytherapy [2] ultrasound to identify vessels during intersti-
tial brachytherapy.
• Bleeding although rare is a potential fatal
complication of interstitial brachytherapy
• The addition of Doppler to the TRUS allows
identification of vessels as the needle is being References
inserted and thus reduces the risk of bleeding
• Newer TRUS probes have Doppler capability 1. Innocenti P, Pulli F, Savino L, Nicolucci A,
Pandimiglio A, Menchi I, et al. Staging of cervical
and are thus useful cancer: reliability of transrectal ultrasound (TRUS)
• Puncture of cervical vessels can cause intra- published in. Radiology. 1992;185(1):201–5.
vaginal bleed and puncture of paracervical 2. Sethi R, Kuo YC, Edraki B, Lerner D, Paik D,
vessels may lead to fatal intraperitoneal Bice W. Real-time Doppler ultrasound to identify
vessels and guide needle placement for gynaeco-
haemorrhage. logic interstitial brachytherapy. Brachytherapy.
• Figure 17.7 shows vessel size and distribution 2018;17(5):742–6.
on Doppler USG3
 Brachytherapy in Head and Neck
Cancers 18
Supriya Mallick and Goura K. Rath

Brachytherapy in head and neck cancer can be 18.2 Pre-brachytherapy

used as definitive modality alone or as boost in Evaluation
patients with larger tumors. Brachytherapy can
also be used as salvage modality especially 1. Local imaging: MRI provides better soft tis-
in localized recurrence. Brachytherapy may also sue delineation and hence should be preferred
be used in setting of re-irradiation due to the con- to estimate the extension (particularly impor-
formal distribution in sites like nasopharynx. tant for oral tongue), CECT of face with
Exophytic lesions do better than infiltrative puffed cheek maneuver in important for carci-
type of lesions with brachytherapy. A potential noma buccal mucosa.
advantage of brachytherapy over EBRT alone is 2. Mouth opening: Patient should have at least
better organ preservation due to higher biologi- three finger wide mouth opening to allow bet-
cally equivalent dose that can be delivered [1]. ter visualization and provide access to the site
One of the potential limitations for its use as a of interest.
sole modality is inability to treat nodes, so radical 3. Dental prophylaxis: As patients will require
radiotherapy alone must be used only in patients self retaining retractor patients should be eval-
with a low chance of nodal spread. Another uated for any loose teeth and an extraction of
potential demerit is the invasive nature of the pro- such teeth should be performed at least 7 days
cedure, pain associated, and the need for anesthe- prior to the procedure. Proper management of
sia during procedure. The key to success to head dental hygiene should be done.
and neck brachytherapy protocol is proper patient 4. Patients with short neck, intervertebral disc
selection. prolapsed, or vertebral column disorder
should be carefully selected as it may become
difficult for the procedure.
18.1 Indications [2] 5. A nasal intubation is always preferred as it
gives better visualization.
The indications for brachytherapy in head and 6. A pre-procedure tracheostomy may be
neck cancers and outcomes are summarized in required for patients with primary in base or
Table 18.1. posterior tongue.
7. In patients with tumors of the posterior part of
the oral cavity and oropharynx, an examina-
S. Mallick (*) · G. K. Rath tion under general anesthesia is necessary.
Department of Radiation Oncology, National Cancer This should be done in combination with
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 117

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_18
118 S. Mallick and G. K. Rath

Table 18.1 Indications for head and neck brachytherapy and outcomes
Site HDR dose Patient selection Result
Oral cavity Radical 40–44-4 Gy T1/early T2 N0 lesions 80–90% local control
in 4 Gy per # Avoid in lesions of tip of tongue/<5 mm
from mandible
Boost 16–20 Gy in When node positive disease has shrunk/
4 Gy per # when upfront brachytherapy is possible
Oropharynx Boost 16–20 Gy in Technically challenging 90% local control for
4 Gy per # T1/early T2 N0 lesions T1/2 lesions
Contraindicated when tumor extends to
retromolar trigone, the nasopharynx, the
larynx, the hypopharynx
Nasopharynx Salvage 60 GY LDR Residual disease/ relapse must be 82% local control for
Boost 12–18 Gy in 1. Tumor <1 cm thick T1/2 lesion when
three fractions 2. Not infiltrating bone/ITF Brachy used in boost
3. Not extending to nasal cavity/oropharynx

­ anendoscopy to rule out synchronous second

p tongue a hyperextended neck should be
primary tumors. considered.
8. In patients with primary in lip, oral tongue, 3. Nasal intubation is preferred.
floor of mouth, and buccal mucosa a 3–5 mm 4. A laryngeal gauge should be placed to avoid
thick lead spacer should be used to reduce the aspiration of blood or water.
dose to the mandible and prevent necrosis. 5. Self retaining retractor should be placed in
However, this lead may produce secondary opposite angle of mouth.
electron and induce more mucositis. 6. A stay suture may be considered for carci-
Therefore, it should be coated with plastic or noma oral tongue.
latex. 7. A Ryles tube should be placed before comple-
tion of the procedure.
8. Catheters should be placed at least in two
18.3 Absolute Contraindication planes; catheters should be parallel and equi-
distant; and ideally spaced at 1–1.5 cm from
1. Large locally advanced tumor. each plane and each catheter. Figure 18.1
2. Moderate to extensive sub-mucosal fibrosis as shows brachytherapy catheter placement for a
it reduces mouth opening. patient with carcinoma of the buccal mucosa.

18.4 Relative Contraindication 18.6 Target Definition

1. Short neck: as it becomes difficult to position 1. The GTV should be delineated carefully. It
the patient with neck hyperextended. should incorporate the visible tumor and any
2. Deviated nasal septum/nasal synechiae/ palpable induration. The prior radiological
pathology that interferes with nasal inputs must be considered for GTV
intubation. delineation.
2. The CTV should incorporate the entire GTV
with an isotropic expansion of 5–10 mm.
18.5 During the Procedure 3. In “Perfect” implant the CTV should be con-
sidered as the PTV.
1. Head ring should be used to stabilize the head. 4. The skin should not be considered in the target
2. For buccal mucosa a later position is preferred volume and attention should be paid during
and in oral tongue, floor of mouth, base of source loading.
18 Brachytherapy in Head and Neck Cancers 119

Fig. 18.1 Brachytherapy catheter placement for buccal mucosa, floor of mouth, and oral tongue

Fig. 18.2 2D X-ray based and CT based planning in patients with head and neck brachytherapy

18.7 Dose and Plan Evaluation 5. As boost the dose may be 16–20 Gy @ 4 Gy
per fraction. Whenever, brachytherapy is
1. According to GEC-ESTRO doses between 3 being used as boost it should follow EBRT.
and 4 Gy per fraction should be used. 6. The entire PTV should be well covered by
2. Radiation should be delivered twice a day, the 100% isodose line.
interval between fractions should be as long 7. Volume receiving 200% of prescription dose
as possible, with a minimum of 6 h. should not exceed 15–18% of the target volume.
3. In definitive setting a HDR dose of 40–44Gy 8. According to ABS the total duration
@ 4 Gy per fraction, twice daily at least 6 h (EBRT + Brachytherapy) should not exceed
apart may be used. 8 weeks. Figure 18.2 shows 2D X-ray and CT
4. It is advisable to start the treatment on Monday based planning for head and neck
avoid gap in the weekend. brachytherapy.
120 S. Mallick and G. K. Rath

18.8 Catheter Removal Source of Images The image was taken from a
patient treated by authors as per hospital protocol
1. Catheter removal should be done with great and consent was taken.
care as there are chances of bleeding and
aspiration.
2. It should be done in operating room with ade- References
quate preparedness for sudden bleeding and
1. Quon H, Harrison LB. Brachytherapy in the treatment
airway management.
of head and neck cancer. Oncology (Williston Park).
3. At least two persons should be available. 2002;16(10):1379–96.
4. In case of bleeding bimanual pressure for 2. Kovács G, Martinez-Monge R, Budrukkar A, Guinot
5–10 min should be sufficient, otherwise fig- JL, Johansson B, Strnad V, et al. GEC-ESTRO ACROP
recommendations for head & neck brachytherapy in
ure of eight suturing may be required.
squamous cell carcinomas: 1st update: improvement
5. The end of the catheter should be secured by cross sectional imaging based treatment planning
with tooth forceps first as the catheter head and stepping source technology. Radiother Oncol.
may plunge in the edema. The catheters 2017;122(2):248–54.
should be cut from the distal end. Care
should be taken to minimize the travel of the
catheter through the tissue to reduce
infection.
 Prostate Brachytherapy
19
Prashanth Giridhar and Aruna Turaka

19.1 Patient Evaluation 19.2 Absolute Contraindications

1. Pre-treatment AUA/IPSS scores and baseline 1. Presence of rectal fistula

colonoscopy 2. Anesthetic contraindications
2. Pre-treatment sexual evaluation—SHIM score 3. Contraindications to LDR brachytherapy are
3. History of prior pelvic radiation/previous uro- summarized in Table 19.2.
logic surgery—brachytherapy to be done only
more than 3 months of TURP/TUIP and ure-
thral dose constraint should be kept less than 19.3 Pre-procedure Patient
110% of prescribed dose Preparation
4. History of rectal surgery can lead to difficulty
in TRUS evaluation and also recurrent rectal 1. Anesthetic check-up and clearance obtained
cancer to be ruled out before procedure
5. History of inflammatory bowel disease— 2. Rectal preparation—Proper bowel prepara-
brachytherapy should be done in carefully tion is critical and patient must take polyethyl-
selected asymptomatic patient who is not on ene glycol 48 h and 24 h prior to the procedure.
active treatment for last 6 months or more Additional laxatives and enema may be given
6. Patients evaluation for bony pelvic defects if needed before the procedure.
and ability to position in lithotomy position
7. The ESTRO/EAU/EORTC with recommen-
dations on patient selection for LDR brachy- 19.4 LDR Brachytherapy
therapy are shown in Table 19.1
8. Neoadjuvant androgen deprivation therapy 19.4.1 E
 quipment Required for LDR
(ADT) may be used in patients with large pros- Brachytherapy
tate prior to brachytherapy to reduce its volume.
1. A transrectal ultrasound (TRUS) probe (high
resolution between 5 and 12 Mhz) with dedi-
P. Giridhar cated prostate brachytherapy software. The
Department of Radiation Oncology, AIIMS, TRUS should have sagittal and transaxial
New Delhi, India
visualization
A. Turaka (*) 2. Stepping unit support system containing a
Paramount Oncology Group (POG), Wendt Regional
Cancer Centre, Dubuque, IA, USA cradle to hold the ultrasound probe and
e-mail: arunaturaka@gopog.com allow three-dimensional movement and can

© Springer Nature Singapore Pte Ltd. 2020 121

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_19
122 P. Giridhar and A. Turaka

Table 19.1 ESTRO/EAU/EORTC recommendations for indications on LDR brachytherapy [2]

Recommended (do well) Optional (fair) Investigational (poor outcome)
PSA (ng/mL) <10 10–20 >20
Gleason score 5–6 7 8–10
Stage T1c-T2a T2b-T2c T3
IPSS 0–8 9–19 >20
Prostate volume (g) <40 40–60 >60
Qmax (ml/s) >15 15–10 <10
Residual volume (cm3) >200
TURP +

Table 19.2 Contraindications to LDR brachytherapy, as recommended by ABS and ESTRO/EAU/EORTC

ABS guidelines [1]
Absolute Relative ESTRO/EAU/EORTC guidelines [2]
 • Limited life expectancy  • High IPSS >20  • Life expectancy less than
 • Unacceptable operative risks  • History of prior pelvic 5 years
 • Distant metastases radiotherapy  • Metastatic disease
 • Absence of rectum, precluding the  • TURP defects  • Recent TURP with persisting
use of TRUS  • Large median lobes large defect
 • Large TURP defects  • Prostate gland >60 cm3 at  • Bleeding disorder
 • Ataxia telangiectasia implantation  • Prostate gland >50cm3 at
 • Inflammatory bowel disease implantation

be mounted on the operating table or on the 19.4.3 Procedure of LDR

ground Brachytherapy
3. Perineal template—matched to the grid dis-
played on the ultrasound image and fixed onto 19.4.3.1 Step 1: Volume Delineation
the stepping system TRUS is performed and volumes defined.
4. Implantation needles-18 Gauge around 20 cm Figure 19.1 shows intra-operative TRUS image
long of the prostate
5. Locking/ stabilization needles—optional
6. 3 way Foley catheter and aerated gel (lubricat-
Tumor Volume Definition
ing gel mixed with air)—to visualize the ure- • GTV (Gross tumor volume) is contoured on
thra on TRUS. the pre-implantation TRUS image in and cor-
related with pre-treatment MRI imaging.
Figure 19.2 shows the advantage of MRI over
19.4.2 Techniques for Needle CT for delineation of prostate
Implantation • CTV (Clinical target volume) includes entire
prostate gland with a margin expanded with
1. Preloaded needle technique: done on a pre-­ constraints to the anterior rectal wall and blad-
plan, but can be based on intra-operative plan- der neck:
ning also • T1-2 CTV = visible prostate contour +0.3 cm
2. Free seed technique: uses a Mick applicator or margin
similar device to load the seeds into the • T3 CTV = visible prostate contour + visible
prostate. extracapsular extension +0.3 cm margin
19 Prostate Brachytherapy 123

Fig. 19.1 Intra-operative transrectal ultrasound guided volume study from base to the apex of prostate

Fig. 19.2 Pre-implant

volume study with an
MRI and the difference
in the prostate contours
between MRI and CT
scans

Table 19.3 Recommended doses for brachytherapy based on the NCCN-risk groups
Low-risk group Intermediate-risk group High-risk group Recurrence
LDR brachytherapy alone EBRT + brachytherapy
125
I 145 Gy 145 Gy 110–115 Gy 145 Gy
103
Pd 125 Gy 125 Gy 90–100 Gy 125 Gy
131
Cs 115 Gy 115 Gy 85 Gy 115 Gy

• PTV = CTV • ABS guidelines recommend limiting 1 cc of

• Organs at risk (OAR) defined includes pros- the rectum to 100% of the prescription dose
tatic urethra and rectum (contour the outer (RV 100 < 1 cc) [1]
and inner walls) • Post-implant D90 is generally lower than the
• The prescription doses and various radio-­ pre-plan hence it is important to aim for a
isotopes used for brachytherapy are mentioned higher pre-plan D90
in Tables 19.3 and 19.4. • An intra-operative plan generated for LDR
Brachytherapy is shown in Fig. 19.3
19.4.3.2 Step 2: Pre-plan Generation • ESTRO/EAU/EORTC guidelines for pre-
• The pre-plan dose parameters can be based on plan generation are summarized in
recommendations by international guidelines Table 19.5.
124 P. Giridhar and A. Turaka

Table 19.4 Various isotopes used for permanent prostate brachytherapy

Half-life (days) Avg. energy (keV) Typical monotherapy seed strength
Radionuclide (mCi) (U)
Iodine-125 59.4 28.4 0.3–0.6 0.4–0.8
Palladium-103 17.0 20.7 1.1–2.2 1.4–2.8
Cesium-131 [5] 9.7 30.4 2.5–3.9 1.6–2.5

Fig. 19.3 Intra-operative plan, day 0 (base to the apex)

Table 19.5 Dose parameters pre-plan recommendations 6. Needle insertion

by ESTRO/EAU/EORTC • Start insertion from the anterior row—
GTV GTV >150% minimize TRUS interference
CTV V100 ≥95% • Needle is guided by TRUS transverse
D90 >100% imaging
V150 ≤ 50%
• Needle rotation (tip of the bevel “flashes”
Rectum Primary: D2cc < 145 Gy
Secondary: D0.1cc (Dmax) < 200Gy
up and down)-ensures placement of nee-
Prostatic urethra Primary: D10 < 150% dle at the correct depth
Secondary: D30 < 130% 7. Seed placement—2 methods, the preloaded
technique and the after loading technique
• Preloaded technique—seeds are placed
19.4.3.3  tep 3: LDR Brachytherapy
S
into the needle beforehand
Implant Procedure
• After loading technique—the needles
1. Patient position—dorsal lithotomy position
are positioned in the prostate first, and
2. Perineal template is mounted onto the step-
then seeds are inserted into the needle
ping unit. Concordance with the template
• The seeds are advanced into the intended
grid displayed on the ultrasound image must
position along the needle using the
be ensured
stylet
3. Locking or fixation needles—can be inserted
• Then the seeds are deposited carefully
initially to fix the prostate gland
by holding the stylet stationary and care-
4. The needle loading report from the pre-plan
fully withdrawing the needle over the
that indicates for each needle: (a) the x and y
stylet (done carefully as if the needle is
coordinates, (b) the number of seeds, and (c)
pulled out too swiftly, the seeds may slip
retraction of needle tip from base plane (z
inferiorly)
coordinate)
8. Good coverage of the prostate is ensured by
5. Needle types
a fluoroscopic image and ultrasound scan
• Needles—usually fixed number of 2–5
from base to apex of the prostate
seeds
9. The seed number has to be counted and
• Needles with special loadings (no seeds
accounted in the fluoroscopic images before
in the middle portion)—used adjacent to
leaving the operating room
the urethra to keep the urethral dose low
19 Prostate Brachytherapy 125

10. Survey the operating area—using Geiger– • CTV-P = CTV for prostate (on post-­
Muller counter or scintillation detector for implant imaging)
misplaced seeds • CTV-PM = CTV for prostate +0.3 cm 3-D
11. Cystoscopy—if clinical suspicion of loose uniform margin
seeds in the bladder. 2. Prostatic urethra—urinary catheter or aerated
gel helps in defining prostatic urethra
19.4.3.4  tep 4: Post-Implant
S 3. Rectum—outer and inner walls are contoured
Dosimetry on MRI and outer rectal wall if only CT
Post-implant dosimetry (CT based) must be per-
formed within 60 days of the implant (ABS)

• For palladium-103, 16 ± 4 days 19.4.4 Post-Implantation Care

• For iodine-125, 30 ± 7 days.
• Perineal bruising—conservative management
Figure 19.4 shows week 3 post-implant and perineal ice packs may be helpful
dosimetry. • Prophylactic antibiotics are recommended for
Dosimetry reporting in LDR prostate brachy- 1 week after implant
therapy is summarized in Table 19.6. • Obstructive and irritative urinary—alpha-­
ESTRO recommendations for post-implant blockers can improve urinary morbidity [3]
dosimetry evaluation [2]: • Prophylactic anti-inflammatory drugs useful
to improve dysuria
1. Two prostate CTV should be reported: • Loose seeds passing via the urethra

Fig. 19.4 Week 3 post-implant dosimetry (base to the apex)

126 P. Giridhar and A. Turaka

Table 19.6 Published recommendations from ABS [1, 3] and ESTRO/EAU/EORTC [2, 6] on post-implant dosimetry
reporting in LDR prostate brachytherapy
ABS ESTRO/EAU/EORTC
Primary parameters Secondary parameters
Mandatory May be reported
Prostate CTV D100, D90, D80 D90 V200
V200, V150, V100, V90, V80 V100 D100
V150  • Natural dose rate
 • Homogeneity index
 • Conformal index
OAR: Rectum RV100 D2cc D0.1cc
V100
OAR: Urethra UV150 D10 D0.1cc
UV5 D30
UV30 D5
Other reporting • Total volume of prostate • Volume implanted
recommendations • Number of days between implantation • Number of seeds
and post-implant imaging study • Number of needles used
• Total activity implanted
• Prescribed dose
OAR organs at risk, D90 Dose covering 90% of the prostate volume; V100 Volume that has received 100% of the pre-
scribed dose, UV urethral volume, RV rectal volume
ESTRO recommends that volume (V) parameters should always be expressed in absolute values (cc)

–– Urine needs to be passed via a sieve while 2. Position—lithotomy position, both lower
admitted in hospital limbs are abducted, externally rotated, and
–– If seeds are found in the lavatory, it can be flexed as much as possible (reduce pubic
flushed away arch interference)
• Condom use is generally recommended dur- 3. Position and fix the prostate template with
ing sexual intercourse (likelihood of ejacula- transrectal ultrasound probe onto the stepper
tion of a seed is very low) device
• Children and pregnant women should avoid 4. Cleaning and draping of the perineal area
close contact (less than 1 m) for at least one and thighs done
half-life depending on the radionuclide 5. Three-way Foley’s catheter is inserted and
used bulb inflated with 10–15 mL water (bulb
• The patient should be given written informa- must not to be pulled till bladder neck to
tion on the details of implanted sources, avoid iatrogenic puncture during needle
strength, date of implantation, and contact insertion)
numbers 6. The scrotum and penile shaft is strapped on
• Cremation not recommended for 2 years post-­ to the abdomen to avoid interference during
implantation (Risk of contamination and the procedure
release radioactive material). 7. Check transrectal ultrasound (TRUS) is
done to assess prostate volume and extent.
Further information regarding radiation safety Rectal wash with saline done if artifacts
for permanent prostate implants can be found in appear on TRUS due to minimal rectal
more detail in the ICRP 98 document [4]. content
8. Stabilization needles/fixation needles are
inserted (mid-gland peri-urethrally) to stabi-
19.5  igh Dose Rate (HDR)
H lize prostate gland
Prostate Brachytherapy 9. The next step is to image the entire prostate
gland with urethra, bladder, and anterior wall
1. Anesthesia—Combined spinal epidural of rectum at a rate of 5 mm to 1 cm/s on
anesthesia preferred TRUS. Axial images are obtained and stored
19 Prostate Brachytherapy 127

Table 19.7 Dose fractionation used in HDR brachyther- 19. Mild hematuria is common and is managed
apy (commonly used) conservatively and usually settles down
Dose per fraction Number of within 24 h post-procedure
Type of treatment (Gy) fractions 20. Once the patient is stabilized patient shifted
HDR 9.5–10.5 3–4
to recovery room.
monotherapy
HDR boost 9.5–10.5 2

19.6 Follow-up
Table 19.8 OAR constraints in HDR brachytherapy
(commonly used) 1. Follow-up at an interval of every 6–12 months
is considered suitable, digital rectal examina-
Organs at Constraint
risk parameter Value tions (DRE) and PSA at regular intervals are
Urethra V100 <90% prescription recommended
V125 <1 cc 2. Phoenix definition is recommended by ABS
V150 0 cc for defining failure (beware of PSA bounce)
Bladder V75 <1 cc (Soft 3. Prostate biopsy result may be difficult to inter-
constraint)
Rectum V75 <1 cc
pret within 30 months of brachytherapy.
V80 <0.5 cc
Consent for Images Images have been taken
from patients treated by authors as per institu-
10. The next step is target delineation on SWIFT tional guidelines and consents have been taken.
Oncentra treatment planning system
11. Organs at risk (OAR) defined include pros-
tatic urethra and rectum References
12. A pre-plan is generated and modified as
needed for the best target coverage and least 1. Davis BJ, et al. American Brachytherapy Society con-
organs at risk dose. Position of catheters sensus guidelines for transrectal ultrasound-guided
permanent prostate brachytherapy. Brachytherapy.
(HDR) that needs to be inserted on the tem- 2012;11(1):6–19.
plate are defined on the pre-plan 2. Salembier C, et al. Tumour and target volumes
13. Needle insertion done as per the pre-plan. in permanent prostate brachytherapy: a supple-
The prostate stabilization needles keep the ment to the ESTRO/EAU/EORTC recommenda-
tions on prostate brachytherapy. Radiother Oncol.
prostate stable during the procedure 2007;83(1):3–10.
14. The needles are reconstructed on images and 3. Nag S, et al. The American Brachytherapy Society
plan re-generated similar to the pre-plan with recommendations for permanent prostate brachy-
optimization as needed therapy postimplant dosimetric analysis. Int J Radiat
Oncol Biol Phys. 2000;46(1):221–30.
15. Dose fractionation is summarized in 4. International Commission on Radiological, Physics.
Table 19.7 and OAR constraints are summa- Radiation safety aspects of brachytherapy for prostate
rized in Table 19.8 cancer using permanently implanted sources. A report
16. Catheters are connected to HDR machine of ICRP Publication 98. Ann ICRP. 2005;35(3):iii–vi.
3-50
and all staff leave the OT (brachytherapy 5. Bice WS, et al. Recommendations for permanent pros-
room) and treatment is done tate brachytherapy with (131)Cs: a consensus report
17. After the dose is delivered, the catheters and from the Cesium Advisory Group. Brachytherapy.
prostate hook are removed 2008;7(4):290–6.
6. Ash D, et al. ESTRO/EAU/EORTC recom-
18. Perineum pressure is applied for 5–10 min mendations on permanent seed implantation
to decrease bleeding and minimize post-­ for localized prostate cancer. Radiother Oncol.
procedure pain 2000;57(3):315–21.
 Brachytherapy in Breast Cancer
20
Ritesh Kumar and Divya Khosla

20.1 Introduction mary tumor bed [3]. This was the rationale for
dose escalation to the tumor bed after WBI.
Radiotherapy forms an integral component in the • Randomized studies have shown that the local
management of breast cancer in both early and boost therapy reduced 5-year local recurrence
locally advanced cases. After breast-conserving rates from 7.3–13.3% to 3.6–6.3% [4, 5]. The
surgery (BCS), adjuvant external whole breast EORTC 22881-10882 trial was the landmark
irradiation (WBI) with an additional local boost study that showed significant benefit for local
is an integral part of breast conservation [1]. boost after WBI in terms of local control rates,
Brachytherapy (BT) has a role as a sole modality however, without overall survival benefit [6].
for adjuvant radiotherapy (APBI) or as a tech- 20-year follow-up of the trial showed reduc-
nique for boost [2]. In this chapter, we will focus tion in ipsilateral breast tumor recurrence
on the role of BT in breast cancer treatment and (IBTR) from 16.4% to 12% with the addition
discuss different techniques, and provide an over- of boost. The benefit was highest for patients
view of outcomes and future trends. with younger age, close margins, extensive
intraductal component (EIC), and triple nega-
tive tumors. Interstitial BT is one of the oldest
20.2 Role of Brachytherapy and widely used techniques of boost applica-
in Local Boost Therapy tion and has been used by several institutions
participating in the EORTC 22881-10882
• Adjuvant breast irradiation aims to reduce the trial.
risk of local recurrence after BCS and poten- • Photons, electrons, and intraoperative radio-
tially increase the overall survival [1]. therapy (IORT) are also other methods for
• Patterns of failure studies showed that highest delivering boost dose [7, 8].
risk of recurrence after BCS is in the peritu- • Until now, no significant difference could be
moral tissue immediately surrounding the pri- identified in terms of local control and side
effects like fibrosis between BT and other
modalities. All the modalities show excellent
R. Kumar (*) or good cosmetic outcome; however,
Department of Radiation Oncology, All India Institute prospective large randomized comparisons
­
of Medical Sciences, New Delhi, India
between the modalities are not available.
D. Khosla • The treatment volumes with BT are always
Department of Radiation Oncology, Post Graduate
Institute of Medical Education and Research, lower as compared to EBRT, thus giving BT
Chandigarh, India an advantage over external beam techniques.

© Springer Nature Singapore Pte Ltd. 2020 129

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_20
130 R. Kumar and D. Khosla

• There has been a significant reduction in radi- therapy in 27 patients, followed by the
ation dose to OAR such as lung, ribs, skin, and Ontario trial with 39 patients [11]. Both
heart with HDR BT as compared to external studies included patients with unfavorable
beam radiotherapy as seen in some studies [7]. risk factors like positive resection margins,
large tumors, and node positive disease,
resulting in high ipsilateral in-breast recur-
20.3 Role of Brachytherapy rence rates (37% and 16.2%).
in Accelerated Partial Breast • The higher rates of local recurrence in these
Irradiation trials led to further trials using strict selec-
tion criteria for APBI like young age, tumor
• Majority of the local recurrences (69–90%) size, node-negative disease, negative resec-
arises in the very close vicinity of the initial tion margins [12]. The GEC-ESTRO guide-
tumor area after BCS followed by WBI [9]. lines for APBI are summarized in
BT provides an excellent technique to give a Table 20.1.
high radiation to the tumor bed with a rapid • The development of image-based catheter
dose falloff around the target volume. implantation, implant reconstruction resulted
• The linear quadratic radiobiological model in a marked improvement in tumor dose
formed the basis of the accelerated fraction- coverage.
ation scheduling in partial breast irradiation. • The landmark GEC-ESTRO Breast Cancer
Based on the concept of radiobiological Working Group study which included 1184
equivalence, shortening a treatment course early breast cancer patients from multiple
requires decreasing the total dose, and the centers in Europe showed 5-year local con-
reduction in treated volume permits an trol, disease-free survival, and overall sur-
increase in the dose per fraction to achieve the vival were similar for MIB APBI and external
same clinical outcome as with a longer treat- WBI [13].
ment course. • The standard HDR BT dose for APBI is 34 Gy
• The techniques for APBI are summarized in in 10 fractions in 5 days (two fractions per
Fig. 20.1. day, 6 h apart).
• The initial APBI trials used BT in form of • APBI using MIB is one of the options for local
multicatheter interstitial brachytherapy treatment of ipsilateral breast tumor recur-
(MIB) where multiple interstitial catheters rence (IBTR) after a second course of BCS
delivered radiation to the lumpectomy cav- with promising results on local control [14].
ity [10]. The earliest trials using MIB for But as of now, radical mastectomy is still
APBI were started in the late 1980s by regarded as the gold standard treatment for
Guy’s Hospital using LDR MIB for mono- IBTR.

APBI

EBRT
BRACHY
INTRA OP
INTESTITIAL 3DCRT IMRT
BALOON HYBRID
Xray Electrons
MAMMOSITE AXXENT CONTURA SAVI CLEARPATH
SINGLE CATHETER XRAY SOURCE- MULTI CHANNEL PORTABLE
LUMEN SMALL THIRD 3 LUMEN
LUMEN SEROMA
DRAINAGE

Fig. 20.1 Techniques for APBI

20 Brachytherapy in Breast Cancer 131

Table 20.1 GEC ESTRO guidelines for patient selection for APBI
Good Intermediate High risk
Age (years) >50 40–50 <40
Tumor size <3 cm >3 cm
Nodal status (ALND/SLNB) N0 N2
Histology-IDC Unifocal Multifocal <2 cm Multifocal >2 cm
Multicentric
DCIS – Allowed
ILC – Allowed
LCIS Yes
LVSI/EIC/NACT Absent Present
ER/PR Any
Grade Any
Surgical margins Negative >2 mm Margin <2 mm Positive margin

20.4 Balloon-Based • Intraoperative electrons—ELIOT trial, a sin-

Brachytherapy Techniques gle dose of 21 Gy, similar local control and
survival compared to standard WBI [17]
• The various devices for balloon-based or
hybrid brachytherapy applicators are
MammoSite® (Hologic, Marlborough, MA, 20.6 Conclusion
USA), Contura® (Hologic), and Savi® (Cianna
Medical, Aliso Viejo, CA, USA) [15]. Radiotherapy plays an important role in breast-­
• The 5-year analysis of treatment efficacy, cos- conserving treatment, and EBRT is the most
metic outcome, and toxicity of MammoSite widely used modality. However, BT can deliver
breast BT from the American Society of radiation doses to the target volume in a highly
Breast Surgeons showed excellent results conformal way, thereby minimizing exposure of
comparable to other forms of APBI [16]. normal surrounding structures and OAR. The use
• MammoSite is a single-channel—dosimetric of modern imaging technologies like CT, or even
limitation to shape the radiation dose to the ultrasound and MRI, together with highly sophis-
target volume and OAR. ticated treatment planning software, has further
• MammoSite—Double lumen catheter with an improved the accuracy of individualized treat-
inflatable balloon at the distal tip. Inflated to a ment planning.
diameter 4–5 cm. May be inserted for treat-
ment at the time of surgery or up to 10 weeks
afterwards. References
• Multi-luminal hybrid BT devices like Contura
1. Hill DA, Friend S, Lomo L, Wiggins C, Barry M,
and Savi combine the advantage of
Prossnitz E, Royce M. Breast cancer survival, survival
MammoSite and MIB. These devices provide disparities, and guideline-based treatment. Breast
adequate targeting of the tumor bed and Cancer Res Treat. 2018;170(2):405–14.
reduced dose to critical structures [16]. 2. Vicini F, Baglan K, Kestin L, Chen P, Edmundson G,
Martinez A. The emerging role of brachytherapy in
the management of patients with breast cancer. Semin
Radiat Oncol. 2002;12(1):31–9.
20.5 Single Dose IORT 3. Darby S, McGale P, Correa C, Taylor C, Arriagada
R, Clarke M, Cutter D, Davies C, Ewertz M,
Godwin J, Gray R. Early Breast Cancer Trialists’
• May use Intraop photons and electrons
Collaborative Group (EBCTCG). Effect of
• Intraoperative photons (50 kV)—TARGIT radiotherapy after breast-conserving surgery on
trial, a single dose of 20 Gy as compared to 10-year recurrence and 15-year breast cancer
standard WBI death: meta-analysis of individual patient data for
132 R. Kumar and D. Khosla

10,801 women in 17 randomised trials. Lancet. 12. Marta GN, Macedo CR, de Andrade Carvalho H,
2011;378(9804):1707–16. Hanna SA, da Silva JL, Riera R. Accelerated partial
4. Romestaing P, Lehingue Y, Carrie C, Coquard R, irradiation for breast cancer: systematic review and
Montbarbon X, Ardiet JM, Mamelle N, Gerard meta-analysis of 8653 women in eight randomized
JP. Role of a 10-Gy boost in the conservative treatment trials. Radiother Oncol. 2015;114(1):42–9.
of early breast cancer: results of a randomized clinical 13. Polgár C, Ott OJ, Hildebrandt G, Kauer-Dorner
trial in Lyon, France. J Clin Oncol. 1997;15(3):963–8. D, Knauerhase H, Major T, Lyczek J, Guinot JL,
5. Polgár C, Jánváry L, Major T, Somogyi A, Takácsi-­ Dunst J, Miguelez CG, Slampa P. Late side-effects
Nagy Z, Fröhlich G, Fodor J. The role of high-­ and cosmetic results of accelerated partial breast
dose-­rate brachytherapy boost in breast-conserving irradiation with interstitial brachytherapy versus
therapy: long-term results of the Hungarian National whole-breast irradiation after breast-conserving
Institute of Oncology. Rep Pract Oncol Radiother. surgery for low-­ risk invasive and in-situ carci-
2010;15(1):1–7. noma of the female breast: 5-year results of a ran-
6. Vrieling C, van Werkhoven E, Maingon P, Poortmans domised, controlled, phase 3 trial. Lancet Oncol.
P, Weltens C, Fourquet A, Schinagl D, Oei B, 2017;18(2):259–68.
Rodenhuis CC, Horiot JC, Struikmans H. Prognostic 14. Hannoun-Levi JM, Resch A, Gal J, Kauer-Dorner
factors for local control in breast cancer after long-­ D, Strnad V, Niehoff P, Loessl K, Kovács G, Van
term follow-up in the EORTC boost vs no boost Limbergen E, Polgár C, GEC-ESTRO Breast Cancer
trial: a randomized clinical trial. JAMA Oncol. Working Group. Accelerated partial breast irradia-
2017;3(1):42–8. tion with interstitial brachytherapy as second con-
7. Kindts I, Laenen A, Depuydt T, Weltens C. Tumour bed servative treatment for ipsilateral breast tumour
boost radiotherapy for women after breast-­conserving recurrence: multicentric study of the GEC-ESTRO
surgery. Cochrane Libr. 2017;11:CD011987. Breast Cancer Working Group. Radiother Oncol.
8. Sedlmayer F, Reitsamer R, Wenz F, Sperk E, Fussl 2013;108(2):226–31.
C, Kaiser J, Ziegler I, Zehentmayr F, Deutschmann 15. Dickler A, Patel RR, Wazer D. Breast brachy-
H, Kopp P, Fastner G. Intraoperative radiotherapy therapy devices. Expert Rev Med Devices.
(IORT) as boost in breast cancer. Radiat Oncol. 2009;6(3):325–33.
2017;12(1):23. 16. Shah C, Vicini F, Shaitelman SF, Hepel J, Keisch
9. Shah C, Wobb J, Manyam B, Khan A, Vicini M, Arthur D, Khan AJ, Kuske R, Patel R, Wazer
F. Accelerated partial breast irradiation utilizing DE. The American Brachytherapy Society consensus
brachytherapy: patient selection and workflow. J statement for accelerated partial-breast irradiation.
Contemp Brachytherapy. 2016;8(1):90. Brachytherapy. 2018;17(1):154–70.
10. Sumodhee S, Strnad V, Hannoun-Lév 17. Bennion NR, Baine M, Granatowicz A, Wahl
JM. Multicatheter interstitial brachytherapy for breast AO. Accelerated partial breast radiotherapy: a review
cancer. Cancer/Radiothérapie. 2018;22(4):341–4. of the literature and future directions. Gland Surg.
11. Njeh CF, Saunders MW, Langton CM. Accelerated 2018;7(6):596–610.
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 Brachytherapy in Soft Tissue
Sarcoma 21
Prashanth Giridhar and Susovan Banerjee

21.1 Indications 21.3 Procedure of Interstitial

for Brachy-Monotherapy Brachytherapy
(Perioperative)
All three criteria must be met for monotherapy
1. Brachytherapy catheter insertion is done at
1. High grade sarcoma (FNCLCC grading) the time of surgery
2. Negative margins (>1 cm) 2. After gross tumour is resected out by sur-
3. <10 cm size geon, clips are placed in tumour bed
• FNCLCC grading of sarcoma is sum- 3. The tumour bed and areas at risk of residuum
marised in Fig. 21.1 and microscopic disease are delineated
4. The planned points of entry and exit are
marked with ink on skin close to incision site
21.2 Indications of Combined 5. Insertion of catheter started usually at per-
Brachytherapy and External pendicular direction to incision
Beam Radiotherapy 6. Insertion is done parallel to incision if
tumour bed follows curvature of extremity
1. Low grade sarcoma >5 cm size 7. Initially, a straight cutting needle is placed
2. >10 cm size inside a hollow metallic stylet and inserted
3. Positive or close margins not amenable to through points of entry and brought out
re-resection through points of exit (Fig. 21.4)
8. The cutting needle is now removed from
The doses and special considerations as stylet
defined by American Brachytherapy Society 9. The plastic catheters with button on one end
are summarised below in Figs. 21.2 and 21.3 are threaded through the hollow metallic
stylet
10. The metallic stylet is removed and button
placed in the free end
P. Giridhar (*)
11. The entry and exit point at skin is kept at
Department of Radiation Oncology, All India Institute least 1 cm from incision
of Medical Sciences, New Delhi, India 12. Catheters are placed parallel to each other
S. Banerjee and at 1–1.5 cm between each other
Medanta Medicity, New Delhi, India (Fig. 21.5)

© Springer Nature Singapore Pte Ltd. 2020 133

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_21
134 P. Giridhar and S. Banerjee

Fig. 21.1 FNCLCC grading of Tumour Differentiation

soft tissue sarcoma
Score 1 Sarcomas closely resembling normal adult mesenchymal
tissue (e.g., well differentiated liposarcoma and
leiomyosarcoma).
Score 2 Sarcomas for which histological typing is certain (e.g.,
myxoid liposarcoma & conventional leiomyosarcoma)
Score 3 Embryonal and undifferential sarcomas, Pleomorphic
sarcomas, synovial sarcomas, osteosarcomas, PNET)
Mitotic Count
Score 1 0–9 mitoses per 10 HFP*
Score 2 10–19 mitoses per 10 HFP*
Score 3 _
>20 mitoses per 10 HFP*
Tumor Necrosis, determined on histologic sections
Score 0: No tumor necrosis
Score 1: Less than or equal to 50% tumor necrosis
Score 2: More than 50% tumor necrosis
Histological grade
Grade 1 Total score 2,3
Grade 2 Total score 4,5
Grade 3 Total score 6,7,8

13. If gross residual disease is present, double 4. Sterile precautions should be taken during
plane implant may be needed removal of catheter after treatment.
14. The distance between planes should also be
1–1.5 cm
15. The wound is closed by surgeons after drain 21.5 Intra-operative
placement Radiotherapy (IORT)
16. Negative pressure wound therapy is Retroperitoneal Soft Tissue
encouraged Sarcoma (Important Points)
17. Flagging and numbering of catheters in order
is done. 1. Radiotherapy dose is delivered during surgery
2. Dose limiting structures like the bowel and
nerves are displaced from tumour bed and
21.4 Special Considerations shielded
during and after Procedure1 3. Pre-operative EBRT to a dose of 50–55 Gy in
conventional fractionation delivered
1. Avoid penetrating blood vessels during cathe- 4. Maximal resection is done 4–6 weeks after
ter insertion EBRT
2. Avoid direct contact of catheter with bone and 5. Criteria for IORT:
nerve (a) Surgery likely to be incomplete
3. The buttons should not be placed too tight (b) Absence of distant metastases
with skin (to allow expansion due to seroma (c) Displacement of dose limiting structures
formation) possible
6. IORT can be delivered with HDR brachyther-
apy, electrons or kV X-rays. The specific dif-
1
For further reading regarding procedure, readers may ferences are discussed elsewhere
review ABS guidelines by A O Naghavi et al.
 21

Recommended BT prescription dose and constraints for primary STS

BT type Modality EBRT (Gy) BT (Gy) BT duration (d) Dosing
LDR/PDR BT 45–50 4–6 0.45–0.5 Gy/h
BT + EBRT 45–50 15–25 2–4 0.45–0.5 Gy/h
HDR BT 30–50 4–7 2–4 Gy bid
BT + EBRT 45–50 12–20 2–3 2–4 Gy bid
IORT IORT + EBRT 45–50 10–20 Intraoperative 1 fraction
Volume Constraints Common Ideal
Brachytherapy in Soft Tissue Sarcoma

CTV V100 _
>90% _
>95%
V150 _
<50% _
<40%
D90 _
>90%a _
>100%a
DHI _
>0.6 _
>0.8
OAR Constraints IORT (Gy) Postoperative BT (Gy) SBRT end point (adapted OAR) Comments
Skin D0,1cc 20 40 Ulceration <
_2/3 the prescribed dose
D2cc 18 37 (Skin)
Nerve D0,1cc 16 32 Neuropathy Full dose if involved
D2cc 14 30 (Cauda equina/sacral plexus) (Max BT ~50 Gy)
Vascular D0,1cc 20 53 Aneurysm Full dose if involved
D2cc 18 47 (Great vessels
Bone D0,1cc 20 43 Fracture Caution with periosteal stripping
D1cc 18 35 (Ribs) avoid acral bone BT
Stomach/Duodenum D0,1cc 12 32 Ulceration/fistula IORT <15 Gy, avoid postoperative
D1cc 11 18 (stomach/duodenum) BT in upper abdomen
BT = brachytherapy; CTV = clinical tumor volume; DHI = dose homogeneity index; EBRT = external beam radiation therapy; HDR = high-dose rate;
LDR = low-dose rate; OAR = organ at risk; PDR = pulsed dose radiation; SBRT = stereotactic body radiation therapy.

Fig. 21.2 American Brachytherapy Society guidelines for doses in soft tissue sarcoma
135
136 P. Giridhar and S. Banerjee

Considerations when treating with brachytherapy

Specific situation Preferred treatment Treatment considerations To minimize toxicity

Extremity/trunk
Low grade: Superficial. Surgery alone Limb-sparing surgery • Nomograms available to assess risk
<5 cm, and wide (consider RT if >10% 5-y risk)
margin (_>1 cm)
High grade: <10 cm and BT alone 30–50 Gy
• Avoid acral lesions (esp. phalangeal)
negative margin • <10 catheters
• <
_ 1-cm dose depth
• <
_4.5 Gy/fraction
• <9,000 eGy to nerve
• >5 d postop
Low grade: deep, >5 cm, or BT + EBRT BT + EBRT >60 Gy • Lower extremity; TV 150 ≤ 27 mL
negative margins (<1 cm) • BT > 5 d postop
High grade: >10 cm • Chemo > 10 d after BT
negative margin
All grades: close/positive margin BT + EBRT BT + EBRT _>65 Gy • Delineation of margin required
• Re-resection if possible
Recurrent (not previously radiated) BT + EBRT BT + EBRT _>65 Gy • Flap closure
• Staged reconstruction with NPWT
Re-irradiation BT alone 30–50 Gy • Limit radiation to wound closure
• Fresh vascularized tissue closure
• Staged reconstruction with NPWT
• Cumulative dose <111 Gy
• Re-irradiation dose <60 Gy
Special considerations
Retroperitoneum BT + EBRT BT + EBRT _>60 Gy • Avoid postop BT to upper abdomen
• IORT <15 Gy
• Tissue expander
• IMRT +_ integrated boost
Head and Neck BT + EBRT IORT >15 Gy • <
_4 Gy/fraction bid (postop BT)
• <5 catheters
• TV150 <13 cc
• Mandible/vascular D10 < 4 Gy
Pediatrics BT alone Consider adding IMRT/protons • Avoid in children age <
_6 y
for extensive disease • HDR-IORT <12 Gy
• Maximal safe resection (HNC)
• Incorporate iodine-125
• Cover residual disease (vulva/vaginal)
BT = brachytherapy; EBRT = external beam radiation therapy; HDR = high-dose rate; IORT = intraoperative radiation therapy; NPWT = negative
pressure wound treatment; postop = postoperative.

Important considerations:
• Avoid acral lesions
• Keep dose < 4.5 Gy per fraction
• Brachytherapy treatment to start > 5 days after surgery
• Strongly consider wound management with negative pressure wound therapy

Fig. 21.3 American Brachytherapy Society special considerations in soft tissue sarcoma

Fig. 21.4 Catheter

implantation for
brachytherapy soft tissue
sarcoma
Incision site

Metallic needle and

stylet placed
perpendiclar to incision

Parallel needles at
1 cm distance
21 Brachytherapy in Soft Tissue Sarcoma 137

a b

Clips Clips 12
>
_2cm
>
_2cm
Clips 11

1–1.5cm 10

CTV/PTV
1–2cm 1–2cm
1–2cm 1–2cm 6
5
4
3
>
_2cm Clips >
_2cm 2
1
Clips

Fig. 21.5 Brachytherapy planning for soft tissue sarcoma shows tumour bed with clips, placement of plastic catheters
(a) and CTV (b) (courtesy: Naghavi et al.)

7. For HDR brachytherapy, HAM (Harrison

Anderson Mick) applicator is used (Fig. 21.6)
8. IORT doses:
(a) R0 resection: 10–12 Gy
(b) R1 resection (Positive margins):
12.5–15 Gy
(c) Gross residual disease: 15–20 Gy
9. The organs at risk dose limits are provided in
Fig. 21.2. Other applicator used primarily for
skin brachytherapy also being used in IORT is
the Freiburg applicator.
Fig. 21.6 HAM applicator (courtesy: Larrier et al.), cath-
eters placed at 1 cm distances, placed directly on tumour
bed after displacing OARs
 Surface Mould Brachytherapy
22
Rony Benson, Supriya Mallick, and Goura K. Rath

Mould brachytherapy includes delivery of radio- Steps

therapy by mould designed to provide a constant • Step 1—Patient selection—Only patients
and reproducible frame for source positioning. with superficial tumors with depth less than
Moulds are made to fit to the external patient 5 mm and where mould can be applied are
surface and the catheters must remain in the exact suitable candidates [2]. This is the first and
position during each radiation fraction. most important step in successful imple-
Surface mould brachytherapy can be delivered mentation of mould brachytherapy proto-
by two techniques cols. Patients with tumor depth more than
1 cm may require interstitial implants.
• Custom made implants–custom made to fit to
• Step 2—Perpetration of mould and fixing of
the external patient surface—more useful for
catheters. The catheters should be parallel
irregular surfaces [1]
to each other and at a distance of 1 cm
• Predesigned applicators like H.A.M and Freiburg.
(Fig. 22.1)
A customized mould can be made from –– In order to avoid large dose gradient over
the skin, the catheters must be placed at
• Acrylic resin
least 5 mm from skin
• Wax
–– In order to ensure proper dose delivery
• Thermoplastic material.
on borders of target, catheters must be
Indications placed to cover the whole target with
• Skin cancer margin
• Selected cases of T1-T2N0 M0 hard palate, • Step 3—Planning CT (0.5–1 cm thick cuts)
soft palate and contouring of the volumes and planning
(Fig. 22.2)
• Step 4—Plan evaluation—Coverage and
R. Benson (*) homogeneity
Department of Medical Oncology, RCC, –– D90
Thiruvananthapuram, India –– VPTV[90–150] = Volume of PTV receiv-
S. Mallick ing 90–150% of prescribed dose
Department of Radiation Oncology, National Cancer –– Conformal index (CI)
Institute-India (NCI-India), Jhajjar, Haryana, India
–– Homogeneity index (HI)
G. K. Rath • Step 5—Treatment delivery (Fig. 22.3)—
Dr. B.R. Ambedkar Institute-Rotary Cancer Hospital,
All India Institute of Medical Sciences, Ensure proper fitting of the mould during
New Delhi, India each fraction. It is very important that the

© Springer Nature Singapore Pte Ltd. 2020 139

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_22
140 R. Benson et al.

Fig. 22.1 Making a surface mould implant

Fig. 22.2 Radiotherapy planning for surface mould implant

mould is in same position as planning and • Cheap and easy to perform with available
there is no misplacement of catheters. brachytherapy machine
• With the availability of 3D-planning highly
Advantage conformal radiotherapy can be delivered.
• Mould can be used for flat surfaces and irregu-
lar shapes (e.g., earlobe or nose, a potential
advantage over electrons and also for elec- Dose Fractionation
tronic brachytherapy) • The usual dose as in other skin brachytherapy
• It is a reasonable alternative to surface elec- which delivers a dose 60 Gy LDR equivalent
tronic brachytherapy • The fraction size depends on the volume
irradiated.
22 Surface Mould Brachytherapy 141

Source of Images The image was taken from a

patient treated by authors as per hospital protocol
and consent was taken.

References
1. Kuncman L, Kozłowski S, Pietraszek A, Pietrzykowska-
Kuncman M, Danielska J, Sobotkowski J, et al. Highly
conformal CT based surface mould brachytherapy for
non-melanoma skin cancers of earlobe and nose. J
Contemp Brachytherapy. 2016;8(3):195–200.
2. Guinot JL, Rembielak A, Perez-Calatayud J,
Rodríguez-Villalba S, Skowronek J, Tagliaferri
L, et al. GEC-ESTRO ACROP recommenda-
tions in skin brachytherapy. Radiother Oncol.
2018;126(3):377–85.
Fig. 22.3 Radiotherapy plan execution for surface mould
implant
 Part III
Practical Planning Aspects and Plan
Evaluation
 Plan Evaluation in 3D Conformal
Radiotherapy 23
Subhas Pandit

The goal of radiotherapy treatment is to deliver To select plan whose dose distribution fulfills
adequate dose to tumor while limiting dose to the clinical requirement is a difficult task, as it
surrounding normal structure to reduce side-­ involves analysis of large amount of qualitative
effects. Plan evaluation is a critical decision-­ and quantitative data. Oncologists generally uti-
making step in radiotherapy planning process to lize 3D display of dose distribution, dose statis-
ensure that the treatment plan meets this goal. tics, and dose–volume histogram to answer these
two questions [1].

23.1  hat Is Radiotherapy

W 1. Is this plan good for treating a patient?
Treatment Plan? 2. Which plan is better? Plan A or Plan B?

In 3D-conformal radiotherapy, treatment plan is a Treatment plan evaluation and approval are
computer generated instruction set which key responsibilities of treating oncologist. It
includes information on beam arrangement, should be done in an orderly and systematic man-
geometry, energy, 3D image set with localization ner similar to checklist approach in surgery. Any
coordinates, and dose prescription information. error identified at this stage can be corrected
This instruction set is generated in computer sys- before actual delivery of radiation.
tem called treatment planning system (TPS).

23.3 Methods of Displaying Dose

23.2 How to Evaluate a Plan?
Before the use of computers in radiotherapy, plan-
After completion of planning and dose calcula- ning was a manual process. External contour of
tion by the physicist, radiation oncologist evalu- patient was generated using a wire and was drawn
ates the plan. Plan is selected for treatment if its in a paper. Isodose chart of individual radiation
dose distribution fulfills the medical prescription; fields was traced over the contour. Resultant dose
otherwise it again goes in iterative process of re-­ distribution was calculated, normalized and iso-
planning and re-evaluation. dose lines were drawn joining points with equal
dose. These isodose lines were usually drawn in a
single mid-transverse plane and evaluated.
S. Pandit (*)
Kathmandu Cancer Center, Kathmandu, Nepal Advances in CT simulation and computer TPS
e-mail: dr.subhas@kccrc.org in 1990s made this method of plan evaluation

© Springer Nature Singapore Pte Ltd. 2020 145

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_23
146 S. Pandit

a b

Fig. 23.1 (a) Dose distribution displayed with isodose line in transverse and coronal plane. (b) Same distribution
shown in color wash in transverse, coronal, and sagittal section

inadequate. Evaluation of 3D conformal plan condenses large amount of 3D dose distribution

required 3D visualization of radiation plan. New data into a simple 2D curve [2, 3].
methods of observing and evaluating the plans in In DVH, dose is in horizontal axis and volume
TPS monitor were developed. in vertical axis. Both dose and volume can be in
Now isodose lines could be drawn in all the relative or absolute scale. So there can be four
transverse sections, superimposed over planning possible combinations in axis which should be
CT images. Moreover, they could be drawn in noted carefully. DVH can be plotted in differen-
sagittal and coronal planes too (Fig. 23.1). tial form or cumulative form. Cumulative DVH is
Dose color wash is another tool commonly more commonly used in clinics for plan evalua-
used to visualize dose distribution. Calculated tion. Figure 23.2 shows differential and cumula-
dose in each voxel is color-coded and superim- tive dose–volume histogram.
posed over planning CT image. Color tempera- DVH has certain limitations. As there is loss of
ture is scaled to a certain dose range which can be spatial information, it cannot tell about location of
visually reviewed over grayscale image. This overdose or under dose in plan. DVH is calculated
color wash can be scrolled in transverse as well only from contoured structure. So if a structure is
as coronal and sagittal planes. By simultaneously not delineated, then its DVH cannot be analyzed.
changing display plane in transverse, coronal, If these are hotspots outside contoured volume, it
and sagittal planes, impression of dose distribu- can be missed in DVH. Figure 23.3 shows a clini-
tion in 3D is created. cal example to use a DVH.

23.4 Dose–Volume Histogram 23.5 Dose Indices

Dose–volume histogram (DVH) is a frequently These are scalar quantity which can be deduced
used tool in plan evaluation at it allows rapid from DVH. Also known as dose statistics, they
visual inspection of dose range and uniformity. provide quantitative information on dose
DVH is a graphical representation of frequency received by target or OAR and are valuable in
distribution of dose in a defined structure. DVH plan evaluation.
23 Plan Evaluation in 3D Conformal Radiotherapy 147

Fig. 23.2 Differential

Differential Cumulative
and cumulative dose–
volume histogram. V V
CTV
Source: David S. Chang. o o
(2014). Basic l l CTV
Radiotherapy Physics Cord
u u
and Biology. Springer
m m
Cord
e e

Dose 100% Dose 100%

Fig. 23.3 DVH of Target and OAR. Ideally target DVH should be flat up to 100% dose and a sharp falloff thereafter.
For OAR, DVH should fall to 0% dose as early as possible

Some commonly used physical dose indices are: Some radiobiologically based indices in use
are:
• Minimum dose to the volume
• Maximum dose to the volume • Tumor control probability (TCP)
• Mean dose to the volume. • Normal tissue complication probability
(NTCP)
When reporting these indices, point dose can • Probability of uncomplicated tumor control (P+)
be spurious. So minimum volume of • Equivalent uniform dose (EUD)
3 mm × 3 mm × 3 mm (= 0.03 cc) is usually
defined as a point.
Dose–Volume Parameters: 23.6 Steps of Plan Evaluation
• Vd: Volume of structure that receives more 23.6.1 Field Arrangement
than or equal to dose D
• Dv: Dose that a volume V of a structure First step in plan evaluation is to look for beam
reaches or exceeds selection. In 3D conformal radiotherapy planning
physicist chooses the beam angle and aperture.
Both V and D can be absolute or relative, so Responsibility of oncologist is to look at each
they need to be interpreted according to their use. field and see that arrangement is sensible. Beam
For example, V20 in lung means 20Gy dose. angles are more important when number of
148 S. Pandit

beams is limited. Beam entry and exit should 23.6.2 Dose to Target
generally avoid critical normal structures. There
should not be excessive normal tissue in beam Next step in plan evaluation is to look for coverage
path. For example in brain tumors, vertex field is and homogeneity of dose within target. Target cov-
commonly used (Fig. 23.4). It should be ensured erage can be deduced from cumulative
that they are not exiting to neck/chest. Non-­ DVH. Planner can aim for different PTV coverage
coplanar beam has relatively complex beam path based on specific protocol or departments practice.
and needs careful overview. Common PTV coverage prescriptions in use are
Beam can be evaluated in both room-eye-view
(REV) to look for field arrangement and individ- • 95% of prescription dose to cover 95% of
ual beam’s eye view (BEV) to look for MCL PTV (95/95)
shaping and relation to OARs [4]. Numbers of • 100% of prescription dose to cover 95% of
field and beam geometry are important in scoring PTV (100/95).
plan. For example, non-coplanar and multi-field
plan are more time consuming to deliver. So they It is advisable not to cover 100% PTV with pre-
are generally avoided in palliative plans. scription dose as forcing dose to cover all of PTV
can create unacceptable hot regions. Plan should
be normalized such that at least 95% of PTV is
covered by prescription dose. It ensures that no
part of PTV is under-dosed by more than 5%.
According to ICRU 50, entire PTV should be
covered by 95–107% of prescription dose.
Then DVH of all targets including CTVs and
GTV is analyzed. DVH of multiple plans can be
displayed in single graph for rapid comparison.
As DVH does not give spatial information, it
should always be analyzed together with 3D dose
distribution. A clinical example to use DVH to
compare two plans is shown in Fig. 23.5.
Next step is qualitative evaluation by visual
Fig. 23.4 Anterior-lateral beam arrangement with wedge inspection of 3D dose distribution. Isodose con-
pair in a case of brain tumor tour and color wash superimposed over structure

Fig. 23.5 Comparison 100

of two plans using DVH
of both loaded in a same
graph 80
Volume (%)

60

40

20

0
0 20 40 60 80 100 120
Dose (%)
23 Plan Evaluation in 3D Conformal Radiotherapy 149

contour in CT images are used. Prescription iso- 23.6.3 Dose to Organs at Risk [5–7]
dose should cover the PTV. Color wash is usually
set from 95% to 107% of dose and visual inspec- Individual organs at risk are assessed in dose
tion of each transverse section is done. Inadequate distribution as well as DVH and dose statistics.
coverage, dose inhomogeneity, and excessive Good practice is to look for one OAR at a time.
spills outside PTV can be identified. Color wash Some OAR like optic structure, spinal cord is
can be independently windowed to look for spe- more critical than others like parotids or oral
cific feature in plan. For example, it can be set in cavity. Guidelines like QUANTEC are helpful
higher dose level to see for distribution of hotspot. to ensure that OAR dosages are within the lim-
Likewise, lower dose level is set to look for spills. its. It should be ensured that there are no
While evaluating hot and cold spots, volume, hotspots in OAR.
magnitude, and location are to be assessed.
Serial Organs Maximum dose is crucial. In
• By definition, cold spot is inside PTV while some crucial organs like spinal cord, toxicity
hotspot may be inside or outside PTV, can be devastating in form of radiation myeli-
• Cold spot should be <1% of PTV, preferably tis. Therefore, conventional 5/5 (5% probabil-
located in periphery of PTV and not inside ity of complication in 5 years) is unacceptable.
CTV, So, stringent limit like 0.2% probability with
• Hotspot should be less than 15–20% of PTV conventional dose of 50 Gy is selected as dose
and <15% above prescription dose. Hotspots limit.
should be inside CTV and preferably inside
GTV. Parallel Organs Mean dose and dose–volume
parameter are more important. For example in
Figure 23.6 shows plan evaluation displaying lung cancer, volume of lung receiving 20 Gy or
color wash in transverse. more (V20) corresponds with radiation pneumo-
nitis and is limited below 35%. Similarly to
reduce xerostomia, mean dose of parotid gland is
limited to <26 Gy.

23.6.4 Dose to Remaining Volume

In radiotherapy practice, only tumor target and

critical normal structures are contoured. Critical
structures are those whose tolerance can alter
radiotherapy plan. So much of irradiated volume
is not contoured hence not seen in DVH. However,
it is good practice to evaluate dose in these
“remaining volume at risk” (RVR) to avoid
unwanted dose deposition.
Important points:

• Always evaluate plan in absolute dose.

• DVH is helpful for plan evaluation. But should
not be relied solely to approve plan.
Fig. 23.6 Plan evaluation displaying color wash in
transverse, coronal, and sagittal sections along with DVH • DVH should always be evaluated with dose-­
and BEV window display and dose statistics.
150 S. Pandit

• Simple plan scores over complex plan. For Pediatrics

similar dose distribution, plans having fewer • Treatment may require general anesthesia.
and simpler beam arrangement are chosen Shorter treatment time is preferred.
over complex plan. This is especially true in • Whole of vertebra should be irradiated if some
palliative cases. part comes in treatment field, to avoid growth
deformity.
Head and Neck • Dose to gonads should be considered and
• Beam should not enter directly through eye. minimized.
• There should not be direct vertex beam exiting
into body. Source of Images The image was taken from a
• If possible, avoid bilateral beams for the patient treated by authors as per hospital protocol
tumors located away from midline. and consent was taken.
• If possible, avoid beams entering through
shoulder region while treating tumors extend-
ing inferiorly. References
• OAR should not get more than 105% of pre-
scribed dose (spine, brainstem). 1. Drzymala RE, Holman MD, Yan D, et al. Integrated
software tools for the evaluation of radiotherapy
treatment plans. Int J Radiat Oncol Biol Phys.
Thorax 1994;30(4):909–19.
• Evaluate V20 in lung cases. Low dose spills 2. Drzymala RE, Mohan R, Brewster L, et al. Dose–
are important in lung. volume histograms. Int J Radiat Oncol Biol Phys.
• Try to avoid contralateral lung from field. 1991;21(1):71–7.
3. Mohan R, Barest G, Brewster IJ, et al. A comprehen-
• There should be adequate skin flash (2 cm) in sive three-dimensional radiation treatment planning
breast cases. system. Int J Radiat Oncol Biol Phys. 1988;15:481–95.
• To reduce lung dose mean lung distance of 4. Purdy JA, Harms WB, Matthews JW, et al. Advances
beam should be minimum (<2.5 cm). in 3-dimensional radiation treatment planning sys-
tems: room-view display with real time interactivity.
• If SCF is present in breast case, there Int J Radiat Oncol Biol Phys. 1993;27(4):933–44.
should not be any overlap or gap between 5. Milano MT, Constine LS, Okunieff P. Normal tissue
the fields. tolerance dose metric for radiation therapy of major
organs. Semin Radiat Oncol. 2007;17(2):131.
6. Marks LB, Ten Haken RK, Martel MK. Guest Editor’s
Pelvis introduction to QUANTEC: a users guide. Int J Radiat
• More than 105% of prescribed dose should Oncol Biol Phys. 2010;76(Suppl):S1–2.
not be in bowel region. 7. Bentzen SM, Constine LS, Deasy JO, et al.
• Femoral heads should be shielded without Quantitative Analyses of Normal Tissue Effects in
the Clinic (QUANTEC): an introduction to the scien-
compromising PTV. tific issues. Int J Radiat Oncol Biol Phys. 2010;76(3
• High energy beam (10–15 MV) is preferred. Suppl):S3–9.
 Plan Evaluation in IMRT and VMAT
24
Sandeep Muzumder and M. G. John Sebastian

24.1 Introduction for many tumors, especially in head and neck

cancer (HNC). Though IMRT has revolutionized
Radiation therapy for treatment of malignant the way of EBRT delivery, it is prudent to realize
disease results in damage of both tumor and nor- that IMRT process does not guarantee an opti-
mal cells. Better therapeutic ratio is achieved mal solution in all cases. ICRU report 83 gives a
with increasing dose to target with lesser dose to detailed introduction to IMRT and new reporting
organ at risk (OAR). Radiation therapy has guidelines [1]. The numerous ways of imple-
evolved over time from manual planning to con- menting IMRT are enumerated in Table 24.1. All
formal therapy. The multi-leaf collimators have
replaced the use of wedges and compensators, Table 24.1 Types of IMRT
and hence simplified radiation delivery by better Static gantry Gantry delivering from a small
conforming the tumors. The improved imaging, number of fixed angles
especially (computed tomography) CT scan, and  Segmental MLC static during beam delivery
MLC
better treatment planning system have paved (step-and-­
way for intensity-modulated radiation therapy shoot)
(IMRT). IMRT is a form of 3DCRT where TPS  Dynamic MLC MLC moves at different rates
determines non-uniform fluence to attain cus- (sliding during beam delivery
tomized dose distribution, where dose is sculpted window)
Dynamic gantry Gantry moves in one or more
to target while sparing proximal OARs. IMRT is rotating arcs during beam
carried out by delivery of multiple beamlets of delivery
non-­uniform fluence. The calculation of fluence  Cone-beam Leaves move while the gantry is
is done by high performance computers using (IMAT/VMAT) rotating
algorithms taking an iterative approach, called  Fan-beam Binary leaves modulate a fan
(tomotherapy) beam
inverse planning. The inverse planning starts
   Serial Gantry rotates around the patient
with desired result and works backwards to tomotherapy with the couch fixed. The couch
achieve best possible beam shape and fluence moves in a stepwise fashion after
pattern. IMRT has become the de facto external each rotation
beam radiation therapy (EBRT) delivery method    Helical Gantry and couch move
tomotherapy synchronously
Robotic Multiple non-coplanar pencil
radiotherapy beams delivered by a LINAC
S. Muzumder (*) · M. G. John Sebastian (*) mounted on a robotic arm
Department of Radiation Oncology, St. John’s
Medical College and Hospital, Bengaluru, India

© Springer Nature Singapore Pte Ltd. 2020 151

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_24
152 S. Muzumder and M. G. John Sebastian

implementation strategies differ in terms of low-volume providers of IMRT for HNC. The
delivery mechanism of non-uniform fluence. key finding of this population-­based study was
The LINAC and MLC based system are more the impact of experience of IMRT provider. For
versatile and acceptable. IMRT can be delivered every additional 5 patients per year, the risk of
with rotational therapy using intensity modu- mortality decreased by 21% [3].
lated arc therapy (IMAT) or tomotherapy. The
combination of dynamic MLC and arc therapy in
LINAC is called IMAT. The volumetric modu- 24.2 Plan Evaluation
lated arc therapy (VMAT) is synonymous with
IMAT. In VMAT, in addition to IMAT, there is a Evaluating a radiation plan is an essential task for
simultaneous change in dose rate, gantry speed, the radiation oncologist (RO), which has become
and collimator system. Different vendors have more complex due to IMRT. Multiple factors must
given specific proprietary names like RapidArc be evaluated before approval of final IMRT plan.
(Varian), VMAT (Elekta), and SmartArc Various checklists are available for evaluating a
(Philips), adding to the confusion of nomencla- radiation plan like SPIDERplan [4] and CB-CHOP
ture. As there is no direct comparison in clinical (https://appliedradiationoncology.com/articles/cb-
setting, the superiority of one technique over chop-a-simple-acronym-for-evaluating-a-radia-
another cannot be ascertained. tion-treatment-plan). This chapter describes the
The advantage of IMRT lies in superior con- practical approach to IMRT treatment planning
formality compared with 3DCRT. It can pro- and evaluation from a radiation oncologist’s
duce concave-shaped dose distribution, perspective.
especially useful in sparing spinal cord in HNC
which is not possible in 3DCRT without com-
promising target. Multiple simultaneous therapy 24.2.1 Patient Selection
can be delivered at the same time to same region,
in particular simultaneous integrated boost The radiation oncology department at our hospi-
(SIB). SIB may offer added radiobiologic tal decides the suitability for IMRT on evidence-­
advantage. With sharp dose fall-off at PTV based literature and dosimetric superiority over
edges, IMRT achieves excellent normal organ IMRT. This mostly includes cancer of head and
sparing. With all these advantages, various risks neck, prostate, cervix with para-aortic node, and
and uncertainties are associated with IMRT, like post-operative irradiation in stomach and pan-
the uncertainty of target delineation and dose creas. For other patients for whom IMRT may
calculations. Whether patient actually receives be beneficial, it is discussed on a case-by-case
the planned dose distribution is questionable. basis.
The geographical misses due to steep dose fall-
off at PTV margins, data remains scarce. What
is the significance of large volumes receiving 24.2.2 Patient Immobilization/
less doses, remains unknown? The fate of nor- Positioning and Simulation
mal tissues in high risk PTV receiving higher
doses in SIB? Only longer follow-­up will answer An accurate and precise patient positioning is
these questions. Also, a learning curve exists in more important, as IMRT is less forgiving com-
IMRT practice for HNC, and experience of pared with 3DCRT due to sharp dose fall-off.
treating oncologist reduces the chance of fail- Custom-made thermoplastic cast is made for
ure. The RTOG 0022 study reported higher fail- head-and-neck cancer. Vacuum bag or position-
ure in oropharyngeal cancer patients with major ing devices are used for abdominal or pelvic
IMRT protocol violations [2]. High-­volume pro- IMRT. A point to remember is that reproducibil-
viders have decreased all-cause mortality, aspi- ity may not be achieved by using immobilization
ration pneumonia, and better OS compared with devices. In a study at our institute, no-immobili-
24 Plan Evaluation in IMRT and VMAT 153

zation technique with leg separator was the most i.e., target volume and OARs, should be named
reproducible technique with the smallest PTV the remaining volume at risk (RVR). To avoid
margins in pelvic irradiation compared with high doses to unsuspected areas, RVR should
whole body vacuum bag cushion and six point receive a dose constraint. Before plan evaluation,
Aquaplast pelvic cast [5]. A radiation therapy the radiation oncologist should recheck the con-
planning (RTP) CT scan is done through the tours of target and organ at risk (OAR) once
region of interest at 2.5 mm thickness for IMRT again before starting the actual evaluation pro-
planning. cess. It is more important when contouring is
done by others. An OAR may have been omitted
unintentionally and may have to be contoured, as
24.2.3 Contouring dose spills in that OAR or it is in path of a non-­
coplanar beam.
The contouring is the most important aspect of
IMRT planning and evaluation process. An
appropriate window level and window width 24.2.4 Objectives: Target Dose
must be selected for specified contouring. A GTV and OAR Dose Constraints
might have to be contoured in two different win-
dow settings, like a chest wall-based lung lesion. The objectives must be assigned to the planning
In this case, GTV must be contoured both in lung physicist before starting IMRT plan in TPS. The
and soft-tissue window setting. Special care must common language used for these are the “D and
be taken during fusion. Many a times, the fused V” notations. These notations designate doses
MRI or PET-CT is done at different positions and volumes of target and OARs. D designates
compared with planning RT scan. A RO must the minimum absorbed dose received by percent-
remember that planning and dose distribution is age volume of the target or OARs. For example,
done on RT planning scan. MRI or PET may 99% of PTV volume will receive at least 70 Gy
show tumor better, but CT scan has better spatial and will be represented as: D99 PTV = 70 Gy.
resolution. Also, the planning process and evalu- Likewise, V designates the volume that receives a
ation is done on RTP CT scan. Hence, the prin- specified dose. For example, 20% of lung receiv-
ciple to be used is “MRI/PET finds it and RTP CT ing 30 Gy will be written as: V20 lung = 30 Gy.
scan defines it.” The contours should not be jag- These V and D notations are not to be confused
ged especially target. The skin contours should during prescription or evaluation. The next step is
be smoothed in the area of IMRT planning. Also, to identify the priority of these constraints. Here,
checking for unintended/accidental contour and RO should take a pragmatic approach and know
auto-contour should be carried out by the treating the limitation of IMRT based on experience or
RO. Any expansion of margins for CTV or PTV literature. For simplicity and better understand-
should be reviewed for accuracy. For example, a ing, the author recommends either priority 1 or
GTV or CTV may have been modified without priority 2 for the OARs. The dose received by
appropriate re-expansion of the corresponding priority 1 OARs like spinal cord and brainstem is
PTV. ICRU Report 83 strongly recommends that more important than target coverage. Whereas,
the margins not be compromised when delineat- coverage of target becomes more important than
ing the PTV or PRV, even in those situations in priority 2 OARs like salivary gland and pharyn-
which these volumes might encroach on an OAR geal constrictors. The dose trade-off among
or CTV because systematic uncertainties have multiple OARs must be communicated directly
more impact on the accuracy of absorbed dose with the planning physicist to achieve the objec-
delivered to the patient than do random uncer- tives. The Quantitative Analyses of Normal
tainties. A PTV may have to be trimmed under Tissue Effects in the Clinic (QUANTEC) dose
skin, for plan evaluation unless skin is involved constraints are most commonly used for IMRT
by tumor. Tissues outside the delineated volume, planning [6].
154 S. Muzumder and M. G. John Sebastian

24.2.5 Beam Arrangements (Gy) and Y-axis displays relative (%) or absolute
(in cc) volume of target or OARs. Often coverage
The IMRT planning process is relatively insensitive is considered adequate when at least 95% of the
to beam direction, unlike 3DCRT. But, conformality PTV is treated to the prescription dose or 95% of
increases with increase in number of beams. For prescription dose covers more than 99% of target.
IMRT plans, one should specify the number of fields Though variations are acceptable depending on
or arcs and points of entry. A typical IMRT in HNC the treating RO on a case-by-case basis, the treat-
has seven to nine fields in equally spaced angles. Two ing RO may compromise between PTV coverage
fields are never opposed in fixed-field IMRT plan. and OAR constraints to avoid unacceptable tox-
When placing non-coplanar field to enhance confor- icity. The DVH must be used with caution. As
mality, the OARs in the path must be accounted for. spatial information is lost, DVH is only a second-
The numbers of fields might be increased, if desired ary check. The appropriateness of target and
target coverage or OAR constraints are not achieved. OAR coverage cannot be assessed by DVH. The
Increasing number of fields or arcs will increase the DVH could report 100% coverage of the PTV by
treatment time. With longer treatment time, organ the prescription dose, but the PTV could be delin-
motion and patient immobilization especially in pal- eated incorrectly. There may be an excessive
liative setting becomes an issue. dose spillage in OARs, which can be seen only in
graphical dose distribution and not through a
DVH.
24.2.6 Q
 ualitative Assay: Spatial
Dose Distribution
24.2.8 Quantitative Assay:
The result of treatment plan is a prediction of dis- Heterogeneity Versus
tribution of dose deposited within patient seen on Homogeneity
RTP CT scan. The various methods of dose dis-
play are: isodose lines, color wash, isodose sur- In principle, IMRT can deliver more homogenous
face dose or isodose, and color wash combinations. plan, compared with 3DCRT due to non-uniform
The plan should be evaluated slice by slice view- fluence. Ironically, heterogeneity is the rule in
ing structure and isodose. The prescription iso- practice due to the tight constraints of proximal
dose should cover its corresponding target. Any OARs. Heterogeneity refers to the variability in
inadequate coverage or excessive dose spillage dose distribution throughout target. It includes
outside the PTV should be identified. Any examining the minimum PTV dose (cold spot)
unmarked OARs in area of dose spillage must be and the maximum body dose (hot spots), whether
contoured. The display of dose distribution on it is inside or outside PTV. In IMRT plan, accept-
RTP CT scan slice by slice is relation to target able cold spot is 95% and hotspot is 110% of pre-
and OARs is the most direct and informative scribed dose. This approach is more pragmatic in
method of assessing a plan. All other methods of present volumetric IMRT planning compared
assessing dose distribution, namely quantitative with point based 3DCRT planning. After deter-
assay, are surrogate to this and involve a loss of mining the quantitative values of the cold and hot
information to some extent. spots, it is critical to review their locations within
the treatment plan. Ideally, the hotspot should be
inside PTV, and limiting hotspots near OARs
24.2.7 Q
 uantitative Assay: Dose-­ during IMRT planning. A hot spot within the
Volume Histogram GTV may be more acceptable, as opposed to it
being in a critical OAR. Similarly, a cold spot at
Dose distribution is graphically displayed using a the edges of the PTV is preferred to it being
dose-volume histogram (DVH). In DVH, the within the GTV. Presently, the ICRU report 83 on
X-axis displays dose in relative (%) or absolute IMRT recommends evaluating and record D2 and
24 Plan Evaluation in IMRT and VMAT 155

D98. Among multiple IMRT plans, a more fraction, and fractionation schedule. The pre-
homogenous one should be approved, provided scribed dose might have to reduce if dose con-
acceptable target coverage and OAR dose con- straint to priority 1 structure is not achieved. For
straints are achieved. Homogeneity or heteroge- example, to prescription dose to target by few
neity index can be calculated, to compare grays to achieve optic chiasm dose constraints.
competing IMRT plans. Also, the beam energy, number, and angle of
beam should be noted. The image guidance pro-
tocol should be specified for each IMRT plan. It
24.2.9 O
 ARs Dose Constraints is based on the site of irradiation, PTV margin,
Evaluation and set-up error. In general, daily cone-­beam
CT is required in IMRT of carcinoma prostate,
After evaluating target coverage, next objective where daily organ motion is substantial due to
is to verify dose received by OARs. First to rectal filling. In HNC IMRT, where custom-­
check the objective assigned to planning physi- made Aquaplast cast give rise to minimal set-up
cist and identifying the priorities. Certain OARs, error, weekly imaging is adequate. But, PTV
especially serial organs have critical dose thresh- margin of less than 3 mm may necessitate daily
old beyond which unacceptable toxicity may CBCT even in HNC IMRT.
occur. These OARs are given priority 1 and their
dose constraints cannot be violated. Sometimes,
under-dosing the PTV and reducing the prescrip- 24.3 Conclusion
tion dose are the only option to achieve dose
constraints to priority 1 OARs. For example, This chapter provides a stepwise pragmatic
dose constraint of optic chiasm is more impor- approach for evaluating an IMRT plan. Since
tant to prevent blindness than target coverage. IMRT plan approval is a critical step, a checklist
Dose constraints to priority 2 OARs are less should be formulated in every department doing
important than target coverage. For example, a IMRT to reduce errors. A systematic approach
dose constraint to parotid is less important to will give rise to a common language for various
prevent xerostomia than target coverage. Both, ROs, physicists and residents for consistency and
spatial dose distribution and DVH should be easy implementation of IMRT in clinics. The
reviewed for OAR dose evaluation. In situation contouring and plan evaluation should be verified
of PTV and OAR overlap, priority of OAR by a second RO. All IMRT cases should be dis-
should be considered. Sometimes, PTV may be cussed in clinical chart review. If required, a RO
under covered or cropped to protect OARs but should never hesitate to replan for better cover-
ensuring adequate GTV coverage. The dose con- age and organ sparing. But RO should know the
straints of OARs can be found in literature. The limitations of IMRT and should not delay start of
most commonly used dose constraints are from treatment unnecessarily. Since the responsibility
QUANTEC, RTOG protocol, or recent random- for final approval of plan lies with the radiation
ized controlled trials. When dose per fraction is oncologist, it is important to have an objective
changed, it is important to change appropriate approach of IMRT evaluation. The success of
value with biologically effective dose (BED) for IMRT largely depends on imaging. ICRU report
OAR constraints. 83 states IMRT increase the need for accurate tar-
get delineation. This largely depends on training
and experience. The follow-up of patient receiv-
24.2.10 Prescription ing IMRT is required to document failure and
toxicity pattern. Correlating with patient data
The final step is to confirm dose prescription, will bring about further refinement of IMRT
i.e., to verify total prescribed dose, dose per process.
156 S. Muzumder and M. G. John Sebastian

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Clin Oncol. 2016;34:684–90.
4. Ventura T, Lopes M, Ferreira B, et al. SPIDER
1. ICRU Report 83. Prescribing, recording, and report-
plan: a tool to support decision-making in radiation
ing photon-beam intensity-modulated radiation ther-
therapy treatment plan assessment. Rep Pract Oncol
apy (IMRT). J ICRU. 2010;10(1):1–106.
Radiother. 2016;21:508–16.
2. Eisbruch A, Harris J, Garden AS, Chao CK, Straube
5. Udayashankar AH, Noorjahan S, Srikantia N, Babu
W, Harari PM, et al. Multi-institutional trial of accel-
KR, Muzumder S. Immobilization versus no immo-
erated hypofractionated intensity-modulated radiation
bilization for pelvic external beam radiotherapy. Rep
therapy for early-stage oropharyngeal cancer (RTOG
Pract Oncol Radiother. 2018;23(4):233–41.
00-22). Int J Radiat Oncol Biol Phys. 2010;76:1333–8.
6. Bentzen SM, et al. Quantitative analyses of normal
3. Boero IJ, Paravati AJ, Xu B, Cohen EE, Mell LK, Le
tissue effects in the clinic. Int J Radiat Oncol Biol
QT, et al. Importance of radiation oncologist expe-
Phys. 2010;76(3):S1–160.
rience among patients with head-and-neck cancer
 Plan Evaluation for TomoTherapy
25
Shikha Goyal and Susovan Banerjee

25.1 Introduction The treatment is essentially MV image guided

IMRT with volume-based planning and non-­
Tomotherapy is a term used for the teletherapy isocentric helical delivery. The largest field size
equipment as well as for a specific technique of that can be opened is 5 cm × 40 cm, and the small-
intensity modulated radiation therapy (IMRT) est 1 cm × 0.625 cm while owing to the helical
planning and delivery whereby the relative rela- nature of delivery, a continuous translational
tionships between the gantry, multileaf collimator length of 135 cm can be treated without interrup-
(MLC), and couch are more dynamic than in a tion. Interruptions, however, are possible to enable
conventional linear accelerator (LINAC). It has a imaging for verification at any level during the
rotating CT-gantry-like platform and a non-sta- entire length of treatment. The dose distribution
tionary couch that continually moves translation- within the target volumes is characteristically
ally inwards through the bore; the system uses a homogenous compared to other IMRT systems,
narrow pencil beam (6 megavolts, MV) for treat- although owing to the rotational/helical nature of
ment delivery in a helical manner over 360° around treatment delivery, the low dose spread is consid-
the couch enabling slice-by-slice treatment deliv- erably higher and needs particular attention.
ery. This arrangement introduces some unique
possibilities as well as limitations into the system.
It was one of the first devices with the capability of 25.2 Ideal Candidates
in-built image guidance system and uses the same for Tomotherapy
LINAC head for MV imaging for verification.
Since its first conceptualization in the early 1990s Tomotherapy is capable of treating almost all
by Mackie and Reckwerdt at University of sites and all tumors that need teletherapy with
Wisconsin, Madison to its most modern form, the photons. Owing to the characteristic of 135 cm
Radixact system by Accuray, there have been sev- length treatment capability, the system finds its
eral hardware, design and software improvements, largest application in long field junction less
making the system more robust, with clinical treatments such as whole spine or craniospinal
patient treatments ongoing since 1994 [1–3]. irradiation, total body or total marrow irradiation,
long paraaortic chain, and pelvic fields such as
extended field radiation for cervical carcinoma. It
S. Goyal (*) · S. Banerjee
Division of Radiation Oncology, Medanta Cancer
is more efficient than conventional LINACs in
Institute, Medanta the Medicity, treating complex volumes such as carcinoma anal
Gurugram, Haryana, India canal with large pelvic and inguinal nodes, whole

© Springer Nature Singapore Pte Ltd. 2020 157

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_25
158 S. Goyal and S. Banerjee

brain radiotherapy with simultaneous boost to for breast cancer. This module is called
gross metastases, whole scalp radiotherapy with TomoDirect or Topotherapy and uses a pair of
brain sparing, stereotactic body radiation therapy, opposed beams (or many sets of pairs with dif-
and stereotactic radiosurgery, etc., with better fering angulation) [8]. Unlike parallel-opposed
sparing of intervening normal tissues, and poten- beams in conventional or three dimensional
tially lesser acute toxicity [4–7]. Figures 25.1 and conformal radiotherapy, these beams are modu-
25.2 illustrate some common applications of lated across their path and are again delivered
Tomotherapy. in a slice-by-slice fashion (the gantry beam
A specific module for delivering paired field position remains fixed while the couch trans-
IMRT was developed keeping in mind the lates horizontally towards the bore). This can
requirement of tangential beam arrangement also be used to deliver parallel-opposed beam

a b

d e

Fig. 25.1 Plan images showing the various special appli- tions was planned for prostate and 45 Gy in 25 fractions to
cations of tomotherapy. (a) Adult medulloblastoma pelvic and paraaortic nodal chain as well as D10 vertebral
planned for craniospinal radiation (36 gray, Gy in 20 frac- body in a single plan. (d) Adnexal carcinoma scalp,
tions). Dose profiles are displayed in sagittal and various postop. Involved area of scalp with margin was treated to
axial sections. The outermost blue isofill represents 10 Gy. a dose of 60 Gy and bilateral neck node levels II–IV
(b) Relapsed acute leukemia planned for total body irra- treated to 54 Gy, both over 30 fractions. Cranial sparing
diation (12 Gy in 6 fractions, twice daily) as conditioning could be achieved despite the complex volume. The inner-
regime prior to stem cell transplant. The lungs received a most blue isofill represents 25 Gy. Mean cochlear dose
mean dose of 8 Gy. The blue isofill represents 3 Gy. (c) A was 21 Gy. (e) Carcinoma breast with multiple brain
case of carcinoma prostate with pelvic and paraaortic metastases. Whole brain RT of 30 Gy and simultaneous
nodes and oligometastatic disease involving D10 vertebra boost to gross metastases of 45 Gy over 15 fractions each
was planned for radiation following excellent response to was planned. A mean eye dose of 12 Gy and lens dose of
androgen deprivation therapy. A dose of 66 Gy in 33 frac- 3 Gy was achieved
25 Plan Evaluation for TomoTherapy 159

Fig. 25.2 (a) Right sided carcinoma breast T2N1M0, breast. (b) Bilateral breast cancer (right T1N0M0, left
post breast conservation surgery (BCS), planned for TisN0M0, post BCS, planned for bilateral breast irradi-
breast and supraclavicular radiation (50 Gy) and simul- ation 50.4 Gy in 28 fractions. Note the dose homogene-
taneous boost (60 Gy) in 25 fractions. Note the 10 Gy ity within target in both plans. Both cases were planned
dose splash into ipsilateral lung, liver and contralateral with helical tomotherapy

arrangements as required for palliative treat- agement in Tomotherapy, hence it is less efficient
ments, limb sarcomas, etc. This reduces the than gating or deep inspiration breath hold in nor-
overall integral dose since the beam is open for mal tissue sparing in tumors located in lower tho-
only a part of the gantry rotation, and also con- rax or upper abdomen. The system is not equipped
siderably reduces the treatment time compared for delivering simple 3DCRT treatments. Since
to helical delivery. there are no cones and the smallest field size is
still considerable, very small volume treatments
such as radiosurgery for trigeminal neuralgia or
25.3 Non-Ideal Conditions for very tiny lesions may not be deliverable with-
out significant spread-out dose.
Patients with small superficial tumors that need Some salient points about the machine that
irradiation to <1 cm depth, peripherally located influence the planning process [9, 10]:
lesions such as lateral abdominal wall mass in a
large diameter patient, any tumor needing focal 1. The LINAC energy is fixed at 6 MV without
electron therapy or total skin electron therapy, or flattening filter, irrespective of depth.
concerns with large integral doses or low dose 2. Mode of treatment delivery is helical with
spillage are not suitable for Tomotherapy. 360° gantry rotation with delivery at 51 beam
Additionally, there is no integrated motion man- angles 7° apart from each other, which means
160 S. Goyal and S. Banerjee

that the couch with be in the beam path for a 85 cm, and only accessories that would fit into
considerable period of treatment delivery and that dimension should be used. The positioning
hence attenuation due to the same has to be and immobilization devices should give a stable
accounted for in the planning process. and reproducible set up due to inability to cor-
3. Image guidance is integrated in the form of a rect rotational shifts in pitch or yaw. Indexed
fan beam MVCT beam (called CTrue) with positioning devices, whenever feasible, would
3 MV energy. No treatment fraction can be initi- minimize the possibility of rotational errors con-
ated before imaging. Imaging is 3-­dimensional, siderably. Use of bolus, or any additional devices
in treatment position and using treatment whose positioning cannot be guaranteed on a
source. The image quality may be less than for daily basis, should be limited. The side-to-­side
kilovoltage CT (KVCT) but suffices for most dimensions of the entire set up should be limited
treatments. High atomic number materials such to 70 cm or less. The target needs to be as close
as dental implants, hip prosthesis, etc., can be to the center of the bore (center of the 85 cm
imaged without artifacts unlike KVCT. ring) as feasible to ensure homogenous dose
4. The gantry bore is 85 cm and source to axis without thread effect. For this purpose, the
distance (SAD) is also 85 cm. mould room process may require off-center
5. There is one set of independent jaws (15 cm positioning of a carcinoma breast case where the
thickness) and the jaw width for various treat- target (breast) is relatively lateralized and periph-
ments can be 1 cm, 2.5 cm, or 5 cm (smaller eral. Patient is simulated in the treatment deliv-
widths for more complex or smaller field treat- ery position. Simulation should ensure that in
ments such as stereotactic body radiation therapy the region of the target, the entire circumference
(SBRT). The jaws can be in static mode or of the body as well as all accessories (circumfer-
dynamic mode depending on the kind of modula- ential extent of vacuum cushion or cast, mani-
tion needed (lesser scatter superior and inferior to fold cushions, etc.) are included the CT scan
target with dynamic mode). Pneumatically driven acquired, since contribution from attenuation
binary MLCs (32 pairs) are used for further beam due to beams passing across the entire circum-
shaping and the beam that finally emanates is a ference has to be accounted for. This may require
modulated fan beam. MLC leaf projects to the use of a larger field of view (FOV) than usual,
6.25 mm along transverse axis at isocenter. but efforts should be made to limit the FOV to
6. Beam modifying devices such as wedges and minimum required; too large an FOV will
external shields cannot be used. There is lim- degrade the image quality. The height of the
ited benefit of bolus due to rotational beam. couch should be such that the entire couch width
7. Couch movement is constant throughout treat- is included in the scan. Usually a 10 cm clear-
ment for a given plan, with direction towards ance from the FOV edge ensures this. Multiple
the bore during treatment. Hence treatments LASER alignments apart from fiducials should
that involve below hip irradiation may need be marked on the body to ensure correct position
simulation in feet first position. Also, the reproducibility at treatment.
couch is capable of lateral movement of up to Slice thickness should be uniform through-
2.5 cm on either side and only rotational shifts out, and is generally 2–3 mm. The planning CT
in roll can be corrected besides translational should be extended cranially and caudally
shifts at the time of verification imaging. beyond the target for accurate dose calcula-
tions. This extent may vary from at least 3.5 cm
on either side for gantry width 1 cm and 8.5 cm
25.4 Preparation and Simulation for gantry width 5 cm. As a rule of thumb, scans
Process are extended for 10 cm in either direction. The
rest of the immobilization and simulation pro-
The mould room process should account for the cess (fiducials, contrast administration, bowel/
fact that treatment would be carried out with a bladder protocols) are similar to that used for
closed gantry system with a maximum bore of other LINACs.
25 Plan Evaluation for TomoTherapy 161

The Tomotherapy planning system (TomoPlan) should be delineated as dose-limiting volumes

accepts only raw CT DICOM data. Any third (DLV). DLV should ideally be separated by
party treatment planning system that manipulates 1–1.5 cm from planning target volume (PTV) to
CT images before transfer should not be used. ensure optimum PTV coverage. Ring structures
The existing planning system is not suited for drawn around the PTV at 1–2 cm margin may
extensive contouring nor does it accept any addi- help control dose spill beyond that limit. Partial
tional image sets (MRI, PET, prior CT) for fusion rings around PTV (e.g., different rings towards
with the planning CT dataset. It is used only for skin and towards viscera) may help alter the rate
minor corrections. For the purpose of delineation, of dose fall-off by giving different constraints.
any other contouring workstation can be used and Some of these DLVs may be used to block the
contoured images along with structure sets can be beam projection in that direction (complete or
transferred to planning system. directional) in the planning system. For instance,
periphery of opposite lung may be drawn as
blocking structure for a carcinoma breast case to
25.5 Contouring Tips limit dose to opposite lung and breast. Figure 25.3
illustrates some common contouring scenarios
Target volumes and organs at risk (OARs) are where DLVs are required.
case-­specific and are no different from non-­ If use of bolus is being considered (although
Tomotherapy situations. due to helical delivery, impact is expected to be
Skin or patient body is not required for opti- lower), it should be prepared and included at the
mization by the system but when delineated, it time of simulation to study its true impact. An
helps in limiting/defining other structure dimen- additional image set without bolus should also be
sions and for quantification and control of dose taken to assess the degree of benefit, if at all.
spill during planning by displaying Global dose Rotational treatment delivery minimizes the
maximum outside target. It represents all normal skin sparing effect. Targets too close to the skin
tissue not included in any other contoured may lead to high skin doses, especially with
volume. respiratory motion, and adequate precautions
Contours should be smooth and all efforts should be taken to avoid this. If the PTV contour
should be made to avoid any erroneous or stray extends to skin or outside it, the optimizer will try
volumes. PTV should be limited inside the body hard to push dose into that voxel increasing flu-
contour by at least 1 voxel (2–5 mm depending ence in air, and results in unacceptable hot spots
on site) since the optimizer tries to push dose into even if they are not displayed on the plan image.
every target voxel. Consistency in contour across When drawing multiple targets (cranial and spi-
various slices should be ensured with no sudden nal in CSI, multiple brain metastases, postoperative
jumps in shape or size from one slice to the other. cervix bed and pelvic nodes, breast and supracla-
Since treatment is delivered rotationally, many vicular nodes), control of OAR dose and optimiza-
dose-limiting help structures are needed besides tion within targets is better if they are drawn and
OARs to reduce dose spillage. When there are optimized as separate targets rather than a single
paired OARs in the field (e.g., lungs as OAR for volume even if same dose is being prescribed.
breast cancer), drawing them separately helps
control dose to each of them better than a single
large volume. Also sub-segmentation (dividing 25.6 Planning and Plan
ipsilateral lung into segments that lie closer to the Evaluation
breast and farther from it) also helps refine and
define the dose fall-off. All empty regions (poste- All planning images are down-sampled to
rior neck in head-and-neck radiation, soft tissue 256 × 256 in planning workstation. After import-
between multiple targets in the same vicinity, ing CT images and radiation therapy structure set
e.g., prostate and pelvic nodes in prostate cancer, into planning system and contour correction as
right and left neck PTV in head-and neck-cancer) required, the CT couch is identified and removed
162 S. Goyal and S. Banerjee

a b

c d

Fig. 25.3 Radiotherapy planning images showing the by delineating it separately as DLV. Another coronal sec-
various dose limiting volumes (DLVs) needed for plan- tion of the same patient shows a superior DLV above the
ning a case for tomotherapy. (a) A case of carcinoma heart (7) to reduce dose spillage into mediastinum. (c) A
breast for chest wall and supraclavicular radiation with case of carcinoma prostate with anterior abdominal wall
bolus over chest wall. Contralateral breast (1) can serve as (8) as DLV, a loop of bowel (9) between the right and left
DLV. Opposite side lateral chest wall (2) serves as direc- pelvic nodal target volumes that needs optimized to
tional block to reduce dose spill to right lung. Rest of left reduce dose spillage from both targets. (d) A case of car-
chest wall (3) is another DLV to reduce spillage from high cinoma anal canal with prostatic involvement with target
dose volume in left chest wall target. Left lung is divided volumes including primary site as well and pelvic and
into lateral (4) and medial (5) segments and differential inguinal nodes. The targets are separated by unnamed tis-
constraints may be given to each for dose optimization. sue (11) which needs to be delineated as DLV to prevent
(b) High dose spill to anterior heart (6) and be prevented dose bridges

from the CT scan image, and in its place, the which includes bilateral neck node stations II–IV,
Tomotherapy couch is virtually inserted. This and right tonsillar region with margins, PTV70
step helps account for the treatment couch atten- which includes the gross tonsillar lesion with
uation irrespective of the kind of CT scanner 1 cm margin and gross right level II node with
used. 1 cm margin). The right parotid is partially over-
The contoured structures have to be separated lapping PTV54. Also assume that a part of man-
into targets and OARs. If there are multiple over- dible is within PTV54 and we wish to give it a
lapping structures, the overlapping priority is serial dose constraint (Dmax < 53 Gy). The other
defined for the optimizer. The optimizer always OARs for head and neck may also have a partial
gives a higher weightage to the target. Also, overlap with PTV54. The targets are defined as
among different overlapping volumes, the struc- overlap priority of 1 for PTV70, and 2 for PTV54.
ture with the higher overlap priority (lower In this manner, the optimization for PTV54 hap-
numeric digit) gets more weightage (overlap pri- pens only for the volume outside PTV70. If
ority 1 > 2). For instance, consider a head-and-­ PTV54 were given priority of 1, the optimizer
neck cancer case (carcinoma right tonsil would not consider the other two targets since
T2N1M0) where there are two targets (PTV54 they are completely hidden within PTV54. Now,
25 Plan Evaluation for TomoTherapy 163

for the OARs, the part of the right parotid over- the planning system should be matched to the
lapping with PTV54 would not be considered for fiducial marks. Red LASER (i.e., fiducial slice)
dose optimization. Also, the maximum dose con- can offset ~18 cm from green LASER (i.e., slice
straint for the mandible overlapping with PTV70 that is midway between the superiormost and
cannot be met because it being an OAR has lesser inferiormost sections). This forms the planned
priority than the PTV. For achieving these objec- position.
tives, the PTV may further be divided into non-­ Subsequently treatment delivery mode
overlapping and overlapping parts (PTV54 (Helical or Direct), plan mode (IMRT or 3DCRT),
outside parotid, PTV54-parotid overlap, PTV54-­ field width (1, 2.5 or 5 cm), jaw mode (fixed or
mandible) and they may separately be optimized dynamic), pitch, and image value to density table
with differing objectives (Fig. 25.4). The cumula- (IVDT) are selected. The 3DCRT mode is not
tive dose volume profile of the entire volume can true 3DCRT but represents planning in the static
also be seen on the dose volume histogram gantry mode, which is most commonly used for
(DVH). It is possible to select certain volumes lateralized breast treatments simulating tangen-
only for dose display and not “use” them for opti- tial fields (effect akin to forward planned IMRT).
mization, e.g., right cochlea for a left parotid If 3DCRT is selected, beam angles have to be
malignancy treatment, or spinal cord for an early predefined. Usually a single pair of beams is used
breast cancer treatment. Figure 25.5 details the but some plans may benefit with 2 or 3 pairs as
various planning steps for a case of bilateral well, with dose spill much lesser than helical
breast carcinoma treated with helical tomotherapy despite use of multiple beam pairs.
tomotherapy For the bilateral breast carcinoma plan shown
Tomotherapy room has a set of green and red in Fig. 25.4, helical mode with 2.5 cm jaw width
LASERs. The red LASER intersection corre- and dynamic delivery was selected. Target goals
spond to the machine or bore isocenter, and the and OAR constraints were specified in the opti-
green LASER is 70 cm outwards horizontally, mization window. The detailed planning process
which is called the virtual isocenter. On simula- is given in image description.
tion, the center of the CT scan defaults to the After the dose—volume parameters for a given
green LASER. After the images are imported target are achieved (say at least 95% of target vol-
into Tomoplan, the red LASER as identified by ume received the prescription dose), look for both

a b c d

Fig. 25.4 Carcinoma right tonsil T2N1M0, planned for the target. During optimization, only the part outside
radical radiation (a–c, axial, coronal and sagittal sec- PTV54 is optimized for parotid constraint. To prevent hot
tions). GTV primary (red) and GTV node (dark red) are spots within the overlap region without underdosing tar-
delineated. PTV70 (purple) is 1 cm expansion around get, multiple volumes are generated: PTV54 minus
GTV. PTV54 (orange) is another 5 mm expansion around parotid, PTV54-parotid overlap (magenta) and parotid
PTV70 and also includes bilateral neck node levels II– outside PTV (dark blue) and the first two are optimized as
IV. The overlap priority given to PTV70 is 1 and PTV54 is separate targets. Similarly volume of mandible overlap-
2. During optimization, the part of PTV54 overlapping ping with PTV54 can also be delineated separately and
with PTV70 is not optimized for 54 Gy since it has lesser optimized to reduce hot spots. Posterior neck, oral cavity,
priority than PTV70. (d) Right parotid partially overlaps lips, buccal pad of fat are all delineated as dose limiting
with PTV54.Since it is an OAR, it has lesser priority than volumes (DLVs) to prevent low dose spill
164 S. Goyal and S. Banerjee

►
Fig. 25.5 (a) Bilateral breast cancer CT and RT structure percentage volume parameters can be assessed. Dose dis-
sets imported into Tomoplan. Additional contouring of tribution across all 3 planes can be viewed. The various
DLVs can be performed at this step in “Contouring” tab if dose levels can be customized as per case and planner/
not done already. Note the FOV is large enough and the evaluator preference. Ideally, doses at 100%, 105–107%
couch height optimal to include the entire width of CT and above, 95%, 90%, 50%, 20% of prescription dose are
couch in axial image. (b) Note the axial section where CT visualized in all planes as well as on the DVH to evaluate
couch has been replaced by tomotherapy couch. In the the dose distribution. The target goals are achieved first
ROIs tab, the contoured structures are segregated into tar- and then the constraints for specific OARs may be made
gets and regions at risk. (c) In the plan settings tab, the red more stringent to achieve lower doses. For example, if
LASER is brought to align with the fiducial markings. V20 for lungs is achieved at 20% and V5 at 45%, the opti-
Various plan parameters (helical delivery, IMRT, field mizer may be made to work for achieving V20 of 18% and
width, jaw mode etc.) are specified at this step. Since this V5 of 40%, further optimizing till the target coverage
plan was taken for helical delivery, the beam settings tab starts to reduce. The hot spot region of each target and
(needed for TomoDirect) is not highlighted. (d) The opti- OAR seen as tail on extreme right is to be especially eval-
mization tab requires inputs for all target and OAR dose uated and identified in axial slices. Scrolling over DVH
requirements, Total dose, dose per fraction, percent vol- will give the respective dose level for a given volume and
ume coverage requirement by prescription isodose have to vice versa. (e) The final dose distributing shows a highly
be specified. Overlap priorities have already been defined conformal plan and doses of 107% and above are scat-
earlier but have to be checked here. OAR constraints can tered and amount to less than 2% of total target volume.
be given in terms of maximum and volume dose con- There are no regions of high dose bands or strips. (f)
straints. Up to 3 volume constraints can be given for an When reviewed for low dose regions up to 5 Gy and doses
OAR. “Importance” and “Penalty” for targets and OARs higher than 107% prescription, the true heterogeneity and
are specified in order of importance. The dose volume his- integral dose may be apparent. Optimization is continued
togram at the bottom shows real time dose optimization till a satisfactory plan is achieved. A final check on all low
over several iterations. The colored circles specify the pre- dose distributions away from the target should finally be
scribed goals and the solid lines represent the dose for a made before iteration at fine resolution and final accep-
given volume at that stage of the plan. Both absolute and tance of plan

hot and cold spots and their respective magnitude, After a satisfactory plan is achieved and fine
volume, and location. The optimizer goals with resolution optimization achieves final doses, it is
importance and penalty may be changed to fine- reviewed by clinical and physicist and approved
tune till satisfactory distribution is achieved. A if acceptable. A patient specific delivery quality
cold spot may be acceptable if it is <1% of PTV assurance of all plans is recommended before
volume, receives dose of at least 95% of pre- treatment delivery and a variation of up to 3% is
scribed, and is located in the periphery of PTV acceptable. After approval, the given plan is
(never within clinical target volume, CTV) where available for delivery at the treatment station.
it is unlikely to compromise disease control. A hot
spot volume should ideally be less than 15% of
PTV, located within CTV (preferably within GTV) 25.7 Summary
but never at the periphery of PTV at interface with
OAR, and magnitude ideally less than 115% of The Tomotherapy planning process is fairly
prescription dose, with less than 15% of its volume user-­friendly but involves a lot of effort and
receiving more than 110% prescription dose. foresight to identify possible areas of dose spill
Check for any high dose volumes (more than pre- or low dose spread and then mark these with
scription dose) outside PTV and try to eliminate or dose limiting volumes. It is especially well
at least reduce them. Whenever hot spots are suited for large and complex volumes though
observed at periphery in a tomotherapy plan, not applicable across all teletherapy indications.
review the dose constraints for adjacent OAR and Proper case selection ensures optimal clinical
try to relax them for reducing the hot spots and outcomes. The principles of plan evaluation
then tighten those constraints gradually till satis- remain the same as all other modalities with a
factory distribution emerges. few equipment-specific tweaks.
25 Plan Evaluation for TomoTherapy 165

a b

c d

e f

Source of image Images have been taken from 3. Langen KM, Papanikolaou N, Balog J, Crilly R,
patients treated by author and consent has been Followill D, Goddu SM, Grant W 3rd, Olivera G,
Ramsey CR, Shi C, AAPM Task Group 148. QA for
taken. helical tomotherapy: report of the AAPM Task Group
148. Med Phys. 2010;37:4817–53.
4. Sharma DS, Gupta T, Jalali R, Master Z, Phurailatpam
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T, Mehta M. Tomotherapy. Semin Radiat Oncol. 5. Sarradin V, Simon L, Huynh A, Gilhodes J, Filleron
1999;9:108–17. T, Izar F. Total body irradiation using Helical
2. Smilowitz JB, Dunkerley D, Hill PM, Yadav P, Geurts Tomotherapy: Treatment technique, dosimetric results
MW. Long-term dosimetric stability of multiple and initial clinical experience. Cancer Radiother.
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Le Blanc-Onfroy M, Delpon G, Campion L, Mahé U, Tofani S. Does TomoDirect 3DCRT represent a
MA. Toxicity and early clinical outcomes in cervi- suitable option for post-operative whole breast irra-
cal cancer following extended field helical tomother- diation? A hypothesis-generating pilot study. Radiat
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2010;94:60–6. H. Tomotherapy - a different way of dose deliv-
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F, Aimonetto S, Peruzzo A, Pasquino M, Russo G, 2012;16:16–25.
 Plan Evaluation in LINAC Based
SRS and SABR 26
Prashanth Giridhar

26.1 Salient Points 7. Performance status

8. Treatment intent (Curative vs palliative)
1. In SRT/SRS, the definitions of GTV, CTV, 9. Patient simulation (Immobilization devices,
and PTV have been largely ignored simulation protocols, etc.)
2. Traditionally, prescription has been done to a 10. Description of target volumes (GTV, CTV,
particular isodose PTV) and organs at risk
3. Plan evaluation traditionally included isodose 11. Planning aims and dose volume constraints
coverage instead of dose volume histogram 12. Dose reporting to target and organs at risk
4. ICRU 91 recommends use of dose volume
parameters
5. Absorbed dose at a point is not meaningful in 26.3 Dose Reporting [2, 3]
SRS due to heterogeneity within target
volume The following metrics are to be included in dose
reporting of SRS.

26.2  eporting of SRS Plan

R
Should Include the 26.3.1 Metrics for Target Coverage
Following as per ICRU 91 [1]
1. PTV median absorbed dose (D50%)
1. Brief clinical history Note: If CTV is defined, CTV median absorbed
2. Relevant clinical examination dose is to be reported. In peripheral lung
3. Location of lesion to be targeted with lesions, where the dose distribution is strongly
radiotherapy affected by tissue density, a dose to target (GTV
4. Diagnostic technique used for identification or CTV) that does not include uninvolved lung
of lesion parenchyma should be reported
5. Histological diagnosis 2. SRS PTV D-near max
6. Prior treatment Note: For PTV > 2 cc, report D2%. For
PTV < 2 cc, report D35mm3
3. SRS PTV D-near min
P. Giridhar (*)
Department of Radiation Oncology, All India Institute Note: For PTV > 2 cc, report D98%. For
of Medical Sciences, New Delhi, India PTV < 2 cc, report PTV D (v – 35 mm3)

© Springer Nature Singapore Pte Ltd. 2020 167

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_26
168 P. Giridhar

26.3.2 M
 etrics to Report for Doses 26.4.2 Gradient Index
to Organs at Risk PIVhalf
GI =
PIV
1. Vd
PIVhalf: Prescription isodose volume at half the
Note: Volume of tissue receiving a clinically
prescription isodose; PIV: Prescription isodose
relevant dose
volume
2. Dmean
3. Dmedian
4. SRT D near max (D2% or D35mm3)
26.4.3 Homogeneity Index

Due to huge differences in the dose within the PTV

26.4 I ndices in SRS Plan in stereotactic treatments, a consensus has not yet
Evaluation been reached in defining homogeneity index for
SRS/SABR plans. It is advised to note the D2%
26.4.1 Conformity Index
and D98% for high and low dose, respectively.
There are different conformity indices described.
The most common one used is the Paddick con-
References
formity index. It is given by the formula:
2
TVPIV 1. Prescribing, recording and reporting of stereotactic
Paddick Conformity Index = treatments with small photon beams—ICRU report
TV × PIV No. 91; 2017.
2. UK SABR consortium guidelines version 4.0 January
TVPIV Target volume within the prescription iso-
2013.
dose volume; TV Target volume; PIV Prescription 3. UK SABR consortium guidelines version 5.1 January
isodose volume 2016.
 Part IV
Practical Radiobiology
 Clinical Significance of Cell
Survival Curves 27
Prashanth Giridhar and Goura K. Rath

27.1 Introduction fraction is usually represented in a logarithmic

scale in the cell survival curves. The shape of cell
Cell cycle in a dividing cell consists of two survival curves also depends on the type of radia-
phases—the mitotic (M) phase where the cell tion used. Neutrons and carbon ions which are
actually divides and the S (synthetic) phase where densely ionising show an exponential curve while
the DNA is replicated. These are separated by two X-rays and gamma rays show an initial slope fol-
gaps, the G1 and G2 phases. The time between lowed by a shoulder which again becomes
two successive divisions is called the cell cycle straight (Fig. 27.1).
time. Of these different phases, the G2M phase is Experimental studies on cell lines and clinical
the most radiosensitive while the S phase is the data have helped us in deriving a meaningful cell
least radiosensitive. Cell death of non-proliferat- survival curve. Performing studies on cell lines
ing cells is defined as the loss of specific function and collecting data from clinical studies is often
and for cells capable of many divisions it is cumbersome and time taking.
defined as the loss of reproductive integrity. Mathematical models with a strong biological
Cell death induced by radiation at conventional basis have helped us in understanding and
fractionation is primarily by creation of double explaining this curve. These will help in improv-
strand breaks. Explaining how radiation interacts ing therapeutic ratio by creating dose fraction-
with DNA leading to cell death is beyond the ation schedules with equivalent or higher
scope of this chapter. At higher dose per fraction- biological effective doses. This chapter mainly
ation other processes like endothelial damage and focuses on models explaining the cell survival
immune system stimulation play a role. curve of X-rays (Llow LET).

27.2 Cell Survival Curves 27.3 Mathematical Models

Cell survival curve is used to describe the rela- Older empirical models were derived from past
tionship between the surviving fraction of cells to clinical data and could go disastrously wrong if
radiation and the absorbed dose. The surviving used outside the dose fractionation they were
derived from. These include the cumulative radi-
ation effect model (CRE), nominal standard dose
P. Giridhar (*) · G. K. Rath
Department of Radiation Oncology, All India Institute model (NSD), time dose fractionation model
of Medical Sciences, New Delhi, India (TDF) and tumour significant dose model (TSD).

© Springer Nature Singapore Pte Ltd. 2020 171

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_27
 172 P. Giridhar and G. K. Rath

CELL SURVIVAL CURVE The probability to produce such a damage is

proportional to dose. This is called the alpha
component.
• The second type of damage, responsible for
the quadratic component, is by itself not lethal
log Survival Fraction

xr
for the cell. This is called sublethal damage.

ay
Only combination of two such lesions can
LOW LET
yield a lethal event for the cell. The probabil-
ne

ity to produce a single sublethal damage is

utr

again proportional to dose. The probability to

on

produce two of such lesions is proportional to

HIGH LET
the square of dose. This constitutes the beta
component.

The survival at a given radiation dose is due to

Dose
a combination of alpha and beta killing and can
Fig. 27.1 Representative image of cell survival curve. be represented by the following formula:
Note that the cell survival curve of neutrons is a straight
S ( D ) = e −α D − β D
2

line while that for X-rays the survival curve has an initial
slope followed by a shoulder and then becomes a straight
line S: Surviving fraction at dose D; D: Dose
The above formula works well for single frac-
The failure of these models led to creation of the tion treatments. When the treatment is fraction-
linear quadratic model (LQ). ated and protracted, a time factor has to be
included in the formula to account for dose rate
and also the rate of damage repair during this
time. This modification called the generalised
27.4 The Linear Quadratic Model
time factor (G) was provided by Lea and
Catcheside.
The LQ model is a mechanistic, biologically
based model. It has sufficiently few parameters to S = exp  − (α D + G β D 2 )  .
be practical. It is reasonably well validated exper-
imentally and theoretically. The model makes a G: Generalised time factor
few assumptions to work well. The assumptions
include:
27.4.1 T
 he Alpha by Beta Ratio
1. Cell killing is primarily a result of DNA dam- and Its Implication
age (double strand breaks) in Radiation Oncology
2. For multifractionated treatment, the fractions
are well separated in time The radiation dose at which the alpha killing
3. Irradiation time for EBRT is short and with a (lethal) is equal to beta killing (combinations
constant dose rate of sublethal killing leading to lethal killing) is
called the alpha by beta ratio. Its unit is Gray.
The LQ model considers two types of radia- Cells with poor repair capability (e.g. tumours)
tion damage: tend to develop more lethal damage than cells
with good repair capability (e.g.: Late respond-
• The first type of damage, responsible for the ing normal tissue). This leads to a higher
linear component, is assumed to result from a alpha/beta ratio for tumours with a straighter
single event. This damage is lethal for the cell. cell survival curve than late responding tissue
27 Clinical Significance of Cell Survival Curves 173

Fig. 27.2 Difference in

cell survival curve
between early (tumour)
alpha/beta = 4
and late responding 1.0
tissue as explained by alpha/beta =10

Survival fraction (log scale)

LQ model
Straighter survival curve

Early
responding
tissues
Late
responding
tissues
A
Curved survival curve

0 10 20 30
Dose (Gy)

AS TUMOUR HAS ALPHA BY BETA OF 11, ASSUME THE DOSE PER Damage to OAR becomes prohibitively high decreasing the
FRACTION AS 12 Gy therapeutic ratio
1.0
Surviving fraction (log scale)

PATIENT BODY Surviving fraction of tumour

Alpha/beta = 4 Early
ORGAN AT RISK
responding
tissues
Late
responding
Alpha/beta = 11 tissues
TUMOUR A
ORGAN AT RISK 2 Surviving fraction of OAR
4 12 Gy dose per fraction
3 B
ORGAN AT RISK 3

0 10 20 30

Dose (Gy)

Fig. 27.3 Effect of different tissues with different alpha/beta ratios as explained on cell survival curves

(Fig. 27.2). This difference in cell survival with a lower alpha by beta ratio tends to get
curves provides rationale for fractionated radi- damaged more. This phenomenon is pictorially
ation therapy treatment. depicted in Fig. 27.3 for better understanding.
The alpha by beta ratio for most tumours is Alpha/beta ratio of different tissues is sum-
10 or higher with prostate and breast cancers marised in Fig. 27.4.
being the exceptions (<3). The alpha by beta The classical LQ model described above has
ratio is the dose at which the survival curve the following limitations:
bends and killing tends towards exponential.
Therefore, adopting a dose per fraction more 1. It does not include the effect of redistribution
than the alpha by beta ratio will kill more cells and reoxygenation in a protracted treatment
than when dose per fraction is less than the course
alpha by beta ratio for the same given total 2. The cell survival curve predicted by the LQ
dose. This seems practically feasible only in model is continuously bending but in reality,
tumours with a low alpha by beta ratio as nor- the cell survival curve becomes linear at
mal late responding tissue around the tumour higher doses
174 P. Giridhar and G. K. Rath

Early-Responding Tissues a/b Late-Responding Tissues a/b b

Jejunal mucosa 13 Spinal cord 1.6–5

(110, 166, 245, 284, 285, 322)
Colonic mucosa 7 Kidney (44, 127, 291, 305) 0.5–5
Skin epithelium 10 Lung 1.6–4.5
(90, 211, 214, 275, 289, 295)
Spermatogenic cells 13 Liver (91) 1.4–3.5
Bone marrow 9 Human skin 1.6–4.5
(32, 211, 279, 280)
Melanocytes (302) 6.5 Cartilage and submucosa 1.0–4.9
(171, 329)
Tumors
Mouse fibrosarcoma metastases (173) 10 Dermis (106) 2.5 +
_ 1.0
Human tumors (169, 171, 195, 258) 6–25 Bladder (252, 265) 5.0–10.0
Experimental tumors (306) 10–35 Bone (212) 1.8–2.5

Fig. 27.4 Alpha/beta ratio of different tissues

3. Robust clinical data is missing for LQ model proposed to circumvent problems in the era of
validity at high dose per fraction (>10 Gy) SRS and SBRT:

The solutions to the above limitations are 1. Universal survival curve

explained in brief in the next section. 2. LQL model

27.5 The LQR Model 27.7 Universal Survival

Curve (USC) Model
The LQR model is an extension of LQ model to
account for redistribution and reoxygenation. It The USC model combines the LQ model and mul-
regards both the processes by a single term called titarget model. The multitarget model states that
re-sensitisation. This model adds two parameters multiple targets are hit for cell killing after radia-
to the LQ formalism—re-sensitisation magnitude tion. As there is no clear biological basis for the
and re-sensitisation time. It assumes that the above statement at low doses (DNA is the ­target),
re-­
­ sensitisation is monotonic i.e. it always the multitarget model was not universally accepted.
increases the radiosensitivity of tissues. But at higher doses, with endothelium and immune
Explaining the LQR model in detail is beyond the cells also becoming targets for tumour cell kill, the
scope of this chapter and readers are requested to multitarget model started getting importance. The
refer to the original article by Brenner et al. on USC model uses the LQ model for survival predic-
LQR model [1]. tion at low dose per fractions and the multitarget
model for higher dose per fraction. By combining
the two models, the curve predicted at higher doses
27.6 Models for High is straighter and more in line of experimental data.
Dose per Fraction The model introduced two terms i.e. surviving
fraction equivalent dose (SFED) and standard
The LQ model fails at high dose fractionation effective dose (SED). Explaining the USC model
and due to continuously bending curve predicted in detail is beyond the scope of this chapter and
by it, the model overestimates the killing at readers are requested to refer to the original article
higher doses. The following models have been by Park et al on USC model [2].
27 Clinical Significance of Cell Survival Curves 175

As all processes involved in cell killing at v­ enturing into formulae and technical terms. We
higher doses have not been completely eluci- encourage the readers to go through the original
dated, it is difficult to decide on the most suit- articles of LQ, LQR and USC models.
able model to be used in doses used in SBRT
and SRS.
References
1. Brenner DJ, Hlatky LR, Hahnfeldt PJ, Hall EJ, Sachs
27.8 Conclusion RK. A convenient extension of the linear-quadratic
model to include redistribution and reoxygenation. Int
Understanding the cell survival curve and the J Radiat Oncol Biol Phys. 1995;32(2):379–90.
basics of mathematical models predicting cell 2. Park C, Papiez L, Zhang S, Story M, Timmerman
RD. Universal survival curve and single fraction
survival is of utmost importance for radiation equivalent dose: useful tools in understanding potency
oncologists. This chapter provides only insights of ablative radiotherapy. Int J Radiat Oncol Biol Phys.
into various mathematical models without 2008;70(3):847–52.
 6Rs of Radiation Oncology
28
Renu Madan and Divya Khosla

Radiotherapy is an integral part of cancer treat- The 6Rs are described below:
ment in most of the solid malignancies. The basic
principle is to deliver maximum dose to the target 1. Repair or recovery of sublethal damage: Cell
while sparing normal tissues as much as possible. kill by ionization radiation happens because
Total dose, dose per fraction, overall treatment of the DNA double strand breaks (DSB).
time, time interval between fractions, intrinsic Ionization radiation causes two types of DNA
radiosensitivity, and dose rate are the important damage, non-repairable or lethal and repair-
factors affecting therapeutic ratio. 4Rs of able or non-lethal. Most of the radiation
Radiotherapy is a well established term and was induced DNA damage is sublethal and gets
initially described almost 50 years back for better repaired at lower doses. But at higher doses
understanding of time dose and fractionation in multiple sublethal damages can convert into
radiotherapy. These 4Rs are repair of sublethal lethal damage. High dose will lead to
damage in normal tissues, reoxygenation of the increased tumor cell kill as well as increased
tumor cells, redistribution of the tumor cells in normal tissue toxicity. It is believed that
more radiosensitive phase, and repopulation of tumor cells have slower recovery as com-
tumor and normal cells. Dividing a dose into sev- pared to normal cells. Thus when a gap is
eral fractions will spare normal tissue due to repair given between the two doses of radiation,
of sublethal damage and repopulation of the cells normal cells recover fast as compared to
if time between the two fractionation is sufficiently tumor cells. However excessive prolongation
long. At the same time tumor damage will be may repair tumor cells as well.
higher due to reoxygenation and reassortant or 2. Redistribution: Radiation sensitivity of vari-
redistribution of the cells in more radiosensitive ous cells depends on the cell cycle phase.
phase (G2/M). Later on the concept of 4Rs was Cells in mitosis (M) or G2 phase are most
changed to 6Rs. Radiosensitivity and remote radiosensitive while least radiosensitive in
(bystander effect), are the 5th and 6th R respec- G1/S phase (DNA synthetic phase) [1]. When
tively. These 6Rs are the basis of time dose and a single large dose of radiation is given, the
fractionation in radiotherapy. surviving cells are most likely to be in a radio-
resistant phase thus the immediate second
dose may not be effective. The next fraction
R. Madan (*) · D. Khosla
after a gap may allow the surviving cells to
Department of Radiotherapy and Oncology, Post
Graduate Institute of Medical Education shift to more radiosensitive G2/M phase
and Research, Chandigarh, India which may lead to increased cell killing [2].

© Springer Nature Singapore Pte Ltd. 2020 177

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_28
178 R. Madan and D. Khosla

3. Reoxygenation: Effect of radiotherapy is more thought the radiation exposure leads to target
profound in the presence of oxygen. In hypoxic cell killing. However remote bystander effect
conditions, the chemical changes in the target contradicts this thought and cells that are actu-
get repaired while presence of oxygen leads to ally not exposed to radiation also show sign of
irreparable and permanent damage [3]. radiation damage [7]. This happens when radi-
Percentage of hypoxic cells in a tumor ranges ation hit cell sends damage signals to non-tar-
from 10 to 15% and generally it is the central get cells by gap junction. This effect has been
part of the tumor which is hypoxic. Acute seen in both normal and tumor cells which
hypoxia can be because of blockage of a blood may also have some clinical implication.
vessel while chronic hypoxia can be because
of the limited diffusion of oxygen in the tis- These Rs are very important in determining
sues. Any given tumor is a mixture of oxic and time dose and fractionation of radiotherapy. In
hypoxic cells. Acute hypoxia is not permanent any given situation there must be an optimal
as the blood vessels open and close intermit- combination of
tently. Thus when 1st dose of radiation is
given, the oxygenated cells will be killed. But (a) Total dose
as hypoxia is not permanent, when next dose (b) Dose per fraction
of radiation is given, hypoxic cells may get (c) Time interval between fractions
reoxygenation and thus can be killed [4]. (d) Overall treatment time
4. Repopulation: It is described as cell division (e) Intrinsic radiosensitivity
in normal and tumor cells after a certain time (f) Dose rate à brachytherapy
of radiation. Rapidly dividing tissues such as
skin, mucosa, and bone marrow are likely to
experience more acute toxicity which happens
as a result of balance between the cell killing References
and cell regeneration [5]. Thus delay in the
1. Cox JD, Ang KK. Radiation oncology: rationale, tech-
radiation treatment is actually better than the nique, results. 8th ed. St. Louis, MO: Mosby Elsevier;
treatment interruption due to any reason 2002.
because of the accelerated repopulation. 2. Harrington K, Jankowska P, Hingorani M. Molecular
Mitotic catastrophe: Tumor repopulation biology for the radiation oncologist: the 5 Rs of radio-
biology meet the hallmarks of cancer. Clin Oncol.
during radiotherapy is considered as an unde- 2007;19:561–71.
sired phenomenon. However it can some- 3. Fyles A, Milosevic M, Hedley D, Pintilie M, Levin W,
times lead the cells to be more radiosensitive Manchul L, Hill RP. Tumor hypoxia has independent
as more cells enter into mitosis with unre- predictor impact only in patients with node-negative
cervix cancer. J Clin Oncol. 2002;20:680–7.
paired DNA [2]. 4. Nordsmark M, Bentzen SM, Rudat V, Brizel D,
5. Radiosensitivity: intrinsic radiosensitivity is a Lartigau E, Stadler P, Overgaard J. Prognostic
feature of tumor which is why few tumors value of tumour oxygenation in 397 head and
respond very well to the radiation while few neck tumors after primary radiation therapy: an
international multi-­centre study. Radiother Oncol.
do not respond at all. Concept of intrinsic 2005;77(1):18–24.
radiosensitivity arises from genetically insta- 5. Suwinski R, Sowa A, Rutkowski T, Wydmanski J,
bility of the tumor cells [6]. Activation of Tarnawski R, Maciejewski B. Time factor in postop-
EGFR (epidermal growth factor receptor), erative radiotherapy: a multivariate locoregional con-
trol analysis in 868 patients. Int J Radiat Oncol Biol
p53 and Ki 67 protein signalling cascade is Phys. 2003;56:399–412.
the important pathways relevant to intrinsic 6. Begg A. Molecular targeting and patient individu-
radiosensitivity. alization. In: Joiner M, van der Kogel A, editors.
6. Remote bystander effect: This occurs when Basic clinical radiobiology. 4th ed. London: Hodder
Arnold; 2009.
non-irradiated cells, situated in the close vicin- 7. Mothersill C, Seymour CB. Review: Radiation-­
ity of the irradiated cells undergo similar cel- induced bystander effects: past history and future per-
lular changes as irradiated cells. Earlier it was spectives. Radiat Res. 2001;155:759–67.
 Radiosensitizers
and Radioprotectors 29
Renu Madan

29.1 Introduction by radiation. Radiosensitizers are the products

that are used to enhance radiation damage to
Radiation therapy is commonly used in most of tumor cells [1]. These agents are collectively
the solid malignancies in neoadjuvant, adju- known as radiation modifiers.
vant, definitive, or palliative setting. It damages
tumor cells by either direct action (direct DNA
damage) or by indirect action (DNA damage by 29.2 Radiosensitizers
means of free radicals). The goal of radiation
therapy is to widen therapeutic ratio by deliver- Radiosensitizers enhance the tumor cell killing
ing maximum dose to the tumor while at the without having any altered response of radia-
same time avoiding excessive radiation dose to tion on normal tissue. Radiation dose can be
normal tissues to reduce the side effects. reduced depending on the extent of sensitiza-
Despite the availability of advanced radiother- tion. Thus therapeutic ratio is widened with
apy techniques, normal tissue irradiation similar tumor control and reduced normal tis-
always happens. sue toxicity.
Although most of the cancer, i.e. head and The mechanism of action is mentioned
neck, cervix, prostate, and lymphoma show good below [2]:
response to radiation, there are many cancers
which show intrinsic radioresistance, i.e., sar- 1. Direct enhancement of radiosensitivity of
coma, melanoma, etc. Radioresistance due to tumor cells
hypoxia is also a major issue. Therapeutic ratio 2. Independently cause DNA damage or inhibit
can be widened by using agents that selectively DNA double strand break repair
sensitize the tumor cells to radiation while pro- 3. Disruption of cell survival pathways
tecting the normal tissues from radiation. 4. Target vasculature of tumor cells
Radioprotectors are the compounds that are used 5. Improve oxygenation or selectively act on
to decrease the damage to normal tissue caused hypoxic cells
6. Direct cytotoxic action, thus reduce the num-
ber of tumor cells required to be killed by
R. Madan (*)
Department of Radiotherapy and Oncology, Post
radiation
Graduate Institute of Medical Education 7. Redistribution of the cells in more radiosensi-
and Research, Chandigarh, India tive phase

© Springer Nature Singapore Pte Ltd. 2020 179

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_29
180 R. Madan

29.3 Various Radiosensitizing Nimorazole also has a better safety profile and
Agents Are Described Below thus high dose can be used. Nimorazole has
shown to improve 5 year loco-regional control in
Hyperbaric Oxygen Therapy (HOBT) As we head and neck cancer as compared to placebo [7].
know hypoxic cells are radioresistant, numerous
trials have been conducted to manipulate hypoxic Tirapazamine Tirapazamine is an agent which
environment of tumor cells but most of them are is selectively cytotoxic to hypoxic cells. Under
inconclusive. Increased oxygen tension in tumor hypoxic conditions it reduces to highly reactive
cells just before radiotherapy may lead to product leading to DNA damage. It has been
increased production of free radicals resulting in studied in lung and head and neck cancer. Side
cellular damage. However it is cumbersome to effects can be nausea, muscle cramps, and hema-
put the patient in high pressure oxygen tank tological toxicities [8]. Mitomycin-C also has
before each fraction of radiotherapy. Use of selective cytotoxicity to hypoxic cells. It is a bio-
HOBT was started almost 50 years back in a clin- reductive alkylating agent and has been studied
ical trial by Churchill–Davidson and Foster et al. in pancreatic and head and neck cancer.
[3]. Subsequent trials showed improvement in
cervical and head and neck cancer patients using Hyperthermia Chronically hypoxic cells with
HOBT. In a meta-analysis of 32 trials using a low intracellular Ph and cells in S-phase of
HOBT in head and neck cancer, improved local cell cycle are considered as radio resistant and
control did not turn into improved survival [4]. are more susceptible to thermal killing.
Following are the mechanism of cell killing by
Carbogen Other strategy to improve oxygen hyperthermia [9]:
tension in tumor cells is breathing carbogen
which is a mixture of 95% oxygen and 5% car- 1. Hyperthermia increases the fluidity of
bon dioxide at atmospheric pressure. It does not membranes
produce vasoconstriction as with 100% oxygen. 2. Inhibits the metabolism
It is a simple procedure as compared with HOBT 3. Inhibition of DNA, RNA, and protein
[5]. Carbogen is believed to overcome chronic 4. Inhibition of DNA repair
hypoxia and is generally used in combination 5. Inhibition of repair of sublethal and poten-
with Nicotinamide that overcomes acute hypoxia. tially lethal cellular damage.
Nicotinamide is an inhibitor of Poly ADP Ribose
polymerase I which repairs single strand DNA Chemotherapeutic Agents Radiosensitization
break. However results are disappointing in clini- by chemotherapeutic agents is because of various
cal practice. mechanisms. Cisplatin, carboplatin, taxanes, and
5FU are commonest radiosensitizers used with
Metronidazole and Its Analogs Metronidazole radiotherapy in cervix, head and neck, esophageal
and its analogues such as misonidazole, etanida- and lung cancer. Nedaplatin, approved in Japan, is
zole, and nimorazole have been shown to increase also radiosensitizer but less nephrotoxic as com-
radiosensitivity of hypoxic tumor cells [6]. These pared to cisplatin. Cisplatin produces single strand
agents are selectively activated in hypoxic envi- breaks by creating inter- and intrastrand DNA
ronment and act as oxygen and stabilize DNA so adducts. These single strand breaks are converted
that it does not get repaired. Misonidazole deplete to lethal double strand breaks by radiation.
sulfhydryl groups in cells and thus inhibiting gly- Concurrent chemoradiotherapy has shown to be
colysis and the repair of radiation-induced dam- more effective in cervix, head and neck, esopha-
age. Use of misonidazole may lead to CNS side geal and lung cancer as compared to radiotherapy
effects. Etanidazole crosses the blood–brain bar- alone. Due to the synergistic action of cisplatin
rier in limited extent and thus CNS side effects and radiotherapy, a lower dose of each can be
are lesser. used which would be otherwise insufficient to
29 Radiosensitizers and Radioprotectors 181

cause cell death if administered alone. The syner- therapy, but the exact mechanism of action is
gistic effect of cisplatin and radiotherapy is due to under investigation.
below mentioned mechanisms:
Thymidine analogs The thymidine analogs
1. Increased binding of toxic platinum interme- bromodeoxyuridine and iododeoxyuridine have
diates in the presence of radiation-induced been used as radiosensitizers in a battery of can-
free radicals cers including head and neck cancers, malignant
2. Radiation-induced increased cisplatin uptake gliomas, brain metastases, soft tissue sarcomas,
3. Cell cycle disruption intrahepatic cancers, and cervical cancers. These
4. Inhibition of repair of radiation-induced DNA agents produce radiosensitization by incorporat-
damage. ing themselves in DNA that increases the DNA
susceptibility to single strand breaks from
5 Fluoro-Uracil (5FU) 5FU is one of the most radiation-­produced free radicals. However, the
common drugs used for colorectal cancer treat- adverse effects such as myelosuppression and
ment and breast cancer. It is an anti-metabolite toxicity in the irradiated area are a concern.
agent. It also causes radio-sensitization by
impairing double strand break repair during the S Hydroxyurea It causes cytotoxicity by inhibit-
phase and by acting as free radical scavenger. ing ribonucleotide reductase, an enzyme respon-
However, as it is particularly toxic to dividing sible for the transformation of ribonucleotides to
cells, clinical use is limited by its severe side deoxyribonucleotides. It is often used to treat
effects on normal cells. For locally advanced rec- hematologic malignancies and myeloprolifera-
tal cancer, preoperative 5FU or capecitabine is tive disorder [11]. Its use as a radiosensitizer is
now considered as the standard of care because investigated since 1960s in patients with head
of the decreased local recurrence rate and and neck cancer, malignant glioma, and cervical
improved survival with addition of 5FU. cancer. Since it has no cytotoxicity for these
tumors, any positive result is assumed to be
Taxanes (Paclitaxel and Docetaxel) Taxanes because of radiosensitization.
are microtubule stabilizers and act as radiosensi-
tizer by arresting the cells in G2-M phase. Membrane Active Agent Cell membrane is
also a critical target for cell killing. Drugs such as
Topoisomerase Inhibitors: Irinotecan It is a local anesthetic (procaine and lidocaine hydro-
camptothecin derivative that has its cytotoxic chloride) and tranquilizers (chlorpromazine)
effect by targeting topoisomerase I. In addition to interact with cell membranes and alter their struc-
having direct cytotoxic effect, these agents have tural and functional organization. These drugs
excellent radiosensitization property that may have been observed to increase the radiosensitiv-
lead to increased cell killing by radiation. ity in Escherichia coli under hypoxic conditions.
Combination of topoisomerase inhibitors and These drugs have been observed to enhance
radiation is a new promising approach. radiosensitivity of hypoxic mouse lymphoma
cells while radioprotection of these cells was
Gemcitabine Gemcitabine is effective as a sin- seen under euoxic conditions.
gle agent in variety of solid tumors. The mecha-
nism of radiosensitization by gemcitabine is not Sulfhydryl Group Suppressor Intracellular
clear [10]. However preliminary studies have compounds containing sulfhydryl (thiol) groups
shown that the radiosensitization with gem- are known to have radioprotective properties.
citabine is not because of increase in the radiation-­ Thus depletion of these compounds may
induced DNA double strand breaks. It is said that increase the radiosensitivity. Glutathione is the
probably gemcitabine induced radiosensitization major intracellular sulfhydryl compound.
is due to apoptosis of the cells undergoing radio- N-Ethylmaleimide, diamide, and diethylmaleate
182 R. Madan

deplete the glutathione level and thus increase Mechanism of Action of Radioprotectors
radiosensitivity. Decrease in the glutathione Majority of these agents prevent DNA damage by
content also inhibits the repair of single strand scavenging free radicals. Radioprotectors should
DNA breaks under aerobic conditions [12]. have the capacity of entering the nucleus of the
cell and to reside near the DNA because free radi-
PARP inhibitors are also believed to increase cals have very short life and range [2].
radiosensitization by targeting DNA damage,
endothelium, and tumor vasculature in pre-­clinical Although many agents have been identified as
studies. However, implementation of these results radiation protectors in preclinical stages, only
in actual clinical scenario is not known yet. Amifostine and Nitroxides have been found to be
useful. In clinical setting only, Amifostine is the
FDA approved agent; however, tumor protection
29.4 Radioprotectors is a controversial issue with this. Antioxidants
also have shown to have some radioprotector
Other than sensitizing the tumor cells to radia- properties [13].
tion, protection of normal tissues from radiation
injury is also an approach to widened therapeutic Amifostine (WR-2721) It is the most widely
ratio. Radiation protectors protect normal tissue used radioprotector as it has been shown to
from deleterious effect of radiation, making a concentrate less in tumor tissue as compared to
potential for radiation escalation and thus normal tissue probably due to tumor acidosis
improvement in therapeutic ratio. Both acute and and lower expression of alkaline phosphatase
late toxicities can be reduced as these agents limit in tumor cells. It is known to induce hypoxia in
the initial extent of tissue damage. the tumor cells and causes DNA condensation
Radiation exposure to normal tissue is an [14]. It is an inactive drug and converts to
inevitable event which may lead to a battery of active thiol by dephosphorylation by alkaline
side effects ranging from mild symptoms to life phosphatase in normal endothelium. In the
threatening complications. Radiation related dephosphorylated state, it enters into the cells
toxicity depends on many factors such as dose, and scavenges free radicals responsible for tis-
volume fractionation, overall treatment time, sue injury. Studies have shown that it signifi-
and intrinsic radiosensitivity. Although advanced cantly reduces moderate to severe xerostomia
radiation techniques such as Intensity Modulated in head and neck patients who receive post-
Radiotherapy (IMRT), image-guided radiother- operative radiotherapy. Other than xerostomia,
apy, and proton radiotherapy have been shown to it also protects lungs, bone ­ marrow, heart,
reduce these toxicities, intrinsic radiosensitivity intestines, and kidneys and provides protection
of the cells is a component which cannot be in cisplatin induced nephrotoxicity, ototoxic-
taken care with these technologies. This is why ity, and neuropathy and cyclophosphamide
radioprotectors are important. induced hematologic toxicity. However 2008
Radioprotector agents should have the follow- ASCO guidelines state that due to concern of
ing characteristics: tumor protection, the routine use of amifostine
in these settings is not recommended. Side
1. It should not protect tumor cells effects of amifostine can be hypotension, nau-
2. It should have minimal toxicity sea, vomiting, dizziness, sneezing, hot-flashes,
3. Easy administration. hypocalcemia, and mild somnolence.
29 Radiosensitizers and Radioprotectors 183

Antioxidants as Radioprotectors As side effects 3. Churchill-Davidson I, Foster CA, Wiernik G, Collins

of radiotherapy imitate oxidative damage, antioxi- CD, Pizey NC, Skeggs DB, et al. The place of oxygen
in radiotherapy. Br J Radiol. 1966;39(461):321–31.
dants (Vitamin A, C, E, glutathione, lipoic acid) 4. Overgaard J. Hypoxic modification of radiotherapy
are believed to protect the normal cells against in squamous cell carcinoma of the head and neck—
radiation [15]. Nitroxide also has unique antioxi- a systematic review and meta-analysis. Radiother
dant properties and is another promising agent for Oncol. 2011;100(1):22–32.
5. Mendenhall WM, Morris CG, Amdur RJ, Mendenhall
future use as radiation protectors. However as with NP, Siemann DW. Radiotherapy alone or combined
amifostine, there is a risk of tumor protection due with carbogen breathing for squamous cell carcinoma
to non-selective free radical scavenging. The use of the head and neck: a prospective, randomized trial.
of antioxidant vitamins during the course of radio- Cancer. 2005;104(2):332–7.
6. Brown JM. Selective radiosensitization of the
therapy was associated with poor tumor control in hypoxic cells of mouse tumors with the nitroimid-
head and neck cancers. azoles metronidazole and Ro 7-0582. Radiat Res.
Superoxide dismutase (SOD) is an antioxi- 1975;64(3):633–47.
dant enzyme which is present in human cells. 7. Overgaard J, Hansen HS, Overgaard M, Bastholt L,
Berthelsen A, Specht L, et al. A randomized double-­
Ionizing radiation leads to formation of highly blind phase III study of nimorazole as a hypoxic
reactive superoxide radicals that has a potential radiosensitizer of primary radiotherapy in supraglottic
of cellular damage. SOD acts as an antioxidant larynx and pharynx carcinoma. Results of the Danish
and catalyzes the conversion of superoxide to Head and Neck Cancer Study (DAHANCA) Protocol
5-85. Radiother Oncol. 1998 Feb;46(2):135–46.
oxygen and hydrogen peroxide. Animal models 8. Lee DJ, Trotti A, Spencer S, Rostock R, Fisher C,
have been used for gene therapy to increase von Roemeling R, et al. Concurrent tirapazamine and
SOD expression in tissue expected to receive radiotherapy for advanced head and neck carcino-
radiation [16]. mas: a Phase II study. Int J Radiat Oncol Biol Phys.
1998;42(4):811–5.
Melatonin is also an antioxidant and increases 9. Horsman MR, Overgaard J. Hyperthermia: a
the expression of antioxidant enzymes i.e. SOD potent enhancer of radiotherapy. Clin Oncol.
and glutathione peroxidase. 2007;19(6):418–26.
10. Catimel G, Vermorken JB, Clavel M, de Mulder
P, Judson I, Sessa C, et al. A phase II study of
Alpha-Tocopherol/Vitamin E (Vit E) VE con- Gemcitabine (LY 188011) in patients with advanced
taining gargles before radiotherapy and 8–12 h squamous cell carcinoma of the head and neck.
after radiotherapy has been shown to reduce the EORTC Early Clinical Trials Group. Ann Oncol.
incidence of oral mucositis in patients who 1994;5(6):543–7.
11. Donehower RC. An overview of the clinical experi-
received radiotherapy for oral cavity and oropha- ence with hydroxyurea. Semin Oncol. 1992;19(3
ryngeal cancers. Suppl 9):11–9.
12. Hayon E, Simic M. Radiation sensitization reactions
Radiation Mitigators These are the agents that of N-ethylmaleimide with model compounds. Radiat
Res. 1972;50(3):464–78.
function after initial exposure to radiation and 13. Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna
thus limit late radiation injury such as fibrosis. MC, Mitchell JB. Radioprotectors and mitigators of
Pentoxifylline and vitamin E are the examples radiation-induced normal tissue injury. Oncologist.
which have been used to treat cutaneous fibrosis 2010;15(4):360–71.
14. Purdie JW, Inhaber ER, Schneider H, Labelle
after breast radiotherapy. JL. Interaction of cultured mammalian cells with
WR-2721 and its thiol, WR-1065: implications for
mechanisms of radioprotection. Int J Radiat Biol
Relat Stud Phys Chem Med. 1983;43(5):517–27.
15. Shirazi A, Mihandoost E, Mahdavi SR, Mohseni
References M. Radio-protective role of antioxidant agents. Oncol
Rev. 2012;6(2):e16.
1. Begg AC, Stewart FA, Vens C. Strategies to improve 16. Guo H, Seixas-Silva JA, Epperly MW, Gretton
radiotherapy with targeted drugs. Nat Rev Cancer. JE, Shin DM, Bar-Sagi D, et al. Prevention of
2011;11(4):239–53. radiation-­induced oral cavity mucositis by plasmid/
2. Citrin DE, Mitchell JB. Altering the response to liposome delivery of the human manganese super-
radiation: sensitizers and protectors. Semin Oncol. oxide dismutase (SOD2) transgene. Radiat Res.
2014;41(6):848–59. 2003;159(3):361–70.
 Altered Fractionation
Radiotherapy 30
Supriya Mallick and Goura K. Rath

Radiation therapy is an important component in 30.1 Hyper-Fractionation

the multimodality treatment of various tumors.
The evolution of concept of fractionation was • In hyper-fractionation, radiation is delivered
one of the major landmarks which helped in the in smaller dose per fraction [1.2–1.5 Gy/#]
safe delivery of radiation. The concept of frac- with two or three fractions delivered every day
tionation was developed by Thor Stenbeck who with a gap of 6 h between fractions.
used small doses of radiation each day to cure Radiobiologically it uses the better ability of
skin cancer and later by Coutard who showed normal cells to repair injury than tumor cells
that protracted fractionation schedule results in • More helpful for tumors with higher α/β ratio
better tumor control as well as reduced skin and than that for the dose-limiting, late-­responding
mucosal toxicity. With better understanding of normal tissue
4 Rs of radiobiology, radiobiology behind dif- • Hyper-fractionation also helps in increased
ferent fractionation schedule was known. In tumor kill by cell-cycle redistribution
conventional fractionation radiation therapy • In addition reduction of the fraction size from
each fraction consists of 1.8–2.0 Gy and is 2.0 Gy to 1.1–1.2 Gy permits a dose escalation
delivered once daily for 5 days a week. The to 7–17%
treatment is usually delivered over a period of • Head and neck cancers have shown the maxi-
6–7 weeks. Hyper-fractionation, accelerated mum clinical benefit with hyper-fractionation-­
fractionation, hypo-fractionation, or a combi- survival benefit of 8% at 5 years in the
nation or hybrid fractionation are the common MARCH meta-analysis [2]
altered fractionation schedules used clinically • Major limitation-logistic reasons in imple-
[1]. A comparison of various fractionation menting the twice daily schedule
schedules is summarized in Table 30.1. • Summary of few trials which evaluated hyper
fractionation in head and neck malignancies is
summarized in Table 30.2

30.2 Accelerated Fractionation

Radiobiological basis: accelerated repopulation

S. Mallick (*) · G. K. Rath
Department of Radiation Oncology, National Cancer is one of the major hurdles for improving tumor
Institute-India (NCI-India), Jhajjar, Haryana, India control. Accelerated repopulation occurs after a

© Springer Nature Singapore Pte Ltd. 2020 185

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_30
186 S. Mallick and G. K. Rath

Table 30.1 Comparison of various fractionation schedules

Overall Acute
Radiobiological basis treatment time Dose per # Total dose toxicity Late toxicity
Hyper Normal tissues have Usually Same 1.2– Increased Increased Decreased
fractionation better repair mechanism 1.5 Gy/# by 7–17%
than tumor
Also re-oxygenation,
redistribution
Accelerated To prevent accelerated Decreased 1.8–2 Gy/# Same or Increased Same/
fractionation repopulation decreased increased
Hypo-­ Useful in tumors with Decreased >2.2 Gy/# Decreased Same Increased
fractionation low alfa/beta

Table 30.2 Summary of few trials comparing conventional vs. hyper fractionation in head and neck malignancies
Number of
Nature of trial patients Outcome Toxicity
RTOG 9003 Randomized 1076 Survival benefit with hyper-­ No increase in late toxicity
trial fractionation with a HR 0.81, P = 0.05 with hyper-fractionation
MARCH Meta-­ 6515 8% absolute survival benefit at 5 years –
meta-analysis analysis with hyper-fractionated radiotherapy
schedule

Table 30.3 Summary of selected trials in head and neck on accelerated fractionation
Number
Nature of trial of patients Outcome Toxicity
MARCH Meta-analysis 6515 Absolute survival benefit at 5 years –
meta-analysis  • Accelerated radiotherapy [ART]
without total dose reduction—2%
 • ART with dose reduction—1.7%
DAHANCA Randomized 1485 Disease-specific survival—73 vs 66% Higher acute radiation in
6&7 controlled trial favoring accelerated arm the accelerated
[RCT] Overall survival same radiotherapy [53 vs
33%]
Late toxicity—similar
IAEA-ACC RCT 458 5 year overall survival 35% vs 28% Higher acute radiation in
study favoring accelerated arm the accelerated
radiotherapy
Late toxicity—similar
ARTSCAN RCT 750 No significant benefit in overall Higher acute radiation in
study survival or locoregional control the accelerated
between accelerated and conventional radiotherapy
schedules

lag of 4 weeks and during this phase the resis- • Pure accelerated fractionation regimens—
tant tumor clonogens start accelerated repopu- pure accelerated regimens aim to reduce the
lation. An incremental dose of 0.6 Gy/day is overall treatment time without changes in the
required to counter the accelerated repopula- fraction size or total dose. Commonly used
tion to achieve good tumor control. In acceler- strategy includes treating 6 days in a week. It
ated fractionation schedule an attempt to has shown maximum benefit in head and neck
complete radiotherapy before the onset of cancers. Increased acute toxicity is however a
accelerated repopulation is tried. major concern. Some of the trails that evalu-
The various accelerated fraction schedules ated accelerated fractionation and its results
used clinically are are summarized in Table 30.3.
30 Altered Fractionation Radiotherapy 187

• Hybrid accelerated fractionation schedules 30.3 Hypo-Fractionation

alter the fraction size, total radiation dose,
and time distribution in addition to reducing • Hypo-fractionated schedule of fractionation
the overall treatment time. The commonly uses a higher dose per fraction and is best
used hybrid accelerated fractionation sched- suited for tumors with low alfa/beta like breast
ules are and prostate cancer [3]. Tumors with low α/β
–– Type A—overall treatment time is much ratio have shown better local control to hypo-­
shortened with a reduction in the total dose. fractionated radiation.
The prototype for type A is continuous • The rationale behind hypo-fractionation in
hyper fractionated accelerated radiother- palliative setting is delivery of higher biologi-
apy (CHART) cally equivalent doses at shorter treatment
–– Type B—duration of treatment is more duration, but at the risk of higher late normal
modestly shortened, but the total dose is tissue toxicity
kept in the same range. Makes use of twice • The dose per fraction and fractions varies with
daily fractionation. E.g. EORTC 22851 the tumor treated and schedule.
trial. Split-course accelerated radiotherapy • Trials on melanoma, carcinoma prostate, and
was previously used but is inferior due to whole breast radiation—established hypo-­
the gap and must not be practiced fractionated schedule as a standard in these
–– Type C—duration of treatment is more tumors
modestly shortened than type B. Total dose • With development of modern radiation deliv-
is kept same. Makes use of concomitant ery technique this approach has been extended
boost approach. One of the most widely to laryngeal lung cancers and glioblastoma,
used approach. Logistically easier with showing promising results
intensity modulated radiotherapy. • It is also used in the palliative setting where
long term toxicity is of lesser concern.
Continuous, hyper-fractionated, accelerated • This reduces the number of fractions [e.g.,
radiotherapy [CHART]: Pioneered by Mount in breast from 25 to 15] and is of economi-
Vernon Hospital in UK, the CHART schedule cal benefit also. This approach is also suited
delivers a dose of 54 Gy in 36 fractions (1.5 Gy in areas where there is high burden of
per fraction thrice daily at 6 h intervals) over patients on machines especially in devel-
12 days. The schedule aims to improve tumor oped countries.
control by reducing the overall treatment time and • Summary of important trails that evaluated
reduce late effects by using lower dose per frac- role of hypo-fractionation is summarized in
tion. The trial schedule showed very good local Table 30.4.
control and tolerable acute toxicity [occurred after
completion of treatment], but logistic issues and
increased spinal cord toxicity are of concern.
 188

Table 30.4 Summary of trials using hypo-fractionation

Number of
Subsite Author/year Nature of trial patients Fraction size Local control Toxicity
Larynx Sung Phase III randomized trial— 156 2.2 Gy per 5-year local progression-free survival was 77.8%— No difference in toxicity
et al./2013 T1–2 glottic cancer fraction conventional fractionation arm 88.5%—hypo-­ compared to conventional
fractionation arm arm
Breast START A Phase III—early breast 2236 3.2 Gy or Similar local control Similar late adverse effect
trial cancer 3.0 Gy per
fraction
START B Phase III—early breast 1105 2.67 Gy per Similar local control to 50 Gy/25fractions Similar late adverse effect
trial cancer fraction
Prostate HYPRO Phase III—intermediate-risk 820 3.4 Gy per Not superior to conventional radiotherapy with Similar acute genitourinary
trial to high-risk prostate cancer fraction respect to 5-year relapse-free survival and gastrointestinal toxicity
S. Mallick and G. K. Rath
30 Altered Fractionation Radiotherapy 189

References domised trials and 17,346 patients. Radiother Oncol.

2009;92(1):4–14.
3. Haviland JS, Owen JR, Dewar JA, Agrawal
1. Mallick S, Benson R, Julka PK, Rath GK. Altered
RK, Barrett J, Barrett-Lee PJ, et al. The UK
fractionation radiotherapy in head and neck squa-
Standardisation of Breast Radiotherapy (START)
mous cell carcinoma. J Egypt Natl Canc Inst.
trials of radiotherapy hypofractionation for treat-
2016;28(2):73–80.
ment of early breast cancer: 10-year follow-up
2. Pignon JP, le Maître A, Maillard E, Bourhis J,
results of two randomised controlled trials. Lancet
et al. Meta-analysis of chemotherapy in head and
Oncol. 2013;14(11):1086–94.
neck cancer (MACH-NC): an update on 93 ran-
 Therapeutic Index and Its Clinical
Significance 31
Rony Benson and Supriya Mallick

• The main purpose of delivering radiotherapy is

100%
to cure the disease with no or minimal normal
Tumor control/Complications Probablity
tissue complications. An ideal radiotherapy plan
should have a 100% chance of curing the dis-
ease while there is 0% chance of normal tissue Probablity of
Tumor Control Probablity of
50%

complications which never occur. But in reality Complications

normal tissues undergo significant dammage by

the dose required to control the tumor; while the
tumor may not receive an adequate dose if the
100% normal tissue protection is planned.
0%

• When we plot a graph of probability of tumor Increasing Radiation Dose----->

control in Y axis against radiation dose in X Fig. 31.1 Diagram showing concept of therapeutic index
axis what we get is the tumor control probabil-
ity (TCP). Similarly when probability of nor-
mal tissue complications in Y axis is plotted with radioresistant tumors have a narrow ther-
against radiation dose in X axis we get the apeutic index (Fig. 31.2).
normal tissue complication probability • The therapeutic index for a particular tumor
(NTCP) [1]. TCP and NTCP curves are sig- may also depend on the location of tumor,
moid in shape. The therapeutic index (TI) e.g., a soft tissue sarcoma of the extremity
defines how the TCP relates to NTCP for dif- may have a good therapeutic index, while a
ferent doses of radiation (Fig. 31.1). retroperitoneal sarcoma located near to kid-
• TI = NTCP/TCP neys will have a very unfavorable therapeutic
• Usually radiosensitive tumors like seminoma index.
have a wide therapeutic index, while those • Dose volume histograms created in conformal
radiotherapy plans and TCP and will help cli-
nicians during treatment planning.
• An ideal radiotherapy plan where there is
R. Benson (*) 100% chance of tumor control and 0% chance
Department of Medical Oncology, RCC, of normal tissue toxicity never really exists in
Thiruvananthapuram, Kerala, India
real world scenario. Achieving an optimal bal-
S. Mallick ance between TCP and NTCP is a basic aim of
Department of Radiation Oncology, National Cancer
any radiotherapy plan. This can be achieved
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 191

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_31
192 R. Benson and S. Mallick

100%

100%
Tumor control/Complications Probablity

Tumor control/Complications Probablity

Probablity of
Tumor Control

Probablity of Probablity of
Tumor Control
50%

50%
Complications
Probablity of
Complications
0%

0%
Increasing Radiation Dose-----> Increasing Radiation Dose----->
Tumor With high Radiosensitivity like Seminoma showing good therapeutic index Tumor With less radiosensitivity like chordoma showing narrow therapeutic index

Fig. 31.2 Therapeutic index for radiosensitive and radioresistant tumors

by altering the radiation fractionation or radia- overcoming hypoxia. This can be achieved
tion sensitizers or radiation protectors. either by use of agents like nimorazole which
is a hypoxic cell sensitizer or by administra-
tion of agents that are preferentially cytotoxic
31.1 Modifying Therapeutic Index to hypoxic tumor cells (e.g., hyperthermia).
for Clinical Advantage This leads to shifting of TCP curves to the left,
thereby improving therapeutic index.
Modifying therapeutic index is the main advan- 5. Radio Protectors—The radio protectors
tage of adding chemotherapy or radiation sensi- (e.g., Amifostine) mainly act by neutraliz-
tizers or radio protectors. ing free radicals generated by ionizing
radiations in the normal tissue, thereby
1. Hyperfractionation—In hyperfractionation reducing normal tissue complication rates
small dose per fraction with two or three frac- [3]. Thus this leads to shifting of NTCP
tion delivered per day is used to achieve a curves to the right, thereby improving ther-
higher biologically effective dose to the tumor. apeutic index.
Using the lower dose per fraction also reduces 6. Extracorporeal radiotherapy where tumor tis-
the chances of long term normal tissue com- sue is removed and the bone is irradiated out-
plications (shifting the NTCP to right), side the body may be one of the radiotherapy
thereby improving the therapeutic index. plans where we may archive something near
2. The therapeutic index is improved by reduc- to an ideal therapeutic index.
ing the size of the target volume and the mar-
gins by using image guidance in radiotherapy
planning [2]. References
3. Concurrent Chemotherapy—The use of con-
current chemotherapy acts as a radiosensitizer 1. Chargari C, Magne N, Guy JB, Rancoule C, Levy A,
Goodman KA, et al. Optimize and refine therapeu-
and thereby shifts the TCP to left, thus improv-
tic index in radiation therapy: overview of a century.
ing therapeutic ratio. The nonoverlapping tox- Cancer Treat Rev. 2016;45:58–67.
icity with concurrent chemotherapy (some 2. Beasley M, Driver D, Dobbs HJ. Complications of
overlapping toxicity exists like mucositis with radiotherapy: improving the therapeutic index. Cancer
Imaging. 2005;5:78–84.
concurrent cisplatin) does not greatly alter the
3. Montay-Gruel P, Meziani L, Yakkala C, Vozenin
NTCP. MC. Expanding the therapeutic index of radiation
4. Radiation Sensitizers—The use of radiosensi- therapy by normal tissue protection. Br J Radiol.
tizers helps in optimizing therapeutic index by 2018:20180008. https://doi.org/10.1259/bjr.20180008.
 Part V
Clinical Cases
 Carcinoma Cervix
32
Rony Benson, Supriya Mallick, and Goura K. Rath

32.1 History Taking 32.3 Examination

• Bleeding PV • Start with inspection of external genitalia—

• Discharge P/V (foul smelling)—necrotic labia majora and minora, mons
growth • Per speculum
• Swelling in the groin –– Vagina
• Back pain—involvement of uterosacral liga- –– Urethral mass
ment, vertebral mets –– Mass/ulcer if seen—explain in detail (size,
• Pain in the abdomen—PA-LN mets, margins, location, discharge/bleeding)
hydroureteronephrosis • P/V—empty bladder in lithotomy position, do
• Urinary symptoms—bladder infiltration a bidigital and bimanual palpation
• Bleeding PR—rectal infiltration –– Uterus-anteverted/retroverted—important
during ICRT application
–– Cervical growth—in detail
32.2 Other Relevant History –– Vagina
–– Fornices
• History of other STDs • P/R—bimanual
• Multiple sexual partners—HPV –– Anal tone, rectal mucosa
• Early first intercourse, high parity –– Parametrium—thickening, nodularity, lat-
• Smoking eral extent, and fixity to lateral pelvic wall
• Examination of inguinal area—LN
• Abdominal examination—rarely hepatomeg-
aly or PA-LN
R. Benson (*) • Respiratory, CVS and CNS examination
Department of Medical Oncology, RCC, • Do a breast examination also
Thiruvananthapuram, India
S. Mallick
Department of Radiation Oncology, National Cancer 32.4 Differential Diagnosis
Institute-India (NCI-India), Jhajjar, Haryana, India
G. K. Rath • Ca cervix
Dr. B.R. Ambedkar Institute-Rotary Cancer Hospital, • Ca endometrium
All India Institute of Medical Sciences,
New Delhi, India • Cervical polyp—mass with bleeding

© Springer Nature Singapore Pte Ltd. 2020 195

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_32
196 R. Benson et al.

• TB—especially when patient presents with Risk of Lymph node involvement as per stage
discharge STAGE PELVIC LN PARA A-LN
• PID—especially when patient presents with 1A1 0.5 0
discharge 1A2 5 <1
1B 15 2.2
IIA 25 11
IIB 30 20
32.5 Work-Up
III 45 20
IV 55 40
• Complete blood counts, RFT, LFT
• Examination under anaesthesia and punch biopsy Fig. 32.1 Incidence of nodal involvement with stage
• CECT abdomen and pelvis (or MRI pelvis)
from stage IB
• HIV testing if at risk 32.8 Prevention and Screening
• Cystoscopy and sigmoidoscopy—from stage IB2
• Pap smear is done for only patients with nor-
mal appearing cervix, those with visible lesion
32.6 Staging: FIGO—Clinical should be biopsied
Staging FIGO 2018 • Screening should begin approximately 3 years
after a woman begins to have sexual inter-
IA—microscopic d/s disease limited to cervix course, but no later than 21 years old by 3
<5 mm stromal invasion yearly pap smear
• >30 years—cytology + HPV testing may be
• A1—<3 mm stromal invasion done every 5 years
• A2—≥3 to 5 mm stromal invasion • >65 years—screening not required
• Pap smear not very good for screening
IB—disease limited to cervix with deepest adenocarcinoma
invasion ≥5 mm • Liquid-based cytology—more sensitive, and
allows a faster turnaround time
• B1—>5 mm stromal invasion and less than • To be effective, vaccination needs to be given
<2 cm size in adolescence (age recommended is
• B2—≥2 cm and <4 cm in greatest dimension 9–26 years, 3 doses)
• B3—≥4 cm • Bivalent vaccine—against HPV 16 and 18—
PATRICIA trial
IIA—extension to upper 2/3 of vagina • Quadrivalent—activity against HPV 6, 11, 16, and
(IIA1 < 4 cm, IIA2 ≥ 4 cm) 18–90% efficacy—FUTURE-I, FUTURE-­II trials
IIB—extension to parametrium but not to pelvic wall • Nine-valent—in addition covers HPV 31, 33,
IIIA—extension to lower 1/3 of vagina 45, 52, and 58
IIIB—extension to pelvic wall/hydronephro- • Vaccination does not obviate the need for
sis/nonfunctional kidney screening as there are other virus types that
IIIC—pelvis (C1) or paraaortic LN (C2) cause cervical cancer
IVA—bowel/bladder involvement
IVB—metastatic disease
32.9 Treatment Outline

• CA in situ/IA-Conisation/LEEP/trachelec-
32.7 Nodal Involvement tomy (1A2)/SH
with Stage • 1A1—brachy alone is also an option
• 1A2—RH is general recommendation (LN
Incidence of pelvic and paraaortic nodes with dissection is usually recommended)
clinical stage is summarised in Fig. 32.1. • IB-IIA—surgery preferred (adjuvant RT/
32 Carcinoma Cervix 197

CTRT as per indicated) Table 32.1 Treatment options in carcinoma cervix

• 1B2, IIA2—CTRT may be preferred over sur- Surgery in early carcinoma RT in early carcinoma
gery [1] cervix cervix
• IIB-IVA—CTRT Surgery is preferred for Easier to deliver for
young women as radical patients who are obese/
• IV—Pall RT±chemo
hysterectomy and pelvic elderly or have severe
• Adjuvant RT (Sedlis criteria)—>4 cm, deep lymphadenectomy illness—major C/I to
cervical stromal invasion, only simple Advantages of possible the surgical approach
hysterectomy, LVSI, closemargin-3 mm (to
­ ovarian conservation and Avoids the risks of
preservation of sexual anaesthesia and the
the middle or one-third depth)-PFS benefit [2]
function laparotomy scar
• Adjuvant CTRT-LN, parametrium, margin Shortening and fibrosis of Iatrogenic mortality is
positivity—overall survival benefit the vagina can be limited if rare
• Concurrent cisplatin from 1B2 treated radi- the woman is sexually Complications after
active radiotherapy arise later
cally [3]
Pelvic relapses can be than after surgery,
successfully cured by although radiotherapy-­
radiotherapy related complications
32.10 Surgery Surgery allows the status of are often permanent
the lymph nodes, the most
dependent variable
• In surgically treated patients—premenopausal associated with survival, to
patients may preserve ovaries. Postmenopausal be assessed accurately
patients should also have a BSO Radiotherapy-induced
• LN dissection is usually recommended from menopause
Vaginal stenosis
1A2 onwards Late complication of
• More preferred over RT if multiple uterine radiation-induced
fibroids are present carcinogenesis
• Table 32.1 summarises various treatment Other—cystitis and
proctitis
options in carcinoma cervix

generally accepted. A comparison of 2D vs 3D

32.11 Radiotherapy planning is summarised in Fig. 32.3.

32.11.1 EBRT Planning

32.11.2 Conformal Radiotherapy
2D Planning—4 field technique borders
(Fig. 32.2) • MRI fusion preferable to aid in delineation,
GTV as per MRI and clinical examination
• Superior border—between L4 and L5 vertebrae findings
• Inferior border—2 cm below the lower extent • Bladder and rectal protocol to be adhered to
of the clinical tumour or the inferior edge of • CTV-T includes the primary GTV-T with
obturator foramina potential microscopic spread to cervix, uterus,
• Lateral borders—1.5–2 cm outside the bony parametrial tissues, upper vagina, and broad
pelvic side wall and proximal utero-sacral ligaments
• Posterior border—lower border of S2 • CTV-N includes obturator, internal, exter-
vertebra nal, and common iliac and upper presacral
• Anterior border—through the symphysis nodes
pubis • CTV to PTV margin of 10–20 mm

Lateral beams are usually used to spare the Figure 32.4 shows conformal radiotherapy
rectum with decreased weighting of the posterior plan for carcinoma cervix.
beam. Doses of 80–90 Gy for the bladder and The radiation doses for carcinoma cervix are
70–75 Gy for the rectum and sigmoid colon are summarised in Table 32.2.
198 R. Benson et al.

Fig. 32.2 2D planning in carcinoma cervix

2 FIELD 4 FIELD
Less time required for planning Less skin & subcutaneous reaction
more skin reaction More homogenous dose distribution (especially in large
Can treat lower presacral lymph nodes/utero separation)
sacral Lateral most part of parametrium also gets effective dose
Useful when lower part of vagina involved If beam weightage is adjusted the dose to bladder and rectum
May have hour glass contraction can be decreased
Under dose to uterosacral ligaments

Fig. 32.3 Comparison of 2 field and 4 field technique in carcinoma cervix

Fig. 32.4 Contouring CTV for conformal planning in carcinoma cervix

32.11.3 B
 rachytherapy (More Details point is 5 mm behind the posterior vaginal
in Brachytherapy Cervix wall at the level of the lower end of the intra-
Chapter) uterine source.
• Doses of >87 Gy to the HR CTV have been
• The dose is prescribed to Manchester point A, associated with improved local control.
defined as 2 cm above the lateral vaginal for- • If image-guided HRCTV includes cervix
nices and 2 cm lateral to the central uterine and any residual disease or T2 grey areas
tube. in MRI.
• The ICRU bladder point is the posterior sur- • Doses for 2 mL of tissue volume (D2cc) for
face of the bladder balloon, and the rectal the OAR are calculated at 2 Gy per fraction.
32 Carcinoma Cervix 199

Table 32.2 Radiation options and doses in carcinoma between the ovoids.
cervix • Packing is done with 40% iodinated contrast
Radiotherapy dose to identify on radiographs.
CIN/IA1 Stage IB2 and IIA Stage IIB or • HDR to LDR conversion factor—0.56–0.6.
above
Brachy EBRT 45 Gy in 25 EBRT 50.4 Gy in
alone daily fractions of 28 daily fractions
1.8 Gy given in of 1.8 Gy given 32.11.4 Palliative RT
5 weeks followed in 5.5 weeks
by followed by • 20 Gy in 5 fractions or 30 Gy in 10 Fractions
The dose is prescribed to the 100%
isodose using 6–10 MV photons
LDR Intracavitary Intracavitary
equivalent brachytherapy brachytherapy 32.11.5 Chemotherapy
65–75 Gy 14 Gy in 2 21 Gy in 3
HDR— fractions given in fractions over • Concurrent weekly cisplatin 40 mg/m2 is
7∗5/7∗6 5–8 days to point A 5–8 days to
(35–42 Gy) point A
given for both high risk early stage disease
EBRT boost to central tumour when and locally advanced tumours unless patient is
brachytherapy not feasible (OR if medically unfit.
perforation) 15 Gy in 8 daily • Concurrent cisplatin around 10% survival
fractions/20 Gy in 11 daily fractions
advantage compared to radiation alone—
Adjuvant
greater benefit in patients in earlier stages
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks
50.4 Gy in 28 daily fractions of 1.8 Gy in 51/2 weeks (IB2 and IIB).
if macroscopic residual disease • Concurrent carboplatin or non-platinum
Followed by HDR—6–8 Gy at 0.5 cm from surface of chemoradiation regimens are options for
applicator in 2 fractions patients who may not tolerate cisplatin-­
containing schedules.
Iso-equivalent doses of 80–90 Gy for the blad- • Radio-equivalence of adding cisplatin =
der and 70–75 Gy for the rectum and sigmoid 10 Gy.
colon are generally accepted. • Pall chemo—Final analysis from the GOG-­
• Overall treatment time should not exceed 0240 trial found that bevacizumab in combi-
56 days including brachytherapy nation with cisplatin paclitaxel is associated
(ideally < 49 days). with a significantly improved overall survival
• Ideal brachytherapy application (16.6 months versus 13.3 months) versus che-
–– Tandem—1/3 of the way between S1 and motherapy alone and is the standard palliative
S2 and the symphysis pubis. chemotherapy regimen.
–– The tandem-midway between the bladder • Platinum paclitaxel or single agent platinum
and S1–S2. or paclitaxel may be also used as clinical sce-
–– Marker seeds should be placed in the nario or financial aspects permit.
cervix.
–– Tandem should bisect the ovoids.
–– The bladder and rectum should be packed 32.11.6 Follow-Up
away from the implant.
–– The ovoids should fill the vaginal forni- • Every 3 monthly ∗2 years, then 6 monthly ∗5
ces—largest ovoid size to be used. years, then annually
–– The ovoids should be separated by 0.5– • Annual Pap smear
1.0 cm, admitting the flange on the • Imaging not routinely recommended
tandem. • Dilation to prevent stenosis started 2–4 weeks
–– The axis of the tandem should be central after radiotherapy
200 R. Benson et al.

32.11.7 Survival Stage Wise References

• IA: 95–100% 1. Landoni F, Maneo A, Colombo A, Placa F, Milani R,

Perego P, et al. Randomised study of radical surgery
• IB1: 85–90%
versus radiotherapy for stage Ib-IIa cervical cancer.
• IB2: 60–70% Lancet. 1997;350(9077):535–40.
• IIA: 75% 2. Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz
• IIB: 60–65% SS, Muderspach LI, et al. A phase III randomized trial
of postoperative pelvic irradiation in Stage IB cervical
• IIIA: 25–50%
carcinoma with poor prognostic features: follow-up
• IIIB: 25–50% of a gynecologic oncology group study. Int J Radiat
• IVA: 15–30% Oncol Biol Phys. 2006;65(1):169–76.
• IVB: <10% 3. Lukka H, Hirte H, Fyles A, Thomas G, Elit L,
Johnston M, et al. Concurrent cisplatin-based che-
motherapy plus radiotherapy for cervical can-
cer—a meta-­analysis. Clin Oncol (R Coll Radiol).
32.11.8 Recurrence 2002;14(3):203–12.

• Recurrence postsurgery—RT
• Recurrence post-RT—surgery/can try reirra-
diation if >1 year
 Case Carcinoma Breast
33
Rony Benson, Supriya Mallick, and Goura K. Rath

33.1 History Taking 33.2 Other Relevant History

• Breast—lump [fibroadenoma common • Diabetes/hypertension—diabetes is associ-

< 35 years] ated with liver, pancreas, endometrium, colon
• Discharge/bleeding and rectum, breast, bladder cancer
–– Blood—carcinoma, duct papilloma • Age of menarche, no of children [more in
–– Pus—abscess nulliparous]
–– Milk—galactocele • Breast feeding and duration
• Skin/nipple changes—recent retraction of • OCP use—increases risk of breast, cervix can-
nipple cers, but reduces the risk of ovarian, endome-
• Cyclical pain in fibroadenosis [more aggra- trial, colon cancers
vated by cyclic changes in hormones] • Hormone replacement therapy (HRT) use—
• Loss of weight combined HRT use is more risky than estrogen
• Swelling in the axilla only HRT. Risk increases with duration of HRT
• Symptoms of metastasis—liver, lung, bone, • Smoking—higher risk of breast cancer in
brain younger, premenopausal women
• Gynecological symptoms—bleeding [endo- • Family history of breast/gynecological can-
metrial cancer]—common age and common cers—draw a pedigree chart
risk factors • A comparison of BRCA 1 and 2 is summa-
rized in Table 33.1

33.3 Examination
R. Benson (*)
Department of Medical Oncology, RCC, • Obesity—BMI increased risk of breast cancer
Thiruvananthapuram, Kerala, India
S. Mallick Examination of breast—patient must be
Department of Radiation Oncology, National Cancer stripped to waist
Institute-India (NCI-India), Jhajjar, Haryana, India
G. K. Rath Inspection Always compare with normal side
Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, [arms by side/arms elevated [lump more visible
All India Institute of Medical Sciences, as well as axilla]/bending forward]
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 201

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_33
202 R. Benson et al.

Table 33.1 Comparison of BRCA 1 and 2

BRCA 1 BRCA 2
Gene 17q21 13q
Incidence 2% of breast cancers 1%
Risk breast cancer 40–85% lifetime risk of breast 25–65% lifetime risk of breast cancer
Risk ovarian 25–65% lifetime risk of ovarian 10–15% lifetime risk of ovarian
cancer
Type of cancer ER-, PR-, and HER2-negative, often ER+
with a basal-like phenotype Can occur in males
BRCA2 tumors typically express ER and PR and
tend to be of higher grade with less tubule
formation

1. Compare the 2 sides first—any swelling/skin Each quadrant must be palpated systemati-
changes cally, then nipple and axillary tail
2. Nipple
• Position [nipple will be pulled towards 1. Local rise of temperature/tenderness—com-
lump in carcinoma while in fibro ade- pare with opposite side
noma it will be pushed away], measure 2. Mass site [quadrant/site as in clock], size,
length of level of nipple from clavicle and surface, margin [first with flat hand then
midline between fingers]
• Look for retraction of nipple [recent or not 3. Consistency
pulled towards tumor] 4. Fixity to skin—any tethering/dimpling on
• Look for erosion—Paget's moving skin [dimpling is due to involvement
• Discharge [blood—carcinoma/papilloma, of Cooper's ligament]
black—duct papilloma, milky—galacto- 5. Fixity to pectoralis major—place arm over
cele, purulent] hip firmly [first check with normal position
3. Areola—cracks/eczema/ulcers— [involved in and then look for restricted mobility by plac-
Paget's] ing arm over hip firmly]. Must look for
4. Breast—position, size and shape, puckering, mobility in plane parallel and perpendicular
swelling to muscle
5. Skin over breast 6. Fixity to serratus anterior—check tumors of
• Color[red]/Peau d’orange the outer lower quadrant [by pushing against
• Enlarged veins—phyllodes tumor the wall and checking mobility in vertical
• Retraction-blockage of sub-cuticular and transverse position]
lymphatics 7. Fixity to chest wall
• Puckering 8. Palpation of nipple—periphery to nipple and
• Nodules then behind nipple to look for any tumors
• Ulcer deep to nipple and any discharge
6. Arm and thorax—for nodules, edema [axil- 9. Palpation of axilla
lary lymphatic obliteration], thrombosis in • Pectoral group—using right hand of the
veins examiner for left side axilla of the patient
7. Axilla, SCF—for nodes • Central and apical
• Brachial group—using left hand for left
Palpation side
Sitting position—arms by side/arms in hip/ • Subscapular—along post axillary fold,
supine from behind
Palpate the normal breast first—with palmar 10. Infraclavicular, supraclavicular fossa and
surface of fingers neck for any nodes
33 Case Carcinoma Breast 203

Examination of the abdomen 33.5 Work Up

• Hepatomegaly, free fluid
• Complete blood count, Renal function test and
Examination of the respiratory system Liver Function test
• Biopsy—Trucut biopsy preferred over FNAC
• Pleural effusion/consolidation as it can differentiate DCIS from carcinoma
Examination of the skeletal system—for bony and in assessing ER/PR/Her2 status [triple
tenderness assessment includes a complete history, triple
Examination of CNS—headache, diplopia, assessment is performed including: physical
seizure examination, radiological investigation, and
PV Examination needle biopsy]
• FNAC of suspicious axillary LN
• Krukenberg deposits • B/L mammogram with USG—look for multi-­
• Uterine/ovary—malignancies focality, look for contralateral breast cancer
• MRI if axillary lymphadenopathy with
unknown primary malignancy, in patients
33.4 Differential Diagnosis
with breast implant and for assessment post
for Carcinoma Breast
neoadjuvant chemotherapy.
• T1 and T2 primary breast tumors <2% inci-
• Phyllodes tumor—Large tumor, dilated veins,
dence of metastatic disease, so routine staging
less LN
of asymptomatic patients for metastases is not
• Fibro adenosis—30–40 years, painful, bilat-
indicated in T1 and T2 cancers
eral lesion with pain showing cyclical varia-
• CECT chest abdomen pelvis and bone scan in
tion with menstrual cycles
T3/N1 [in nearly stage disease done if altered
• Fibro adenoma [breast mouse]—30–40 years
LFT, high ALP or if symptomatic]
as mobile, rubbery, round movable swelling
• PET may be done instead of CECT chest-­
• Fat necrosis—associated trauma, ecchymosis
abdomen-­pelvis and bone scan
over the skin
• Abscess—non-lactating breast, fever, rapid
onset of symptoms
• Mastitis—in lactating breast, occurs within 33.6 Staging
3 m of delivery
• Duct papilloma—no mass with bloody • The AJCC staging and stage grouping are tab-
discharge ulated in Tables 33.2 and 33.3

Table 33.2 AJCC 2017 staging for carcinoma breast

T1: tumor ≤2.0 cm in greatest dimension Clinical N
 • T1mi—<1 mm N1: Mobile ipsilateral axillary LN
 • T1a: tumor >0.1 cm–≤0.5 cm N2a: I/L axillary lymph nodes fixed/matted
 • T1b: tumor >0.5 cm–≤1.0 cm N2b: ipsilateral internal mammary nodes in the absence of
 • T1c: tumor >1.0 cm–≤2.0 cm axillary lymph node
T2: tumor >2.0 cm–≤5.0 cm N3a: I/L infraclavicular
T3: tumor >5.0 cm N3b: ipsilateral internal mammary lymph node(s) and axillary
T4a: extension to chest wall, not including lymph node(s)
pectoralis muscle N3c: metastasis in ipsilateral SCF
T4b: edema (including Peau D’orange) or Pathological N
ulceration of the skin of the breast, or satellite pN1a: 1–3 axillary lymph nodes
skin nodules confined to the same breast pN2A: metastasis in 4–9 axillary lymph nodes
T4c: both T4a and T4b pN3A: metastasis in ≥10 axillary lymph nodes
T4d: inflammatory carcinoma
204 R. Benson et al.

Table 33.3 AJCC stage grouping for carcinoma breast 33.8 Treatment Outline
AJCC stage Group
I I Early Breast T1 Early Breast Cancer [EBC]
II IIA Cancer T2/N1 • Breast conservation surgery (BCS)/modified
IIB T2+N1/T3 radical mastectomy (MRM) + sentinel lymph
III IIIA LABC T3+N1/N2
node biopsy (SLNB) [in node negative] fol-
IIIB T4
lowed by adjuvant radiotherapy (RT) ± che-
IIIC N3
IV IV Metastatic M
motherapy ± hormone therapy ± anti-Her2neu
therapy
–– Adjuvant chemotherapy risk predictors—
33.7 Screening adjuvant online, PREDICT
–– Adjuvant chemotherapy genomic scor-
• US preventive services task force recom- ing—oncotype-DX (18 gene signature),
mends screening for women aged 50–74 with prosigna, endopredict, mammaprint (70
biennial screening mammography gene signature)
• American Cancer Society recommends yearly
mammograms for women aged 50–54 years Locally Advanced Breast Cancer [LABC]
and biennial screening mammography for • NACT ± anti Her2neu therapy followed by
women aged >55 years surgery [BCS/MRM] followed by RT ± hor-
mone therapy ± anti Her2neu therapy
Prevention approaches [1]: • MRM followed by RT ± chemotherapy ± hor-
mone therapy ± anti Her2neu therapy
1. Risk assessment most commonly is done by
GAIL method (limitation: overestimation of Metastatic Breast Cancer [MBC]
risk in non-Caucasian women). • In oligometastatic disease treatment should
2. In GAIL criteria the following criteria is con- follow the protocol of LABC
sidered “menarche, age at first live birth, • Remaining patients: Options are
patient’s current age, number of first-degree –– Surgery: toilet mastectomy
relatives with IBC, race/ethnicity, number of –– Radiation: palliation for bone, brain
prior breast biopsies, and the results of these metastasis
biopsies”. –– Systemic therapy:
3. Eligible patients: any woman more than ER positive and Her2/neu negative and
35 years with a GAIL model prediction risk not in visceral crisis hormonal therapy
for breast cancer of at least 1.66% at 5 years should be considered standard
4. Agents: In premenopausal—tamoxifen 20 mg ER positive and Her2/neu positive and
for 5 years; and post-menopausal—either ral- not in visceral crisis hormonal therapy
oxifene or exemestane can be used. with anti-her2/neu therapy should be
5. It reduces only chances of hormone sensitive considered standard
breast cancer. ER negative and Her2/neu positive and
6. Other different agents are being evaluated for not in visceral crisis chemotherapy with
reducing the risk of hormone non-sensitive anti-her2/neu therapy should be consid-
breast cancer (viz., fenretinide, metformin, ered standard
statins, tibolone, etc.). ER negative and Her2/neu negative OR
7. For BRCA mutated women, bilateral mastec- patient in visceral crisis chemotherapy
tomy and salpingo-oophorectomy is advised. should be considered standard
33 Case Carcinoma Breast 205

33.9 Surgery • Radiotherapy Dose

–– Conventional fractionation: 50 Gy/25 frac-
• Breast conservation surgery should be offered tions followed by a boost of 10–16 Gy
to all eligible patients –– Hypofractionation: 40 Gy/15 fractions
• Absolute contra indications for BCS are mul- (boost is not mandatory) [START A,
tifocal breast cancer, previous irradiation of START B, Canadian trial] [3]
the breast, persistent positive tissue margins –– Extreme hypofractionation:
after surgery, and other contraindication for Once in a week dose: 28 Gy in 5 fractions
radiotherapy or 30 Gy in 5 fractions [UK FAST trial]
• SLNBx should be done in all early stage breast Continuous in a week dose: 26 Gy in 5
cancer patients with negative LN. Done by fractions or 27 Gy in 5 fractions [UK
injecting blue dye and a radioactive colloid FAST FORWARD trial]
tracer around the tumor (peritumoral), into the • Indication of adjuvant RT after NACT: No
dermis (subdermal) or under the nipple randomized evidence
(subareolar) –– Patients with Stage III B/Stage IIIC disease
• In SLNB if 1–2 nodes are positive further (>5 cm tumor and cN+), or residual disease
ALND may be omitted but patients must after NACT (<pCR)
receive whole breast radiation by tangential • Omission of Rt in elderly: PRIME II and
field CALGB trial reported significantly higher
• SLNB in node positive patients after NACT is local recurrence after omission of RT even in
being evaluated. In such cases prior a­ ssessment the most favorable patients (Age 70 years,
with axillary USG and placement of clip is Stage I (T1N0M0), ER+)
recommended • RT in TNBC: No randomized data
• Disease-free margins of at least 1 mm are –– Radiotherapy significantly lower risk of
acceptable locoregional recurrence irrespective of the
type of surgery
–– Radiotherapy not consistently associated
33.10 Radiotherapy with OS
–– Benefits may be obtained in women with
• All patients of BCS should receive adjuvant late-stage disease and younger patients
radiation • Internal mammary radiation: IMN radiation
• A boost dose of 10–16 Gy resulted in a greater along with chest wall and SCF was found to
reduction of local failure in patients younger impart disease free survival benefit. However,
than 50 years the true benefit from IMN radiation could not
• Boost irradiation leads to a 50% risk reduction be assessed in these trials. Risk of cardiac side
in patients with age <50 years, grade 3 tumor, effects also may increase. Hence only in
and vascular invasion [2] patients with disease in inner quadrant should
• Adjuvant chest wall RT is recommended for be considered eligible.
patients with T3–T4, ≥4 positive lymph
nodes, and excision margin <1 mm
• Patients with 1–3 positive lymph nodes may 33.11 EBRT 2D Planning
also benefit from chest wall RT and SCF RT
especially in patients with grade 3, T2 disease • Most commonly the patient is treated supine
or presence of LVE with a breast board
• Adjuvant radiotherapy—reduces the inci- • Prone position may be helpful in patients with
dence of locoregional recurrence from 30% to pendulous breasts
10% at 20 years and breast cancer deaths by • Use of respiratory motion management is fur-
5% at 20 years ther beneficial
206 R. Benson et al.

Table 33.4 Field borders for 2D planning in carcinoma

breast
Field borders
Chest wall/ SCF SCF and
whole breast axilla
Medial Midline 1 cm 1 cm
meaxial to meaxial to
midline midline
Lateral Mid axillary Outer border Lateral
line of 1st rib or border of
medial most humeral
surgical clip head
Superior Suprasternal C7/T1, C7/T1, Fig. 33.2 Contouring CTV for conformal planning in
notch covering covering carcinoma breast
SCF fossa SCF fossa
Inferior 1–2 cm, Superior Superior
• CTV for SCF includes SCF and level 3 axil-
below breast border of border of
tissue chest wall chest wall lary lymph nodes
field field • CTV for axillary lymph node includes levels
1–3 of the axilla and the medial SCF nodes
• Simple, forward-planned, field-in-field IMRT
is the preferred conformal treatment technique
for whole breast radiotherapy and it reduces
the late toxicity and improves cosmetic out-
come following adjuvant RT

33.13 Organ at Risk (OAR)

• 2-D planning-central lung distance [CLD]

should be less than 2 cm and maximum heart
Fig. 33.1 2D planning for carcinoma breast
distance (MHD) must be kept to less than
1 cm
• The anterior border of the field in free air • For 3-D Planning—ipsilateral lung V30%
should be at least 1.5 cm from the skin should be kept ≤17% and V25% of the heart
surface kept ≤5% and V5% of the heart kept ≤30%
• Field borders for 2D planning are summarized
in Table 33.4
• Figure 33.1 shows 2D planning for carcinoma 33.14 Brachytherapy
breast
• Maybe used as boost or as sole treatment in
form of APBI
33.12 Conformal Radiotherapy • Further details are given in chapter on breast
brachytherapy
• The CTV post BCS is the glandular breast tis-
sue. The PTV is the CTV with a 1 cm margin,
usually allowing 5 mm skin-sparing. 33.15 Palliative RT
• The CTV post mastectomy includes the skin
flaps, but not the muscle or the rib cage. Bolus • For bleeding or pain—36 Gy in 6 fractions of
may be used in patients with inflammatory 6 Gy once or twice weekly/20 Gy in 5
tumors, positive skin margins (Fig. 33.2) fractions
33 Case Carcinoma Breast 207

• For bone metastasis—8 Gy single fraction for high risk of disease recurrence (Grade II IDC,
painful bone metastasis; however, 30 Gy in 10 node positive tumor)
fractions may be advised for patients with • In premenopausal ovarian function suppres-
­limited bone metastasis and hormone sensitive sion with exemestane is also an option
tumor

33.19 Palliative Hormone Therapy

33.16 Neoadjuvant/Adjuvant
Chemotherapy • Palliative first line—in patients without vis-
ceral crisis [visceral crisis is defined as severe
• Sequential anthracyclines and taxanes is one organ dysfunction with signs and symptoms,
of the most preferred agents [e.g., ACT → T] laboratory studies, and rapid progression of
• Trastuzumab if indicated may be added with disease]
taxanes and continued for 1 year –– Post-menopausal—CDK inhibitor plus AI/
fulvestrant
–– Premenopausal—ovarian function sup-
33.17 Palliative Chemotherapy pression and AI plus CDK inhibitor/
Tamoxifen
• Sequential single agents preferred over • Primary endocrine resistance is relapsed while
combination on the first 2 years of adjuvant endocrine ther-
• Patients whose tumors are ER positive may be apy or progression within first 6 months of
considered for palliative chemotherapy in first line endocrine therapy
patients with endocrine resistance/visceral • Secondary endocrine resistance is relapsed
crisis after the first 2 years to within 12 months of
• An anthracycline/taxane may be used in first completing adjuvant endocrine therapy, or
line[if it has not been used in the adjuvant progression within after 6 months of first line
setting] endocrine therapy
• Taxane may be used in second line if anthra- • Options in second line—AI if first line tamox-
cycline used in first line and vice versa ifen, exemestane, fulvestrant, exemestane plus
• Capecitabine or vinorelbine may be used in everolimus
third line
• Chemotherapeutic agents like capecitabine,
vinorelbine, and paclitaxel can be continued as 33.20 Anti-Her2u Treatment [in
long as there is a response/unacceptable toxicity Her2 U 3+/FISH Positive]

• The main toxicity of trastuzumab is cardiac

33.18 Adjuvant Hormone Therapy toxicity. Patients should have left ventricular
function assessed before starting trastuzumab
• All hormone sensitive patients should receive and every 3 months during treatment
either tamoxifen for 5 years (premenopausal) • Adjuvant preferred agent—Trastuzumab plus
or aromatase inhibitor (AI) for 5 years chemotherapy [1 year is preferred]
(post-menopausal) • Neoadjuvant preferred agent—trastu-
• Before starting AI patients should be advised zumab ± pertuzumab plus chemotherapy
for DEXA scan and accordingly may be • Metastatic Setting
advised for bisphosphonate and oral calcium –– First line—trastuzumab + pertuzumab +
supplement. taxane
• Extending adjuvant tamoxifen up to 10 years –– Second Line—TDM-1
might be beneficial for selected patients with –– Third Line—lapatinib + capecitabine
208 R. Benson et al.

–– In case of progression on trastuzumab, the 33.25 Male Breast Cancer

combination of trastuzumab + lapatinib is
also a reasonable treatment option in the • Lobular carcinoma does not occur in males
course of the disease • Generally are ER+/PR+/Her2/neu negative
• Usually present in advanced stages due to ana-
tomical reason
33.21 Zoledronic Acid • Adjuvant and metastatic therapy guidelines
are similar to female patients
• Zoledronic acid inhibits osteoclasts activity • Tamoxifen is the preferred option for adjuvant
and has been shown to reduce skeletal-related endocrine therapy
events
• Bisphosphonates may be helpful to reduce
loss of bone mineral density in patients with 33.26 Survival Stagewise
endocrine therapy for early breast cancer
• 5 year survival rates
–– Stage I: 98–100%
33.22 Follow Up –– Stage II: 90–93%
–– Stage III: 65–75%
• Every 3–6 months for first 2 years, then every –– Stage IV: 20–40%
6 months till 5 years and then annually • Nottingham prognostic index (NI) is calcu-
thereafter lated as follows: NI = (0.2 × size) + lymph
• In each visit clinical examination should be node stage + grade
done –– For lymph node stage, score 1 (if N0),
• Mammogram should be advised every year score 2 (if 1–3 LNs are positive), score 3 (if
4 or more LNs are positive).
–– For grading, score 1 (for grade 1), score 2
33.23 DCIS (for grade 2), and score 3 (for grade 3)

• The aim is of surgery is to achieve a margin

status of at least 1 mm 33.27 Recurrence
• Adjuvant radiotherapy following BCS reduces
local recurrence across all subgroups of • Chest wall recurrence—in patients with chest
women with DCIS. Radiotherapy has no effect wall recurrence due to the high risk of con-
on survival in DCIS comitant distant metastases, patients should
• Adjuvant hormone therapy is advocated in DCIS undergo full restaging, including assessment
• For treatment of LCIS, observation alone is of chest, abdomen, and bone. Chemotherapy
the preferred after first local or regional recurrence improves
• The pleomorphic variant of LCIS and LCIS long-term outcomes primarily in ER negative
with comedo necrosis—treated as DCIS disease. ET in this setting improves long-term
outcomes for ER positive disease.
• In metastatic recurrence—a biopsy should be
33.24 Inflammatory Breast Cancer advised from the lesion
–– Change in ER and HER2 receptor status
• Patients should receive neoadjuvant chemo- between the primary and metastatic site
therapy followed by mastectomy and ALND 10–13% and 3%
plus adjuvant RT with or without adjuvant hor- –– 8–10% show loss of ER expression and
mone, with or without adjuvant trastuzumab 2–3% with a gain in ER
• Immediate reconstruction is generally not –– HER2 gain occur slightly more frequently
recommended than HER2 loss (2–3% compared to 0–1%)
33 Case Carcinoma Breast 209

References conserving surgery on 10-year recurrence and 15-year

breast cancer death: meta-analysis of individual
patient data for 10,801 women in 17 randomised tri-
1. Mallick S, Benson R, Julka PK. Breast cancer pre-
als. Lancet. 2011;378(9804):1707–16.
vention with anti-estrogens: review of the cur-
3. The START Trialists’ Group. The UK Standardisation
rent evidence and future directions. Breast Cancer.
of Breast Radiotherapy (START) Trial A of radio-
2016;23(2):170–7.
therapy hypofractionation for treatment of early
2. Early Breast Cancer Trialists’ Collaborative Group
breast cancer: a randomised trial. Lancet Oncol.
(EBCTCG). Effect of radiotherapy after breast-­
2008;9(4):331–41.
 Oral Cavity Carcinoma
34
Prashanth Giridhar, Supriya Mallick,
and Goura K. Rath

Oral cavity carcinoma is a very common malig- 34.3 History Taking

nancy inflicting more commonly tobacco users.
• Ulcer/growth in oral cavity
• Pain at local site/radiation to ear/head
34.1 Risk Factors [1] • Bleeding from lesion
• Masses in neck
• Smoking • Tongue movement restriction—extrinsic mus-
• Smokeless tobacco cle involvement
• Alcohol • Regurgitation of food into nose—fistula on
• Betel nut chewing palate
• Premalignant lesions (leukoplakia 5% risk of • Loss of sensation over mental area—inferior
developing cancer, erythroplakia 50% risk) alveolar nerve in mandible involvement
• Older age • Difficulty in opening mouth—if long stand-
ing, sub-mucous fibrosis. If acute, pterygoid
muscle involvement
34.2 Sub-Sites • Ask history of smokeless tobacco use
• If young patients, sexual history
• Oral tongue—risk of bilateral nodal spread • If lip lesion, sun exposure
high. Risk of skip metastases present
• Mucosal lip—risk of nodal spread very low
(3–8%) 34.4 Examination
• Buccal mucosa
• Alveolar ridge 34.4.1 Local/Locoregional
• Retro molar trigone Examination: Check for
• Floor of moth—risk of bilateral nodal spread
high • Halitosis—anaerobic infection, necrotic
• Hard palate growth
• Trismus and grade of trismus
• Describe ulcer/growth—location, type, size,
extensions, feel on touch, bleeding
P. Giridhar (*) · S. Mallick · G. K. Rath • Skin involvement/fistula
Department of Radiation Oncology, National Cancer
Institute, All India Institute of Medical Sciences, • Bone involvement
New Delhi, India • If hard palate lesion. Check for fistula

© Springer Nature Singapore Pte Ltd. 2020 211

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_34
212 P. Giridhar et al.

• Systematic neck nodal examination (e) Retropharyngeal/Carotid sheath oedema

• Indirect laryngoscopy—to identify extension (f) Brightly enhancing parotid gland fol-
to base of tongue/synchronous lesions in lar- lowed by atrophy
ynx/hypopharynx
• Always note leukoplakia/erythroplakia
• Chest examination—to identify intercurrent 34.6 Staging
illness—COPD/emphysema
AJCC 2017 staging of oral cavity cancers is sum-
marised in Table 34.1
34.4.2 Differential Diagnosis

1. Malignancy 34.6.1 Treatment Overview [2, 3]

2. Tuberculosis
3. Syphilitic ulcer Treatment overview is summarised in Table 34.2

34.4.3 Workup 34.6.2 Brachytherapy Alone

1. Complete blood count Brachytherapy alone is an acceptable treatment

2. Liver and renal function tests in T1 and early T2 lesions with low risk of lymph
3. CEMRI face and neck (salient points detailed nodal spread (Eg: lip) with the following criteria
later) being met:
4. If MRI not feasible, CECT face and neck
5. Chest X-ray—PA view 1. Patient preference
2. Tumour in area of functional importance
(commissure)
34.5  EMRI Face and Neck of Oral
C 3. Tumour in area of cosmetic importance
Cavity (Important Points 4. Medical contraindications to surgery
for a Radiation Oncologist) 5. If previously irradiated and small recurrence

1. >1.5 T scan to be advised/preferred Doses1: HDR: 6 Gy per fraction, 2 fractions

2. Imaging to be done with puffed cheek—To per day till a total dose of 48 Gy
separate out mucosal surfaces        5 Gy per fraction, 2 fractions
3. The sequences needed—(a) Axial, sagittal, per day till a total dose of 45 Gy
coronal T1 weighted images. (b) T2 weighted Further details of brachytherapy are discussed
FSE with fat saturation. (c) Axial, sagittal, in brachytherapy chapter.
coronal post gadolinium T1 weighted images
with fat saturation
4. Differentiate myocutaneous flap from recur- 34.7  ombined External Beam
C
rence—flap has striations interposed with Radiotherapy (EBRT)
bright fat on T1 imaging while recurrence is and Brachytherapy
homogenous intermediate signal intensity
lesion without striations Combined EBRT and brachytherapy is an accept-
5. Normal post radiotherapy changes: able mode of treatment in:
(a) Thickened skin
(b) Reticular subcutaneous fat
(c) Brightly enhancing pharyngeal mucosa
(d) Bulky epiglottis 1
As per GEC ESTRO ACROP guidelines 2017.
34 Oral Cavity Carcinoma 213

Table 34.1 AJCC 2017 staging of oral cavity cancers

T stage N stage
Tis Carcinoma in situ N1 1 ipsilateral LN, <
_3 cm without ENE
1 ipsilateral/contralateral LN <_3 cm with
T1 Tumor <
_2 cm, <
_5 mm depth of invasion (DOI) N2a
ENE, 1 ipsilateral LN >3 cm <_6 cm without ENE

T2 Tumor <
_2 cm, DOI >5 mm and <
_10 mm or tumor >2 cm but <
_4 cm, and <
_10 mm
N2b >1 ipsilateral LN <
_6 cm without ENE
DOI
>1 ipsilateral/contralateral LN <
_6 cm without
N2c
ENE
T3 Tumor >4 cm or any tumor >10 mm DOI
N3a 1+ LN >6 cm without ENE

1 ipsilateral LN, >3 cm with ENE,

N3b
Moderately advanced local disease: (lip) tumor invades through cortical bone or 1+ ipsilateral/contralateral LN with ENE
involves the inferior alveolar nerve, floor of mouth, or skin of face (ie, chin or
T4a nose); (oral cavity) tumor invades adjacent structures only (eg, through cortical
bone of the mandible or maxilla, or involves the maxillary sinus or skin of the M stage
face); note that superficial erosion of bone/tooth socket (alone) by a
gingival primary is not sufficient to classify a tumor as T4

Very advanced local disease; tumor invades masticator space, pterygoid

T4b M1 Metastatic disease
plates, or skull base and/or encases the internal carotid artery
Summative Stage

N0 N1 N2 N3 M1

T1
I
T2
II
IVA
IVB IVC
T3
III

T4a

T4b

Table 34.2 Treatment overview for oral cavity cancers

Surgery
T1-2, N0 Resection of primary + ipsilateral neck dissection
T3N0, T1-4 N+ Resection of primary + bilateral neck dissection
Definitive radiation
T1-T2N0 Consider brachytherapy (in lip lesions)
Unresectable T4 lesions (high ITF above Mandibular Consider definitive chemoradiation (brachytherapy as part
notch, tongue lesion with base involvement) increases local control)
Adjuvant radiation
Positive margins Adjuvant chemoRT (cisplatin category I) if cannot
re-resect
ECE Adjuvant chemoRT
Other risk factorsa RT
pT3/T4, N2/N3, PNI, level IV/V, LVSI, DOI 4 mm or more for tongue, DOI 6 mm or more for floor of mouth
a

1. T1/T2 tumours with substantial risk of lymph 34.7.1 E

 xternal Beam Radiation
node spread (e.g. tongue) but patient unfit for Therapy
surgery
2. Locally advanced T3/T4 N+ tumours unsuitable • Timing: Should be started within 4–6 weeks of
for surgery due to poor functional outcome surgery
• Dose:
Doses (see footnote 1): HDR: 6 Gy per frac- –– High risk (close/positive margins/ECE)—
tion, 2 fractions per day till a total dose of 21 Gy 63–66 Gy in 30–33 fractions
      3 Gy per fraction, 2 fractions per –– High risk (tumour bed)—60 Gy in 30
day till a total dose of 18 Gy fractions
214 P. Giridhar et al.

–– Intermediate risk (operative bed)—54– and alveolar ridge without nodal disease
60 Gy in 30 fractions (Table 34.3).
–– Low risk—54 Gy in 30 fractions • Techniques: VMAT, IMRT with half beam
• Target: Tumour bed, operative bed, draining block and matched AP low neck field, IMPT.
lymphatics (levels I–IV, level V if node posi- 2D plan for a carcinoma tongue and a confor-
tive). Consider unilateral treatment for well mal plan for carcinoma buccal mucosa are
lateralized retro molar trigone, buccal mucosa shown in Figs. 34.1 and 34.2.

Table 34.3 Site specific nodal volumes to be included in radiotherapy

Sub site Stage Nodes in addition to involved nodes to be treated
Well lateralised T1/2, N0-N2a Ipsilateral I, II, III
Buccal mucosa, alveolus T3/4 Ipsilateral I–IV
Node > N2a Consider contralateral-III;
Include level V if level II or IV involved
Oral tongue, floor of mouth T1/T2 N0 Bilateral I–IV
IV optional for FOM
T3/4 N+ Bilateral I–V

Fig. 34.1 2D planning for post operative radiotherapy for oral tongue, with tongue bite using 2 lateral fields and a
single anterior beam

Fig. 34.2 Conformal plan for post op radiotherapy for buccal mucosa cancers
34 Oral Cavity Carcinoma 215

• Simulation: Supine, consider mouth opening high risk features (extracapsular extension,
tongue forward (oral tongue), tongue lateral- margin positivity, PNI or LVI); or oral cavity/
izing (buccal/alveolar/retromolar trigone) or oropharynx with LN+ at levels IV or V were
ramp (FOM) dental stent, Aquaplast mask. included. Adjuvant RT alone vs. RT + concur-
Wire scar. 3 mm bolus 2 cm around scar. rent cisplatin (100 mg/m2) was compared in
this randomised trial. RT dose 54 Gy/27# with
a boost to 66 Gy for high risk areas [5].
34.7.2 Follow-Up • Combined analysis showed patients with
extracapsular extension or margin positivity
• History/physical exam: Every 3 months for had a significant overall survival benefit with
1 year → every 4 months for 2nd year → every the addition of concurrent cisplatin [6].
6 months for 3rd year → yearly to 5 years (CT
Face and neck at 6 months and every 6 months
for 2 years) References
• Assess compliance with fluoride application,
neck/lymphedema exercises 1. Rivera C. Essentials of oral cancer. Int J Clin Exp
Pathol. 2015;8(9):11884–94.
2. Markopoulos AK. Current aspects on oral squamous
cell carcinoma. Open Dent J. 2012;6:126–30.
34.8 Important Trials 3. Omura K. Current status of oral cancer treatment
strategies: surgical treatments for oral squamous cell
carcinoma. Int J Clin Oncol. 2014;19(3):423–30.
34.8.1 A
 djuvant ChemoRT vs. RT: 4. Cooper JS, Pajak TF, Forastiere AA, Jacobs J,
EORTC 22931/RTOG 95-01 Campbell BH, Saxman SB, et al. Postoperative con-
current radiotherapy and chemotherapy for high-risk
• RTOG 95-01—416 patients with primary in squamous-cell carcinoma of the head and neck. N
Engl J Med. 2004;350(19):1937–44.
the oral cavity, oropharynx, larynx, hypophar- 5. Bernier J, Domenge C, Ozsahin M, Matuszewska K,
ynx with high risk features (2 or more positive Lefèbvre JL, Greiner RH, et al. Postoperative irradia-
lymph nodes, or extracapsular extension, or tion with or without concomitant chemotherapy for
margin positivity) were included. Adjuvant RT locally advanced head and neck cancer. N Engl J Med.
2004;350(19):1945–52.
alone vs RT with concurrent cisplatin (100 mg/ 6. Bernier J, Cooper JS, Pajak TF, van Glabbeke M,
m2) was compared. Radiotherapy dose was Bourhis J, Forastiere A, Ozsahin EM, et al. Defining
60 Gy/30# plus optional boost to 66 Gy [4]. risk levels in locally advanced head and neck can-
• EORTC 22931—Trial included 334 patients cers: a comparative analysis of concurrent postop-
erative radiation plus chemotherapy trials of the
with primary in oral cavity, oropharynx, hypo- EORTC (#22931) and RTOG (# 9501). Head Neck.
pharynx or larynx. T3-4 stage patients nega- 2005;27(10):843–50.
tive margins or T1-2 N2-3 or T1-2 N0-1 with
 Oropharynx Cancer
35
Nikhil P. Joshi and Martin C. Tom

35.1 History Taking • h/o immunodeficiency

• h/o previous radiation/chemotherapy.
• Neck swelling
• Otalgia
• Dysphagia
35.3 Examination
• Odynophagia
• Oral tongue fixation
• General nutritional status, performance status
• Trismus
• Oropharyngeal bleeding
• Voice change (“hot potato voice” with tongue Inspection
base cancer) 1. Inspect the entire oral cavity and oropharynx
• Weight loss, fevers, or night sweats with special attention to the tongue
• Dyspnea. 2. Assess tongue for bulk, fasciculations and
tongue deviation on protrusion. Inability to
protrude the tongue may indicate deep muscu-
35.2 Other Relevant History lature involvement
3. Assess bilateral anterior and posterior tonsil-
• h/o tonsillectomy, thyroid surgery, or other lar pillars, soft palate, and uvula
head and neck surgeries 4. Assess extent of tonsil primaries (size,
• h/o medical co-morbidities (including renal involvement of tongue base, soft palate, and
dysfunction or hearing loss) distance from midline)
• Social support 5. Assess for trismus which may indicate ptery-
• h/o smoking (pack years) goid muscle involvement.
• h/o alcohol intake
• h/o smokeless tobacco, drug abuse Palpation
• h/o high risk sexual behavior, total lifetime 1. Palpate the glossotonsillar sulcus and tongue
sexual partners base for firmness/mass
2. Palpate the oral tongue for submucosal
involvement
N. P. Joshi (*) · M. C. Tom
Cleveland Clinic Foundation, Cleveland, OH, USA 3. Palpate the soft palate (difficult due to gag
e-mail: joshin@ccf.org reflex—use local anesthetic)

© Springer Nature Singapore Pte Ltd. 2020 217

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_35
218 N. P. Joshi and M. C. Tom

4. Palpate bilateral necks one at a time starting • Lymphoma

with the normal side if applicable from cranial • Minor salivary gland tumor
to caudal extent including the parotid, sub- • Sarcoma
mental, and submandibular nodal areas • Tonsillitis
• Tongue base/vallecula cyst
• AV malformation
35.3.1 Flexible Endoscopy
in the Office
35.5 Work-Up
Performed in the sitting position with neck in
neutral position; 2% lidocaine is sprayed in the • CBC, RFT, LFT
nares and oral cavity. Adequate time is allowed • Core biopsy/punch biopsy of the primary
for anesthesia to take effect. The flexible endo- lesion during examination under anesthesia
scope lubricated with lidocaine gel is advanced (with p16 IHC)
through the nares. Serial inspection of the fol- • Core biopsy of an enlarged lymph node (with
lowing structures is performed—the opening of p16 IHC)
the Eustachian tubes, torus tubarius, fossa of • Contrast enhanced CT neck
Rosenmuller, nasal aspect of the soft palate, • Contrast enhanced MRI of the neck (in select
tongue base, and vallecula (patient is asked to situations)
protrude the tongue and mandible). The glos- • Whole body PET CT
sotonsillar sulcus is also inspected. The supra- • Comprehensive dental evaluation (extractions
glottic/glottic/hypopharyngeal structures are must be completed 14–21 days before
also inspected (aryepiglottic folds, piriform radiation)
sinuses, post-cricoid space, false vocal cords, • Comprehensive audiometry
ventricles, true vocal cords, and subglottis). • Speech and swallow evaluation
Tongue base and vallecula masses are often • Smoking cessation counselling [1].
submucosal.

35.6 Staging
35.3.2 Examination of the CNS
AJCC 2017 staging for HPV related and HPV
• Particular attention must be given to the exam- negative oropharyngeal cancer is summarized in
ination of cranial nerves depending upon the Tables 35.1 and 35.2.
extent of disease.

35.7 Treatment Outline

35.3.3 Systemic Examination
Treatment for oropharynx cancer does not differ
• Relevant systemic examination should be by HPV status. While treatment de-­intensification
done in addition to general ear, nose, and approaches are being explored for low risk HPV+
throat examination. oropharyngeal tumors, these approaches are cur-
rently investigational and are discouraged outside
of a clinical trial.
35.4 Differential Diagnosis Early oropharynx cancer (AJCC 7th edition:
for Oropharyngeal Cancer T1-2, N0-1)

• Oropharyngeal carcinoma (HPV positive or • Unimodality treatment is favored with either

negative) radiation or surgery alone
35 Oropharynx Cancer 219

Table 35.1 AJCC 8th ed., 2017 oropharynx-HPV related

Clinical and pathologic staging: AJCC 8th ed., 2017 oropharynx (HPV related) [14]
T0 No primary identified NX Regional lymph nodes I cT0-­T2 cN0-­N1 M0
cannot be assessed pT0-­T2 pN0-­1
T1 ≤2 cm in greatest dimension cN1 One or more ipsilateral II cT0-­T2 cN2 M0
lymph nodes, none >6 cm cT3 cN0-­N2
pT0-­T2 pN2
pT3-­T4 pN0-­N1
T2 >2 but not >4 cm in greatest cN2 Contralateral or bilateral III cT0-­T4 cN3 M0
dimension lymph nodes, none >6 cm cT4 cN0-3
pT3-­T4 pN2
T3 >4 cm in greatest dimension or cN3 Lymph node(s) >6 cm IV Any T Any N M1
extension to the lingual surface of
the epiglottis
T4 Moderately advanced local disease pN1 ≤4 lymph nodes involved
Tumor invades the larynx, extrinsic pN2 >4 lymph nodes involved
muscle of tongue, medial pterygoid, M1 Distant metastasis
hard palate, or beyonda
a
Mucosal extension to lingual surface of the epiglottis from primary tumors of the base of the tongue and vallecula does
not constitute invasion of the larynx

Table 35.2 AJCC 8th ed., 2017 Oropharynx-p16 negative

Clinical staging: AJCC 8th ed., 2017 oropharynx (p16 negative) [14]
TX Primary tumor cannot be assessed NX Regional lymph nodes cannot be
assessed
Tis Carcinoma in situ N0 No regional lymph node
metastasis
T1 ≤2 cm in greatest dimension N1 Metastasis in a single ipsilateral 0 Tis N0 M0
lymph node ≤3 cm in greatest
dimension and ENE(−)
T2 >2 but not >4 cm in greatest N2a Metastasis in a single ipsilateral I T1 N0 M0
dimension lymph node >3 cm but not >6 cm
in greatest dimension and
ENE(−)
T3 >4 cm in greatest dimension or N2b Metastasis in multiple ipsilateral II T2 N0 M0
extension to the lingual surface of the lymph nodes, none >6 cm in
epiglottisa greatest dimension and ENE(−)
N2c Metastasis in bilateral or
contralateral lymph nodes, none
>6 cm in greatest dimension and
ENE(−)
T4a Tumor invades the larynx, deep/ N3a Metastasis in a lymph node III T3 N0 M0
extrinsic musculature of the tongue, >6 cm in greatest dimension and T1-­ N1 M0
medial pterygoid, hard palate, or ENE(−) 3
mandible
T4b Tumor invades the lateral pterygoid N3b Clinically overt ENE(+) IVA T4a N0-­ M0
muscle, pterygoid plates, lateral 1
nasopharynx, skull base, or encases T1-­ N2 M0
carotid artery 4a
IVB T4b Any M0
Any N3 M0
M1 Distant metastasis IVC Any Any M1
a
Mucosal extension to lingual surface of the epiglottis from primary tumors of the base of the tongue and vallecula does
not constitute invasion of the larynx
220 N. P. Joshi and M. C. Tom

Locally advanced oropharynx cancer (AJCC • Patients who would require a more extensive
7th edition: T3-4, N0-N3 or T1-2, N2a-N3) surgery are favored to be treated with defini-
tive chemoradiation. Surgery (combined with
• Bimodality treatment is favored with either free flap reconstruction) is typically reserved
concurrent chemoradiation or surgery fol- for salvage in this setting.
lowed by adjuvant radiation
• Appropriate case selection should avoid tri-
modality treatment but this might be neces-
35.9 Radiotherapy
sary for selected cases (chemoradiation
and Chemotherapy
followed by salvage neck dissection for high
nodal burden or surgery followed by radiation
• T1-2, N0-N1 (AJCC 7th edition) oropharyn-
with concurrent chemotherapy for ECE or
geal cancers can be treated with definitive
positive margins)
radiation alone (70 Gy in 35 fx or 66 Gy in 30
fractions to gross disease) [2]
Recurrent non-metastatic disease amenable to
–– Dose to the elective neck is typically 56 Gy
curative therapy
in 35 fractions or 54–60 Gy in 30 fractions,
respectively
• Surgical salvage followed by aggressive adju-
• More advanced cases are treated with either
vant re-irradiation with or without
definitive chemoradiation or surgery followed
chemotherapy
by adjuvant radiation or chemoradiation
Incurable oropharynx cancer (metastatic or • Definitive radiation is usually 70 Gy in 35
non-metastatic) not amenable to curative therapy fractions with concurrent high dose cisplatin
chemotherapy (100 mg/m2) [3]
• Cisplatin-based palliative chemotherapy –– Dose to the elective neck is typically 56 Gy
• Palliative immunotherapy in 35 fractions delivered simultaneously
• Palliative radiation (conventional, Quad Shot, or • Cisplatin ineligible patients are treated with
stereo tactic body radiotherapy for select cases) concurrent cetuximab (400 mg/m2 loading
• Palliative surgery in select cases. dose followed by 250 mg/m2 weekly) [4, 5]
• Chemotherapy/Cetuximab ineligible patients
may be treated with altered fractionated radia-
35.8 Surgery tion (70 Gy in 35 fractions over 6 weeks or
hyperfractionation 81.6 Gy in 68 fractions at
• Early stage oropharyngeal cancers amenable 1.2 Gy twice a day 6 h apart) [6, 7].
to transoral resection are treated with this
approach along with an ipsilateral modified
radical neck dissection 35.10 EBRT IMRT Planning
• Ideal cases include well lateralized, well-­
defined primaries with minimal nodal burden • IMRT is strongly recommended for all cases
(without clinical ECE, <N2b nodal disease • In general, GTV = all disease noted on exam
AJCC 7th edition), in medically fit patients and radiology (include flexible endoscopy
with adequate mouth opening exam; image fusion with available imaging is
• Tonsil primaries should ideally be away from highly recommended)
the carotid artery (a medialized carotid is not • CTV high dose = GTV + 5 mm margins
favored); the node and primary should prefer- (shaved off air, bone and other uninvolved
ably be separated structures) (Fig. 35.1)
• Well-selected cases may be treated with sur- • CTV low dose = GTV + 10 mm margins (shaved
gery followed by adjuvant radiation in order to off air, bone and uninvolved structures and
avoid chemotherapy includes structures based on the “T” stage) [8]
35 Oropharynx Cancer 221

35.11 OAR

• It is highly recommended that the following

set of OARs is delineated for each case (brain-
stem, brainstem PRV3mm, cochlea, spinal
cord, spinal cord PRV 5 mm, parotids, sub-
mandibular glands, lips, oral cavity, mandible,
oropharynx, supraglottis, larynx or glottic-­
supraglottis, esophagus, trachea, and brachial
plexus)
• Additional structures like eyes, lens, optic
nerves, chiasm, and temporal lobes may be
added for individual cases
• It is recommended that doses to each of the
OARs be reduced as much as possible without
compromising PTV coverage—guidance for
dose constraints may be found in current
Fig. 35.1 GTV (red), high dose CTV (purple), and low RTOG protocols (e.g., RTOG 1016) [5].
dose CTV (gold) in a patient with carcinoma of the right
tongue base

35.12 Re-Irradiation and SBRT

• CTV low dose will also include relevant nodal
contours (retropharyngeal nodes and levels II– • Select cases may be amenable to re-irradiation
IV bilaterally for most cases) after salvage surgery or SBRT—this discus-
• The contralateral elective neck may be omit- sion is outside the scope of this chapter.
ted in cases where the contralateral neck is
node negative and the primary is located in the
tonsil, “T” stage T1-2, well lateralized (>1 cm 35.13 Palliative RT
from midline), and with <1 cm superficial
involvement of the soft palate or base of • Standard palliative fractionation schemes
tongue with limited nodal burden (N0-N2a include 8 Gy in 1 fraction, 20 Gy in 5 frac-
disease per AJCC 7th edition; N2b disease is tions, 30 Gy in 10 fractions, or Quad Shot
discretionary) [9] approach (14 Gy in 4 fractions; 2 fractions a
• Contralateral retropharyngeal nodes may be day 6 h apart over 2 days repeated q 4 weeks
omitted for the node negative contralateral up to 3 times)
neck with a well-lateralized ipsilateral
primary
• Level IB may be omitted if only one level in 35.14 Follow-Up
the neck is positive and the “T” stage is
T1-2 • First follow-up: PET CT [10] is recommended
• Level V may be omitted if only one level in with a contrast enhanced CT neck at 3 months
the neck is positive and the involved node is after definitive treatment while CT neck and
anterior to the internal jugular vein and carotid chest with contrast are recommended at
artery 3 months after adjuvant radiation/adjuvant
• PTVs = CTV + 3 mm margin when using chemoradiation along with a detailed history
daily image guidance with cone beam CT. and physical exam
222 N. P. Joshi and M. C. Tom

• Further follow-up is scheduled every 3 months References

for the first 2 years, every 6 months for the
next 3 years, and annually thereafter 1. NCCN Clinical Practice Guidelines in Oncology:
• Further imaging of the neck is directed by Smoking Cessation. https://www.nccn.org/pro-
fessionals/physician_gls/pdf/smoking.pdf. 2018.
symptoms or post-treatment imaging; low Accessed 23 Dec 2018.
dose CT chest is recommend for former/cur- 2. Eisbruch A, Harris J, Garden AS, et al. Multi-­
rent smokers [11] institutional trial of accelerated hypofractionated
• Regular dental follow-up, smoking cessation, intensity-modulated radiation therapy for early-stage
oropharyngeal cancer (RTOG 00-22). Int J Radiat
speech and swallowing physiotherapy, and Oncol Biol Phys. 2010;76(5):1333–8.
enrolment into a survivorship clinic are 3. Pignon JP, le Maitre A, Maillard E, Bourhis J. Meta-­
recommended analysis of chemotherapy in head and neck can-
• Thyroid stimulating hormone every cer (MACH-NC): an update on 93 randomised
trials and 17,346 patients. Radiother Oncol.
6–12 months if the neck is irradiated. 2009;92(1):4–14.
4. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy
plus cetuximab for squamous-cell carcinoma of the
35.15 Oncologic Outcomes head and neck. N Engl J Med. 2006;354(6):567–78.
5. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy
plus cetuximab or cisplatin in human papillomavirus-­
• The survival and locoregional control for HPV positive oropharyngeal cancer (NRG Oncology RTOG
related oropharyngeal cancer is better than 1016): a randomised, multicentre, non-­ inferiority
HPV unrelated oropharyngeal cancer (stage trial. Lancet. 2019;393:40.
for stage) 6. Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy
Oncology Group (RTOG) phase III randomized study
• 3-year overall survival rates per the risk strati- to compare hyperfractionation and two variants of
fication (included HPV related and unrelated accelerated fractionation to standard fractionation
oropharynx cancer) by Ang et al. [12]: (a) low radiotherapy for head and neck squamous cell carci-
risk, 93% (b) intermediate risk, 70.8%, and (c) nomas: first report of RTOG 9003. Int J Radiat Oncol
Biol Phys. 2000;48(1):7–16.
high risk, 46.2% 7. Lacas B, Bourhis J, Overgaard J, et al. Role of
• 3-year locoregional and distant control, radiotherapy fractionation in head and neck cancers
respectively, per risk stratification (HPV (MARCH): an updated meta-analysis. Lancet Oncol.
related oropharyngeal cancer) by O’Sullivan 2017;18(9):1221–37.
8. Gregoire V, Evans M, Le QT, et al. Delineation of
et al. [13]: (a) low risk, 95% and 93% (b) high the primary tumour Clinical Target Volumes (CTV-­
risk, 82% and 76% P) in laryngeal, hypopharyngeal, oropharyngeal
• 3-year locoregional and distant control, and oral cavity squamous cell carcinoma: AIRO,
respectively, per risk stratification (HPV unre- CACA, DAHANCA, EORTC, GEORCC, GORTEC,
HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC
lated oropharyngeal cancer) by O’Sullivan CTG, NCRI, NRG Oncology, PHNS, SBRT,
et al. [13]: (a) low risk, 76% and 93% (b) high SOMERA, SRO, SSHNO, TROG consensus guide-
risk, 62% and 72% lines. Radiother Oncol. 2018;126(1):3–24.
• Oropharynx overall survival and progression 9. Yeung AR, Garg MK, Lawson J, et al. ACR
Appropriateness Criteria(R) ipsilateral radiation for
free survival calculator by NRG Oncology squamous cell carcinoma of the tonsil. Head Neck.
https://www.nrgoncology.org/Nomograms/ 2012;34(5):613–6.
Oropharynx-Cancer-Overall-Survival- 10. Mehanna H, Wong WL, McConkey CC, et al.
Calculator PET-CT surveillance versus neck dissection in
advanced head and neck cancer. N Engl J Med.
2016;374(15):1444–54.
Source of Images The image was taken from a 11. Aberle DR, Adams AM, Berg CD, et al. Reduced lung-­
patient treated by authors as per hospital protocol cancer mortality with low-dose computed tomographic
and consent was taken. screening. N Engl J Med. 2011;365(5):395–409.
35 Oropharynx Cancer 223

12. Ang KK, Harris J, Wheeler R, et al. Human papillo- ing to minimal risk of distant metastasis. J Clin Oncol.
mavirus and survival of patients with oropharyngeal 2013;31(5):543–50.
cancer. N Engl J Med. 2010;363(1):24–35. 14. Edge SB. American Joint Committee on Cancer.
13. O’Sullivan B, Huang SH, Siu LL, et al. AJCC cancer staging manual. 8th ed. New York:
Deintensification candidate subgroups in human Springer; 2017.
papillomavirus-­related oropharyngeal cancer accord-
 Laryngeal Cancer
36
Subhas Pandit and Simit Sapkota

36.1 History Taking 36.3 Examination

• Hoarseness—usually the first sign of glottic 36.3.1 Physical Exam

cancer, glottic tumor becomes symptomatic
earlier than supraglottic, so detected in earlier Complete head and neck exam.
stage
• Throat pain, dysphagia, odynophagia
• Neck nodes 36.3.2 Palpation for Cervical Nodes
• Symptoms of airway obstruction—Stridor,
dyspnea in advanced stage • Localized pain/tenderness or bulge over ala of
• Referred otalgia is sign of advanced disease cartilage suggests thyroid cartilage invasion
(involvement of CN X) • Disappearance of laryngeal crepitus suggests
• Tobacco use (smoking, chewing), bidi, mari- postcricoid involvement.
juana use
• History of alcohol use.
36.3.3 Indirect Laryngoscopy

36.2 Other Relevant History Direct laryngoscopy (examination under anesthe-

sia): Evaluate tumor extent, look for second pri-
• History of respiratory illness mary, biopsy and feasibility of conservation
• Past history of radiation exposure larynx surgery.
• Medical comorbidity (including renal dys-
function, hearing loss).
36.3.4 Fiber-Optic Flexible
Endoscopy

For early laryngeal lesions, narrow band imaging

endoscopy may also be used to better assess the
S. Pandit (*) · S. Sapkota
mucosal infiltration if available [1]
Department of Radiation Oncology, Kathmandu
Cancer Center, Kathmandu, Nepal Speech pathology review—For assessment as
e-mail: dr.subhas@kccrc.org well as post-treatment planning.

© Springer Nature Singapore Pte Ltd. 2020 225

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_36
226 S. Pandit and S. Sapkota

36.4 Investigations • T1b: Tumor involves both vocal cords

• T2: Tumor extends to supraglottis and/or sub-
• CBC, RFT (For cisplatin), CCT, audiology glottis and/or with impaired vocal cord
evaluation mobility
• Biopsy • T3: Tumor limited to the larynx with vocal
• USG neck to evaluate cervical cord fixation and/or invades paraglottic space,
lymphadenopathy and/or invasion of inner thyroid cartilage
• CT scan is gold standard. Extent of disease, pre- • T4a: same as supraglottis
epiglottic and paraglottic involvement, extra- • T4b: same as supraglottis.
laryngeal spread, thyroid cartilage involvement,
assessment of lymphadenopathy is done. N, M stage and stage grouping as in oral cavity
• MRI imaging is complimentary. It is preferred tumors (Chap. 35).
for evaluation of soft tissue extent but suscep-
tible to motion
• Chest X-ray—to look for pulmonary pathol- 36.6 Treatment Outline
ogy as well as metastasis.
• PET-CT may be used for metastatic workup in Apart from cure, preservation of laryngeal func-
advanced cancers, or in patients having high-­ tion is an important aim of treatment. Laryngeal
suspicion of distant metastasis. functions are airway protection, phonation, and
respiration.

36.5 Staging
36.7 Early Glottic Cancer
36.5.1 T Staging Supraglottis
• T1/T2 glottic cancer can be treated by RT,
• T1: Tumor limited to 1 subsite of supraglottis transoral laser surgery, or conservation laryn-
with normal vocal cord mobility geal surgery.
• T2: Tumor invades more than 1 adjacent sub- • Although there is insufficient evidence regard-
site of supraglottis or glottis or region outside ing superiority of one modality over other it is
the supraglottis without fixation of the larynx generally agreed that RT gives best voice
• T3: Tumor limited to larynx with vocal cord quality.
fixation and/or invading the postcricoid area, • Patient who fails after radiotherapy can be
pre-epiglottic tissues, paraglottic space, and/ salvaged with surgical modality and vice
or invasion of inner thyroid cartilage versa.
• T4a: Tumor invades through the thyroid carti- • Radiotherapy failure can be salvaged with
lage, and/or invades the trachea, soft tissues of partial laryngectomy in suitable patients. Total
the neck including deep extrinsic muscle of the laryngectomy can be a salvage option after RT
tongue, strap muscles, thyroid, or esophagus or conservation laryngectomy.
• T4b: Tumor invades prevertebral space,
encases carotid artery, or invades mediastinal
structures. 36.8 T3 Laryngeal Cancer

• Treatment of T3 laryngeal cancer is somewhat

36.5.2 T Staging Glottis controversial; they can be generally divided
into two groups.
• T1: Tumor limited to the vocal cord, with nor- • Favorable group have small volume unilateral
mal mobility disease, have good airway, and have reliable
• T1a: Tumor limited to 1 vocal cord follow-up. These patients are candidate for
36 Laryngeal Cancer 227

larynx preservation and are offered concurrent • Patients unfit for concurrent chemoradiother-
chemoradiotherapy with surgery as salvage. apy can be treated with concurrent cetuximab-­
• Unfavorable patients fare better with upfront radiotherapy or altered fractionation
total laryngectomy. Most of these patients radiotherapy.
require postoperative radiotherapy. • Surgical option is supraglottic laryngectomy
• Indications of postoperative radiotherapy are with selective neck dissection.
close or positive margins, significant subglot- • If laryngeal function is compromised—Near-­
tic extension (1 cm or more), cartilage inva- total or total laryngectomy with selective neck
sion, perineural invasion, extension of the dissection and adjuvant (chemo)-radiotherapy.
primary tumor into the soft tissues of the neck,
multiple positive neck nodes.
• Patients having extracapsular extension of 36.12 Supraglottis T4 Tumor
lymph node or positive margin benefit from
postoperative chemo-radiation. • Near-total or total laryngectomy with selec-
tive neck dissection and adjuvant (chemo)-
radiotherapy is preferred.
• Definitive RT for those who refuse total laryn-
36.9 Advanced Laryngeal Cancer (T4)
gectomy or medically unfit patients.
• T4 patients are offered upfront total laryngec-
Upfront neck dissection followed by definitive
tomy + B/L selective node dissection (level
chemo-radiotherapy for small primary tumor
2.3.4), usually followed by postoperative RT.
with large neck node has been attempted but
• Definitive RT for those who refuse total laryn-
lacks high-quality evidence [2].
gectomy or medically unfit patients.
• Even if disease is controlled, patient may have
dysfunctional larynx and will require trache-
ostomy and feeding tube.
36.13 Radiotherapy Technique

T1 glottis tumor is traditionally treated with limited

opposed lateral fields should consist of a 5 × 5 cm
36.10 S
 upraglottis Stage I and II
square extending to the bottom of the hyoid bone or
(T1/T2)
the top of the thyroid notch superiorly, the bottom
of the cricoid inferiorly, the anterior edge of the
• Supraglottis has rich-lymphatic supply and
vertebral bodies posteriorly, and 1 cm flash anteri-
risk of nodal spread is much higher than glot-
orly. For T2 field was extended accordingly.
tic tumor. Management decision therefore
Carotid sparing technique using IMRT is being
includes management of neck as well.
explored in these tumors which may translate to
• Radical radiotherapy is preferred modality.
reduced incidence of carotid artery stenosis.
• Transoral laser microsurgery and supraglottic
For all other stages 3D CRT or IMRT is
partial laryngectomy are other treatment
recommended.
options.

36.13.1 CT Simulation

36.11 T3 Supraglottis Tumors
• Supine with flat table top, use thermoplastic
• If laryngeal function is intact—organ conser- mask for immobilization
vation approach with concurrent chemoradio- • Neutral head position and CT thickness of
therapy is preferred. 2–3 mm is recommended
228 S. Pandit and S. Sapkota

• Scanned from above base of skull to below piriform sinus postero-laterally. Excludes
sternoclavicular joint extra-laryngeal tissue, oropharynx, and poste-
• IV contrast should be used.(May be omitted in rior pharyngeal wall.
T1 glottic cancer) • T4 tumor CTV-P2 includes part of the thyroid
• Co-registration with MRI is not much helpful cartilage in relation to the GTV-T, part of the
in this site. cricoid cartilage caudally, and the pre-­
epiglottic space, anteriorly; extends outside of
the thyroid cartilage, but it does not go beyond
36.13.2 T
 arget Delineation in 3D the strap muscles (sterno-thyroid or thyro-­
Conformal/IMRT [3] hyoid muscles). Includes part of the thyroid
gland. Excludes hyoid and vertebral body,
Following terminology is used as recommended however vertebral body included if preverte-
by consensus guideline for delineation of pri- bral space involvement (T4b).
mary tumor.

• GTV-P: delineated from clinical and imaging 36.14 S

 upraglottic Tumor: Target
assessment. Volumes
• CTV-P1: High risk CTV, correspond to GTV-P
plus a 5 mm margin and prescribed to highest • T1/T2: CTV-P2 typically includes pre-­
dose. epiglottic space and para-glottic space, glottis
• CTV-P2: Intermediate risk CTV, correspond in tumor of ventricle, vallecula in tumor of
to GTV-P plus a 10 mm margin and prescribed AEF/suprahyoid epiglottis. Excludes thyroid
to intermediate/prophylactic dose. cartilage and air cavity of laryngo-pharynx
• CTVs are modified excluding air cavities and and in arytenoid tumors—posterior pharyn-
considering anatomical barrier like bone, car- geal wall
tilage, or fascia. • T3 tumors: CTV P2 typically includes post-­
cricoid area in addition to the above
structures
36.13.3 G
 lottic Tumor Target • T4 tumor: CTV P2 includes thyroid cartilage
Volumes but is limited by strap muscle and part of thy-
roid gland.
• In superficial glottis cancer (T1 or early T2),
only one CTV can be drawn with 5 mm isotro- Subglottic tumor: They are rare as constitute
pic expansion of GTV. only ~5% of laryngeal tumors. However, princi-
• T1 tumor: CTV typically includes para glottis ple of contouring primary tumor is similar to
space, anterior commissure in anterior cord other laryngeal tumors.
tumor, anterior part of contralateral cord for
tumor extending to anterior commissure,
vocal process of the arytenoid cartilage for 36.14.1 Nodal Target Volume [4]
tumor extending to the posterior vocal cord,
excludes thyroid cartilage and air cavity. • CTV 70 involved nodes are included in this
• T2 tumor: CTV-P2 typically includes cranial volume and in selected cases nodes adjacent
part of subglottis, the ipsilateral ventricle, and to the tumor
the caudal part of the supra-glottic mucosa in • Elective nodes in T1/2 N0 glottis—None
addition to the abovementioned structures. • Elective T1/2 supraglottis—Bilateral level II,
• T3 tumor CTV-P2 usually includes part of cri- III
coid cartilage caudally, the pre-epiglottic • Elective T3-4NO glottis/supraglottis—
space anteriorly, and the medial wall of the Bilateral level II, III, and IV.
36 Laryngeal Cancer 229

36.14.2 Dose/Fractionation References

• Glottis: 63 Gy in 28 fractions or 65.25 Gy in 29 1. Bertino G, Cacciola S, Fernandes WB Jr, Fernandes

CM, Occhini A, Tinelli C, et al. Effectiveness of nar-
fractions for T1N0 and T2N0 tumors, respec-
row band imaging in the detection of premalignant
tively [5]. Alternatively, 66 Gy in 33 fractions and malignant lesions of the larynx: validation of a
or 70 Gy in 35 fractions, respectively. new endoscopic clinical classification. Head Neck.
• For T3/T4: 70 Gy in 35 fractions 2015;37:215–22.
2. Elicin O, et al. Up-front neck dissection followed
• Postoperative: 60 Gy in 30 fractions
by definitive (chemo)-radiotherapy in head and
• High risk post-operative: 66 Gy in 33 neck squamous cell carcinoma: rationale, com-
fractions. plications, toxicity rates, and oncological out-
comes – a systematic review. Radiother Oncol.
2016;119(2):185–93.
3. Grégoire V, Evans M, Le Q-T, Bourhis J, Budach
36.15 Chemotherapy V, Chen A, et al. Delineation of the primary
tumour Clinical Target Volumes (CTV-P) in laryn-
geal, hypopharyngeal, oropharyngeal and oral
• Preferred regimen for organ conservation is cavity squamous cell carcinoma: AIRO, CACA,
concurrent radiotherapy with cisplatin DAHANCA, EORTC, GEORCC, GORTEC,
100 mg/m2 every 3 weekly as demonstrated by HKNPCSG, HNCIG, IAG-­KHT, LPRHHT, NCIC
CTG, NCRI, NRG Oncology, PHNS, SBRT,
RTOG 9111 study [6].
SOMERA, SRO, SSHNO, TROG consensus guide-
• Induction chemotherapy has been employed lines. Radiother Oncol. 2018;126(1):3–24. https://
in larynx preservation protocol [7]. However, doi.org/10.1016/j.radonc.2017.10.016.
their role is still controversial as none of trials 4. Biau J, et al. Selection of lymph node target volumes
for definitive head and neck radiation therapy: a 2019
have shown survival gain compared to concur-
Update. Radiother Oncol. 2019;134:1–9.
rent RT + CT. When induction regimen is used 5. Yamazaki H, Nishiyama K, Tanaka E, et al.
3 drug combination is recommended [8]. Radiotherapy for early glottic carcinoma (T1N0M0):
• RT + Cetuximab has survival benefit compared results of prospective randomized study of radiation
fraction size and overall treatment time. Int J Radiat
to RT alone and is recommended for patients
Oncol Biol Phys. 2006;64:77–8.
who cannot tolerate chemotherapy [9]. 6. Forastiere AA, Zhang Q, Weber RS, et al. Long-term
results of RTOG 91-11: a comparison of three non-
surgical treatment strategies to preserve the larynx in
patients with locally advanced larynx cancer. J Clin
36.16 Follow-Up Oncol. 2012;31(7):845–52.
7. Wolf GT, Fisher SG, The Department of Veterans
• Follow-up is scheduled every 3 months for the Affairs Laryngeal Cancer Study Group, et al.
Induction chemotherapy plus radiation com-
first 2 years, every 6 months for the next pared with surgery plus radiation in patients
3 years, and annually thereafter. with advanced laryngeal cancer. N Engl J Med.
• Further imaging of the neck is directed by 1991;324:1685–90.
symptoms or post-treatment imaging; low 8. Lorch JH, Goloubeva O, Haddad RI, et al. Induction
chemotherapy with cisplatin and fluorouracil alone
dose CT chest is recommended for former/ or in combination with docetaxel in locally advanced
current smokers. squamous-cell cancer of the head and neck: long-­
• Regular dental follow-up, smoking cessation, term results of the TAX 324 randomised phase 3 trial.
speech and swallowing physiotherapy and Lancet Oncol. 2011;12(2):153–9.
9. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones
nutritional rehabilitation, screening for CU, Sur RK, et al. Radiotherapy plus cetuximab for
depression, and enrolment into a survivorship locoregionally advanced head and neck cancer, 5-year
clinic are recommended. survival data from a phase 3 randomised trial, and
• CXR annually. Thyroid stimulating hormone relation between cetuximab-induced rash and sur-
vival. Lancet Oncol. 2009;6(11):21–8.
every 6–12 months if the neck is irradiated.
 Parotid Tumour
37
V. R. Anjali

37.1 History Taking 37.3 Examination

• Swelling in front/below the ear 37.3.1 General Examination

• Rapidly enlarging swelling (malignant)
• Pain (involvement of deep structures) • Performance status
• Cranial nerve involvement (CN VII, V2, V3, • Built and nourishment
IX, X, XI, XII) • Pallor, icterus, clubbing, cyanosis, lymphade-
• Skin changes (cutaneous and mucosal nopathy, pedal oedema
surface) • Vitals—pulse rate, blood pressure, tempera-
• Neck swellings ture, respiratory rate.
• Trismus (pterygoid plate involvement).
• Fixity to surrounding structures
• Ear symptoms 37.3.2 Local Examination
• Fever/bilateral swelling.
37.3.2.1 Inspection
• Facial asymmetry
37.2 Other Relevant History • Swelling
• Erythema/skin changes
• History of exposure to ionising radiation, • Mouth opening.
ultraviolet exposure (dose response effect) • Facial nerve palsy
• Previous surgery for parotid • External auditory canal.
• Occupational exposure to hair dye, silica,
nickel 37.3.2.2 Palpation
• Smoking associated with Warthin’s tumour. • Size, location, margins with respect to bony
landmark, consistency, fixity, skin over the
swelling
• Movement of jaw
• Facial nerve examination
V. R. Anjali (*)
• Examination of neck nodes: size, number,
Department of Radiation Oncology, All India Institute nodal level, laterality, consistency, fixity, mar-
of Medical Sciences, New Delhi, India gins, skin over the swelling.

© Springer Nature Singapore Pte Ltd. 2020 231

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_37
232 V. R. Anjali

37.3.3 Examination of Other Systems Open biopsy/excision biopsy is contraindicated

in view of tumour seeding and facial nerve injury.
• Central nervous system: Higher mental function, Investigations to know local disease extent are
cranial nerve examination, sensory system, summarised in Table 37.1.
motor system, skull and spine examination.
• Respiratory system
• Gastrointestinal system 37.6 Pathology
• Cardiovascular system.
Common histological subtypes of salivary
gland tumours are summarised in Table 37.2
37.4 Differential Diagnosis and histological grades are summarised in
Table 37.3.
• Malignant tumour of parotid
• Benign lesions of parotid (pleomorphic ade-
noma, Warthin’s tumour) 37.7 Staging-AJCC 08
• Parotitis/calculi
• Tuberculosis AJCC 2017 staging for salivary gland tumours is
• Autoimmune disease summarised in Table 37.4.
• Lymphoma. Lymph nodal spread: intra-parotid, peri-­
parotid, pre-auricular, submandibular upper and
mid jugular nodes, apex of the posterior triangle
37.5 Work-Up (level V) nodes, and occasionally to retropha-
ryngeal nodes. Table 37.5 summarises the risk
Baseline Complete blood counts of lymph node risk as per histological subtype.
investigation Liver function test (LFT)
Renal function test (RFT)
Serum electrolyte
Chest X-ray
37.8 Treatment
FNAC High sensitivity (87–96%) and
specificity (90–97%) Surgery—Well planned and carefully executed.

Table 37.1 Radiological investigations to know locoregional disease extend

Ultrasonography face and High sensitivity—95–100% Not useful if deep lobe is involved or if para
neck Malignancy suspected pharyngeal extension is present or in locally
 • Heterogenic internal advanced disease
echo pattern Less accurate in distinction of benign/low grade and
• Irregular border high grade neoplasm
 • Increased vascular flow
Guided biopsy
Assess nodes
Cost effective
Contrast enhanced Local extend of disease
computed tomography head Nodal status
and neck Cortical bone erosion
Magnetic resonant imaging Investigation of choice in
head and neck malignant lesions
 • Delineate soft tissue
 • Peri-neural spread
 • Bone marrow invasion
 • Recurrent lesion
PET CT Mild-moderate physiological uptake in salivary glands
Low sensitivity
37 Parotid Tumour 233

Table 37.2 Common histological subtypes of salivary gland tumours

Carcinoma ex
pleomorphic Squamous cell
Histology Mucoepidermoid Adenoid cystic Acinic cell adenoma carcinoma
Incidence Most common 2nd most common 8–14% 10% over a period Rare
30–35% 15–20% of 15 years
Most Parotid Minor salivary gland Parotid Parotid Parotid
common Site
Features Lymph nodal High perineural spread, Low grade Aggressive Most
spread common late recurrence, MC site aggressive
of metastasis-lung
Overall Low grade—80– OS-90% OS-97% OS-50% OS-40%
survival 90% OS
High grade—40–
50% OS
Prognosis Low grade—good Variable prognosis Best Poor prognosis Worst
prognosis depending on histologic prognosis prognosis
subtype

Table 37.3 Histological grades of salivary gland tumours

Malignant
Benign Low grade High grade
• Pleomorphic adenoma • Low grade mucoepidermoid • High grade mucoepidermoid carcinoma
• Warthin’s tumour • Low grade adenocarcinoma • Adenoid cystic carcinoma
• Oncocytoma • Acinic cell carcinoma • Mucinous adenocarcinoma
• Basal cell adenocarcinoma • Squamous cell carcinoma
• Sebaceous carcinoma • Undifferentiated carcinoma
• Carcinoma ex pleomorphic adenoma
• Salivary duct carcinoma

Table 37.4 AJCC staging salivary gland tumours 2017 Table 37.5 Lymph node involvement risk according to
histological subtype
T1—≤2 cm, without extra N—as in other head
parenchymal extension and neck cancers Lymph node involvement risk and histology
T2—>2 cm ≤ 4 cm, without M—as in other head High risk Intermediate risk Low risk
extra parenchymal extension and neck cancers Squamous cell Mucoepidermoid Acinic cell
T3—>4 cm, with or without STAGE I T1 N0 carcinoma carcinoma carcinoma
extra parenchymal extension M0 Undifferentiated Adenoid
T4a—moderately advanced carcinoma cystic
STAGE II T2 N0
disease (involvement of skin, Salivary duct carcinoma
M0
mandible, ear canal, facial carcinoma Carcinoma ex
STAGE III T3/N1 pleomorphic
nerve)
M0 adenoma
T4b—very advanced disease
STAGE IV T4a/
(involvement of skull base,
A N2 M0
pterygoid plate, carotid artery
encasement)
STAGE IV T4b/ 37.8.1 Early Stage
B N3
STAGE IV Any T, • Small primary (<4 cm)
C any N,
M1 • Low grade
234 V. R. Anjali

• Superficial tumour 37.10 Complication of Surgery

• Confined to superficial lobe.
• Facial nerve palsy-temporary/permanent
• Frey’s syndrome (gustatory sweating)
EARLY STAGE: Superficial parotidec- • Numbness over the ear (greater auricular
tomy with adequate margins and preserva- nerve)
tion of facial nerve • Hematoma
• Infection
• Flap necrosis
37.8.2 Locally Advanced • Parotid fistula.

• Tumour >4 cm
• High grade tumours 37.11 Radiotherapy
• T3/T4 disease
• Deep lobe involved 37.11.1 Indications
• If skin, muscle, bone, involved
• Adenoid cystic carcinoma requires explora- Indications for radiotherapy for parotid tumours
tion of nerve towards and through skull base are summarised in Table 37.6.
foramina to achieve tumour clearance Adjuvant radiotherapy is planned 4–6 weeks
• If pre-operatively facial nerve function is nor- after surgery.
mal and not infiltrated by the tumour try to
preserve facial nerve 37.11.1.1 Pre-treatment Assessment
• If facial nerve injury has occurred, micro-­ • Clinical examination
surgical nerve repair is considered • Dental evaluation
• Gross tumour encasement/infiltration of facial • Audiology
nerve/facial nerve palsy-nerve is sacrificed • Thyroid function test (neck is addressed)
and nerve grafting is done (sural nerve). • Written consent.

37.11.1.2 During Radiotherapy

• Weekly review
37.9 Neck Dissection • Assessment of acute toxicities and
management.

LOCALLY ADVANCED: Total Table 37.6 Indications for radiotherapy

Parotidectomy + LN dissection Adjuvant • High grade histology
radiotherapy • R1/R2 resection
• Lymph node positive/ECE
• Nerve involvement/perineural
• Low grade/superficial tumours—Observation invasion
• Recurrent tumour
only. Prophylactic neck dissection is not done • Tumour spillage
• High grade/locally advanced disease, clini- • T3/T4 tumour
cally/radiologically node negative—SOHND Pleomorphic • Positive or close margin,
• High grade/locally advanced disease, clini- adenoma revision surgery not possible
cally/radiologically node positive—MRND • Recurrent tumour
Radical • Medically inoperable
• Neck dissection provides details on extra cap-
• Unresectable primary
sular spread which is a poor prognostic Palliative • Pain
factor. radiotherapy • Bleeding, fungating mass
• Poor general condition
37 Parotid Tumour 235

37.12 EBRT Planning • Inferior—lower border of hyoid/cover scar

• Anterior—anterior border of clenched masse-
37.12.1 Patient Positioning ter/anterior to upper second molar
and Immobilisation • Posterior—mastoid process.

• Patient supine, neck extended, hands by side

• OR Right/left lateral position (depending on 37.13 S
 pecial Consideration in 2D
tumour laterality) and customised head rest in Planning
lateral position, neck extended
• Wire the scar site • Neck extended—to avoid exit dose to opposite
• Immobilisation with thermoplastic head and eye.
neck mask. • Half beam block technique also helps in
avoiding exit dose to contralateral eye.
• For electron field 1 cm extra margin is given
37.12.2 Target Volume from photon field in all direction to account
for constriction of higher isodose, and cover
• For disease confined to superficial lobe of PTV adequately.
parotid, early stage, low grade—Post-op • Bolus is used if skin is involved, close superfi-
tumour bed cial margin, capsule rupture, and tumour
• For locally advanced disease, high grade, spillage.
recurrent disease—Post op tumour bed + Neck • Photon beam provides a more homogeneous
Nodal region distribution but can increase dose to the con-
–– If nodes are surgically not addressed in tralateral parotid gland.
clinically N0 neck—Prophylactic/elective • Tissue heterogeneity (air cavity, external audi-
RT to ipsilateral neck nodal levels VII b, tory canal, bones) has to be taken into
1b, II, III, IV consideration.
–– If multiple nodes positive/multiple nodal
levels/ECE—Nodal irradiation from level
Ib to level V and VII b 37.14 3D Conformal/IMRT
• If adenoid cystic carcinoma, facial nerve is Planning
traced up to stylomastoid foramen.
CT Simulation From vertex to carina at 3 mm
Conventional 2D/Simulator-based planning slice thickness with intravenous contrast. Target
beam arrangement volume delineation guidelines is summarised in
Table 37.7.
• Superior—zygomatic arch

Table 37.7 Target volume delineation guidelines

Definitive RT Adjuvant RT Pleomorphic adenoma
• GTV 65—Gross • CTV 60—Post-­operative tumour bed+ high • GTV 60–66 Gy if gross
primary disease and risk nodal region residual disease (definitive)
gross nodal disease • CTV 54—Low risk nodal volume • CTV 50–55 Gy microscopic
• CTV 65—GTV • GTV 65—Macroscopic residual disease residual disease (post-op)
65 + 5 mm margin (if R2 resection) • No elective nodal irradiation
• CTV 60—CTV • CTV 65—GTV 66 + 5 mm
65 + 5 mm and nodal margin + microscopic residual disease
regions harbouring
gross nodes
• CTV 54—Elective
nodal regions
236 V. R. Anjali

Fig. 37.1 3D conformal planning in patient with carcinoma parotid

Contralateral neck is not treated electively. A Table 37.8 Relevant OARs for salivary gland tumours
conformal plan for carcinoma parotid is shown in Brainstem Dmax < 54 Gy, 1 cc < 60 Gy
Fig. 37.1. Spinal cord Dmax < 45 Gy, 0.03 cc < 48 Gy
Mandible Dmax < 70 Gy, 1 cc < 75 Gy
Oral cavity Dmean < 40 Gy
37.15 Beam Arrangements Contralateral parotid Dmean < 26 Gy
V 30 < 50%
Cochlea Dmean < 45Gy, V55 < 5%
1. Ipsilateral anterior and posterior oblique Submandibular gland Dmean < 45Gy
wedged fields with photon.
2. Ipsilateral anterior and posterior oblique
wedged fields and direct on field with photon.
3. Ipsilateral direct on field with photon electron 37.18 Neutron Therapy for Salivary
combination. Gland Tumours
4. Ipsilateral anterior and posterior oblique
wedged fields with photon and direct on field • Neutrons are densely ionizing particulate radi-
electrons. ation, with RBE >3.
• Less affected by hypoxia.
• Differential effect on various tissue.
37.16 Energy

• Photon—60Co, 4 to 6 MV 37.18.1 Indications

• Electron 12–16 MeV electrons
• Photon electron weightage is 1:4 (20% from • Unresectable gross disease
photon and 80% from electron). • Macroscopic gross residual disease
• Positive margin
• Recurrent disease.
37.17 O
 rgan at Risk and Dose
Constraints RTOG-MRC trial is the only phase III RCT
comparing neutron versus photon treatment for
Relevant OARs for salivary gland tumours are unresectable salivary gland tumours.
summarised in Table 37.8. 10-year follow-up data showed:
37 Parotid Tumour 237

• Improved locoregional disease control for 37.20 Follow-Up

neutrons (56% vs. 17%, p = 0.009)
• No improvement in overall survival First follow-up at 6–8 weeks after radiation
• Increased late grade 3 and 4 toxicity in neu- treatment.
tron treatment arm (impaired taste, temporal Every 3–4 monthly for first 2–3 years with
lobe necrosis, mucositis, pain, fibrosis). physical examination.
Every 6 monthly for next 2–3 years with phys-
ical examination.
37.19 Toxicity Then annually thereafter.

Common acute and chronic radiation toxicity in Source of Image Image has been taken from
salivary gland tumours are summarised in patient treated by author and consent has been
Table 37.9. taken.

Table 37.9 Common acute and chronic radiation toxic-

ity in salivary gland tumours
Acute Late
Skin changes Subcutaneous fibrosis
Mucositis Xerostomia
Fatigue Hearing loss
Dry mouth/thickened saliva Hypothyroidism
Dysgeusia Osteoradionecrosis
Otitis media Second malignancy
Hearing loss/ear ache
 Extremity Soft Tissue Sarcoma
38
Supriya Mallick and Goura K. Rath

Soft-tissue sarcomas are relatively uncommon 38.3 Examination

cancers accounting for less than 1% of all new
cancer cases. It includes a wide variety of histo- • Start with examination of the swelling
logical subtypes with variable chemosensitivity • Site, number
and radiosensitivity • Size
• Shape—spherical, oval, irregular
• Surface and skin over swelling—color, punc-
38.1 Risk Factors tum, inflammation, scars over swelling—
recurrence, dilated veins
Only few environmental risk factors have been • Borders/edge—well defined and regular
associated with the development of soft tissue • Consistency—soft, cystic, firm, hard
sarcoma: • Pulsations
• Palpation—tender/local rise of temperature—
• Chlorophenols in wood preservatives and phe- first to do in palpation
noxy herbicides • Fixity—skin and deeper structures—pinch
• Vinyl chloride increased risk of skin over swelling, move in direction and per-
angiosarcoma pendicular to fibers
• Human herpes virus 8 has been implicated in • Location—contraction of muscle
the development of Kaposi’s sarcoma –– Superficial remains mobile and become
prominent
–– Muscular—becomes immobile and fixed
38.2 History Taking –– Deep to muscle it becomes less palpable—
look at draining LN
• Swelling • Distal pressure effects in limb swelling
• Pain –– Distal wasting of muscles, movements and
• Change in color power of distal muscles, sensations—for
• Any history of trauma nerve compression
–– Distal pulsations—for arterial occlusion
S. Mallick (*) · G. K. Rath
–– Distal effects including edema—pressure
Department of Radiation Oncology, National Cancer effects and dilated veins—for venous
Institute-India (NCI-India), Jhajjar, Haryana, India occlusion

© Springer Nature Singapore Pte Ltd. 2020 239

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_38
240 S. Mallick and G. K. Rath

• Examination of lymph nodal region adjacent Table 38.1 AJCC08 TNM staging for extremity soft tis-
to the swelling sue sarcoma
–– Particularly in: RMS, angiosarcoma, clear T staging N staging Stage grouping
cell sarcoma T1—Size less than or N0—No • IA—T1 N0
equal to 5 cm N1—Yes M0 G1
• Abdominal examination—rarely hepatomeg-
T2—Size greater than M staging • IB—T2-4
aly or PA LN 5 cm < 10 cm N0 M0 G1
M0—
• Respiratory—lung metastasis is common T3—5–10 cm size None • II—T1N0
• CVS and CNS examination T4—Size more than M1—Yes M0 G2-3
15 cm • IIIA—T2
N0 M0 G2-3
• IIIB—T3-4
38.4 Differential Diagnosis N0 M0 G2-3
• IV—N1/M1
• Benign soft tissue mass
• Metastasis Table 38.2 French Federation of Cancer Centers
• Organized hematoma Sarcoma Group grading
Tumor Mitotic Tumor
differentiation count necrosis Grade
38.5 Workup 1 point: resembles 1 point: 0 points: Grade
normal adult 0–9 no 1: Total
mesenchymal mitoses necrosis 2–3
• Complete blood counts, RFT, LFT tissue 2 points: 1 point: points
• Biopsy: Direction should be parallel to the 2 points: histologic 10–19 <50% Grade
tumor, planned in such a way that the biopsy typing is certain mitoses necrosis 2: 4–5
3 points: synovial 3 points: 2 points: points
pathway and the scar can be safely removed
sarcoma, 20 or >50% Grade
by definitive surgery osteosarcoma, more necrosis 3: 6–8
• FNAC: Advised in few cases Ewing’s sarcoma, mitoses points
• MRI—local part, preferred except in retroper- etc.
itoneal and thoracic tumors where CT may be
sufficient 38.6.1 Patterns of Spread
• CECT Chest
• CT scan abdomen/pelvis—in patients with • Distant metastases—most common pattern of
myxoid/round cell liposarcoma and spread
leiomyosarcoma –– 10% have distant metastasis at
presentation
–– Lung is the most common site (70–80%) of
38.6 Staging: FIGO—Clinical spread of extremity sarcomas
Staging –– 80% of distant metastasis appear within
2 years
The factors that are taken into account for the • Lymph nodes—Less common than distant
TNM staging of soft tissue sarcomas are tumor metastasis
size, nodal status, grade (differentiation score), –– Only 5% of the patients with sarcomas
and metastasis. have positive lymph nodes at presentation
The AJCC 08 TNM staging for extremity soft –– Increased risk of lymph node metastasis
tissue sarcoma is summarized in Table 38.1. occurs in synovial sarcoma (14%), clear
Three-tier system is commonly used for grad- cell sarcoma (28%), angiosarcoma (23%),
ing. The FNCLCC (French) system is the pre- rhabdomyosarcoma (15%), and epithelioid
ferred grading system (Table 38.2). sarcoma (20%) (SCARE)
38 Extremity Soft Tissue Sarcoma 241

Risk of Distant Metastasis Depends on Grade, metastasis to either amputation vs. limb-­
tumor size, depth, and neurovascular bone sparing surgery + post-op chemo-RT [1]
involvement are independent predictors of • Radiation dose: 45–50 Gy followed by a
metastasis. boost to 60–70 Gy
• All patients received post-op
chemotherapy
38.6.2 Prognostic Factors • Outcome: Local failure limb-sparing 15%
vs. amputation 0% (p = 0.06)
38.6.2.1 I ncreased Risk for Local • 5-year DFS 71% vs. 78% (NS)
Recurrence • 5-year OS 83% vs. 88% (NS)
• Age >50 2. Surgery + post-op EBRT vs. surgery alone
• Recurrent disease • National Cancer Institute randomized
• Positive surgical margins patients with extremity to either limb-­
• Fibro sarcoma (including desmoid) sparing surgery followed by adjuvant radi-
• Malignant peripheral nerve tumors ation of 63 Gy with concurrent
chemotherapy or chemotherapy alone [2]
–– High grade: local recurrence chemo-RT
38.6.2.2 I ncreased Risk of Distant
Metastasis 0% vs. chemo 19%
–– 10-year OS 75% vs. 74% (NS)
• Size >5 cm
–– Low grade tumors: local recurrence RT
• High grade
4% vs. observation 33% (SS)
• Deep location
–– It reflected that adjuvant RT is highly
• Recurrent disease
effective in preventing local recurrence
• Leiomyosarcoma
3. Preoperative radiotherapy
Trials on pre-operative radiotherapy are
38.6.3 Treatment Overview summarized in Table 38.3
4. Preoperative RT vs. adjuvant RT
Surgery Historically amputation was the treat- O’Sullivan et al. from NCI Canada per-
ment of choice for extremity, then full compart- formed a randomized trial comparing pre-op
ment resection. At present en-bloc resection with RT vs. post-op RT which included 190
2 cm margin considered standard. Resection of patients. Primary endpoint was a major
skin and bone rarely required. wound complication. The pre-op RT group
received 50 Gy in 25 fractions with an option
38.6.3.1 Approaches of additional 16–20 Gy post-op boost. The
1. Amputation vs. limb-sparing surgery + post- post-op RT arm received a dose of 66–70 Gy.
­op chemo-RT Initial radiotherapy field included 5 cm proxi-
• National Cancer Institute randomized 43 mal/distal margin followed by the boost
patients with high-grade soft tissue sarco- which included 2 cm proximal/distal margin.
mas of the extremities, without distant Longitudinal strip of skin was untreated for at

Table 38.3 Trials on pre-operative radiotherapy

Trial Number Inclusion criteria Arms outcome
RTOG 95–14 [3] 64 Large (≥8 cm), high grade (G2-3) Neoadjuvant sequential 3-year LRF 18%
expected R0 resection chemo-RT 3-year DFS 57%
Toxicity-high
DeLaney et al. [4] 48 Large (≥8 cm), high grade (G2-3) Neoadjuvant sequential 5-year LC 92%
chemo-RT DFS 75%
OS 44%
242 S. Mallick and G. K. Rath

least half the course to avoid lymphedema. –– A 2D plan for extremity soft tissue sarcoma
Acute wound complications worsened after is shown in Fig. 38.1
pre-op RT but long-term extremity function –– Spare a strip of skin to avoid long-term
worsened after adjuvant RT [5]. lymphedema
Al-Absi et al. performed a meta-analysis of
5 studies with 1098 patients and found that Target volume according to VORTEX trial: 2
local recurrence was better in pre-op group cm cranio-caudal margin to GTV and minimum
(HR 0.6, SS). Survival pre-op group was 76% margin of 2 cm axially forms the CTV 1 cm mar-
vs. 67% in the post-op RT cohort [6]. gin for PTV, treatment in single phase (no Boost)
VORTEX trial was aimed to look into the fea-
sibility of reducing volume of tissue irradiated
38.7 Radiotherapy Planning Control arm (C): 50 Gy in 25 fractions to CTV1
for Soft Tissue Sarcoma (GTV + 5 cm cranio-caudally and 2 cm axially)
followed by 16 Gy in 8 fractions to CTV2
38.7.1 Indications for RT (GTV + 2 cm cranio-caudally and axially) or the
Experimental arm (R): 66 Gy in 33 fractions to
• RT for all tumors >5 cm and deep CTV2 alone. Two hundred sixteen patients were
• High grade even if ≤5 cm and deep randomized. The initial results show 5-year local
• If the surgical margin was less than 10 mm recurrence free survival (LRFS) rates were 86%
vs. 84%. 5-year overall survival was 72% vs. 67%.

38.7.2 PORT Dose Brachytherapy for Soft Tissue Sarcoma

Described in brachytherapy chapter.
• 66–70 Gy in 2 Gy per fraction depending on
margin status
38.8 Chemotherapy

38.7.3 Volumes 38.8.1 Adjuvant

• 2 Phase plan • The definite role of adjuvant chemotherapy is

–– Phase 1 CTV for limbs—operative bed not proven beyond doubt—Maybe considered
plus 5 cm longitudinal and 2 cm radial mar- for high-risk patients—high-grade tumors,
gin and includes the scar and biopsy sites deep, >5 cm tumor, after discussing with
–– Phase 2 CTV has only a 2 cm longitudinal patients potential toxicity and benefits
margin • Ifosfamide and adriamycin chemotherapy

Fig. 38.1 2D planning in a patient with limb sarcoma

38 Extremity Soft Tissue Sarcoma 243

38.8.2 Metastatic References

• Maybe useful in metastatic setting—histology 1. Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker
A, Brennan M, et al. The treatment of soft-tissue
driven chemotherapy
sarcomas of the extremities: prospective random-
• Relatively chemoresistant ized evaluations of (1) limb-sparing surgery plus
• If limited lung metastasis—may be consid- radiation therapy compared with amputation and
ered for resection (2) the role of adjuvant chemotherapy. Ann Surg.
1982;196:305–15.
• Single agent anthracyclines are preferred first
2. Yang JC, Chang AE, Baker AR, Sindelar WF,
line agent Danforth DN, Topalian SL, et al. Randomized pro-
• Only agent proved beneficial in combination spective study of the benefit of adjuvant radiation
with anthracycline-olaratumab (blocks therapy in the treatment of soft tissue sarcomas of the
extremity. J Clin Oncol. 1998;16:197–203.
PDGF-­ AA and PDGF-BB from binding
3. Kraybill WG, Harris J, Spiro IJ, Ettinger DS,
PDGFRα) has OS benefit DeLaney TF, Blum RH, et al. Phase II study of neo-
• Other agents adjuvant chemotherapy and radiation therapy in the
–– Myxoid/round cell liposarcoma—trabectedin management of high-risk, high-grade, soft tissue sar-
comas of the extremities and body wall: Radiation
–– Undifferentiated pleomorphic sarcomas—
Therapy Oncology Group Trial 9514. J Clin Oncol.
gemcitabine and docetaxel 2006;24(4):619–25.
–– Pazopanib—advanced non-adipocytic STS 4. DeLaney TF, Spiro IJ, Suit HD, Gebhardt MC,
–– Sunitinib—alveolar soft-part sarcomas and Hornicek FJ, Mankin HJ, Rosenberg AL, et al.
Neoadjuvant chemotherapy and radiotherapy for large
solitary fibrous tumor
extremity soft-tissue sarcomas. Int J Radiat Oncol
–– Angio sarcoma—taxanes may be beneficial Biol Phys. 2003;56(4):1117–27.
–– Eribulin—liposarcoma 5. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton
C, Chabot P, et al. Preoperative versus postoperative
radiotherapy in soft-tissue sarcoma of the limbs: a
randomised trial. Lancet. 2002;359:2235–41.
38.9 Follow-Up 6. Al-Absi E, Farrokhyar F, Sharma R, Whelan K,
Corbett T, Patel M, et al. A systematic review
• History and physical examination with X-ray and meta-analysis of oncologic outcomes of
pre- versus postoperative radiation in localized
or CT chest every 3–6 months in first 2–3 years
resectable soft-­ tissue sarcoma. Ann Surg Oncol.
• Then every 6 months till 5 years and then 2010;17(5):1367–74.
annually

Source of Image Image have been taken from

patient treated by author and consent have been
taken.
 Orbital Tumors
and Retinoblastoma 39
Kiran Turaka and Aruna Turaka

39.1 Introduction prevent metastasis, and increase survival. A mul-

tidisciplinary team of ophthalmologist, pediatric
Retinoblastoma (RB) is the most common pri- oncologist, radiation oncologist and pathologist
mary intraocular tumor in children. RB is more is important in management of these patients to
common in children in underdeveloped countries optimize outcomes.
and associated with higher mortality. The mortal- Treatment options for retinoblastoma include
ity in developed countries is lower due to early local treatment like cryotherapy, laser photoco-
diagnosis and latest treatment techniques. RB agulation [transpupillary thermal therapy
develops from cells that have cancer-­predisposing (TTT])], and plaque brachytherapy [1–5].
variants in both copies of RB1 gene: the first one Chemotherapy (intravenous, periocular, intra-
may be inherited and second one somatic (double vitreal, intra-arterial), external beam radiother-
hit hypothesis). It can be unilateral or bilateral apy, and proton beam irradiation also have a role
and in unilateral cases can be unifocal or multifo- in the management of RB. Usually a judicious
cal. The median age of diagnosis of bilateral reti- combination of these modalities is needed to
noblastoma is 15 months compared to 24 months optimize outcomes. Each of these treatments is
for unilateral cases. Bilateral and multifocal dis- associated with unique side effects. External
ease are more likely to be inherited RB. Hereditary beam radiotherapy (EBRT) and plaque brachy-
RB is inherited in an autosomal dominant pattern therapy are associated with radiation induced
and is also at a higher risk for non-ocular tumors complications and second malignancies. The
[1–5]. Patients with retinoblastoma, in addition side effects of systemic intravenous chemother-
to complete ocular examination, also need a sys- apy (IVC) include acute toxicity which includes
temic work-up to rule out intracranial lesions. hematological toxicity, nephrotoxicity, ototox-
Early diagnosis and treatment of RB is important icity, and long-term toxicities mainly blood dys-
in order to retain useful vision, reduce morbidity, crasias and infertility. Second malignant
neoplasms (SMN) are known to occur after
treatment with systemic chemotherapy and
K. Turaka (*) EBRT especially in hereditary RB than sporadic
Associated Retina Consultants Ltd,
RB cases. Pinealoblastoma can also occur in
Phoenix, AZ, USA
patients with RB (hereditary RB) and MRI of
A. Turaka
the brain may be needed.
Radiation Oncology, Paramount Oncology Group,
Dubuque, IA, USA Figure 39.1 summarizes common intraocular
e-mail: arunaturaka@gopog.com tumors among children and adults.

© Springer Nature Singapore Pte Ltd. 2020 245

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_39
246 K. Turaka and A. Turaka

Ocular tumors

Pediatric Adult

Intraocular tumors
Retinoblastoma
Orbital tumors Orbital tumors
Medulloepithelioma: iris and ciliary Intracular tumors
body Rhabdomyosarcoma Lymphoma
Choroidal nevus
Retinoblastoma Lacrimal gland tumors
Congenital Hypertrophy of Retinal Choroidal melanoma
Pigment Epithelium (CHRPE) Neuroblastoma Benign tumors: vascular tumors
Choroidal metastases
Lymphoma Eyelid and conjunctival tumors
Combine hamartoma of retina and RPE Vitreoretinal and choroidal lymphoma
Leukemia invading the orbit
Congenial melanocytosis Iris and ciliary body melanoma
Benign tumors

Fig. 39.1 Common intraocular tumors among children and adults

Choroidal melanoma is the most common unique advantage in that it shows clear visualiza-
intraocular lesion among adults. It can present as tion of the tumor through retina unlike FFA.
a small nevus and later grow to a melanoma Ultrasonogram (USG) is one of the most useful
involving the entire eyes. Choroidal melanoma is diagnostic tools especially in patients with amela-
also associated with systemic metastasis (most notic choroidal melanoma (very difficult to distin-
commonly liver) and can occur years after treat- guish from choroidal metastasis). Tumor vascularity,
ment is also one of the life threatening intraocular solidity, and choroidal excavation can be evaluated
tumors like RB [4, 6]. All patients need complete on USG, although there may be some overlapping
ocular examination including best corrected features for choroidal metastasis and melanoma.
visual acuity (VA), slit-lamp examination, bin- Choroidal melanoma can be plateau, dome or
ocular indirect ophthalmoscopy, fundus photog- mushroom shaped lesions ± RD on B scan USG.
raphy, fundus autofluorescence (AF), fundus Fine needle aspiration biopsy (FNAB) can be done
fluorescein angiography (FFA), indocyanine through transvitreal route with a 27 G needle and
green angiography (ICG-A), optical coherence has an accuracy of 90-98% in lesions of > 2 mm in
tomography (OCT), A and B scan ultrasonogra- thickness and is a highly accurate diagnostic test to
phy (USG), computerized tomography (CT) of confirm the histology of both anterior and posterior
the chest, magnetic resonance image (MRI) of segment tumors of the eye. FNAB has been shown
the abdomen, and liver function tests. Fundus to have a very high yield of up to 99% with few
autofluorescence (AF) can detect changes in the complications.
RPE and has advantage of being non-invasive. Computerized tomography (CT) scan of the
Hyperautofluorescence on AF is indicative of chest is helpful in detecting the metastatic lung
lipofuscin deposits in RPE cells, and hypoauto- tumors. MRI of the abdomen is helpful in diag-
fluoresce, whereas continuous pattern on AF sug- nosis and follow-up of metastatic lesions in the
gests normal function of RPE cells overlying the liver. Positron emission tomography (PET) scan,
tumor. AF is ideal to identify overlying tumor a newer evolving imaging modality is useful to
features and its margins. evaluate for distant metastases and to assess the
Heidelberg-Spectralis or Spectral-Domain tumor response to treatment.
OCT is useful for identifying the level of the The goal of treatment of intraocular tumors is
tumor, thickened choroid, presence of SRF, reti- to restore or stabilize the vision, improve quality
nal folds, and retinal thickening. Fundus fluores- of life, and improve survival. Various treatment
cein angiography (FFA) offers very little features options include observation, chemotherapy
to distinguish between choroidal melanoma, cho- (intravitreal anti-VEGF or systemic chemother-
roidal metastasis, and hemangioma. ICG-A has a apy), immunotherapy, radiotherapy (external
39 Orbital Tumors and Retinoblastoma 247

beam (EBRT), plaque brachytherapy and proton Genetic profiling via FNAB can be useful in
beam therapy (PBT)), laser therapy (transpupil- prognosticating patients with choroidal mela-
lary thermotherapy (TTT), photodynamic ­therapy noma. Loss-of-function of the BAP1 gene or
(PDT)), hormone therapy, and surgery (enucle- expression of a cancer-testis antigen PRAME
ation) [4, 6]. Treatment decision for choroidal (preferentially expressed antigen in melanoma) is
melanoma depends on the tumor size, depth, associated with the higher metastatic risk. Gain-­
extent, number of tumors, location and laterality of-­function of SF3B1 and EIF1AX genes is asso-
of tumors, visual acuity of status of the affected ciated with better prognosis. High-risk patients
eye, presence of other distant metastasis, age, and can be identified for clinical trials and may be
performance status of the patient. treated by targeted therapy for metastatic disease.
Plaque brachytherapy is useful for selective
lesions of the choroid (melanoma, metastasis, and
hemangioma) and provides rapid and effective 39.1.1 History (Fig. 39.2)
tumor control. Common radioisotopes used for
plaque brachytherapy includes Iodine (I-125), • Age—most important in diagnosis
Ruthenium (Ru106), and Palladium-103 [4]. • Pediatric—retinoblastoma, RMS
Plaque brachytherapy is usually delivered as in-­ • Adult—lymphomas, melanoma, metastasis
patient technique over a period of 3–7 days unlike • Presenting symptoms
EBRT (takes 3–4 weeks). Plaque brachytherapy • White reflex/squint—in retinoblastoma
can deliver radiation dose up to 60–70 Gy to the • Floaters—vitreous involvement
apex of the tumor. Unlike EBRT plaque brachy- • Proptosis—unilateral or bilateral
therapy delivers very little dose to neighboring • Pain
structures in the eye and orbit [6]. Common com- • Loss of vision/visual field loss—melanoma
plications after plaque brachytherapy of choroidal • Headache and vomiting—intracranial extension
melanoma include radiation papillopathy, reti- • B symptoms—lymphoma
nopathy and maculopathy, retinal vascular occlu- • Phthisis bulbi—common in neglected RB
sions, vitreous hemorrhage, chorioretinal atrophy, • History of known malignancy—possibly
dry eyes, cataract, and secondary glaucoma. metastasis

Clinical History and Physical Examination of Ocular tumors

Intraocular tumors Orbital tumors

Detailed Clinical history including family history, prior treatment & systemic illnesses Detailed Clinical history including family history, prior treatment & systemic illnesses

Visual acuity, IOP, Dilated fundus examination Visual acuity, IOP, Pupil check for RPAD

Fluorescein angiography Extraocular movements

Heidelberg-Spectralis optical Coherence Tomography/Visante OCT Hertels exophthalmometry

Fundus photography (Retcam or Panret photographs depending on age and location) Visual filed testing (Humphrey ro Goldman depending on location)

Fundus Autofluorescence Color vision testing (Ishihara plates)

A and B-scan Ultrasonography Fundus examination

Fine needle aspiration biopsy (diagnosis and genetic testing) B-scan Ultrasonography

Eletreoretinogram (ERG) and Visual evoked potential (VEP) testing

CT scan of Brain and orbits

Clinical diagnosis of the tumor based on the above tests (retinoblastoma, choroidal nevus, melanoma or
metastases etc ) MRI scans Brain and orbits
MRI Brain and orbits (part of metastatic work-up) Biopsy (excision or fine needle aspiration)
Ultrasonogram or MRI scans of the abdomen (check for liver metastasis in cases of choroidal melanoma) Ultrasonogram or MRI scans of the abdomen
Chest X-ray of CT scan of the chest (for lung metastases) Special scans: Octreotide scan, whole body PET scan
Whole body PET scan (distant metastases) Urinary VMA
Blood work-up (peripheral smear, CBC)
Blood work-up (especially LFT and KFT’s for suspected liver or lung metastases in choroidal
Bone marrow biopsy
melanoma)

Fig. 39.2 Clinical history and physical examination of intraocular and orbital tumors
248 K. Turaka and A. Turaka

• History of treatment for malignancy—possi- 39.2 Clinical Cases

ble second malignant neoplasm like sarcomas of Retinoblastoma
• Family history—important in retinoblastoma. and Choroidal Melanoma
Treated by Plaque
Brachytherapy and External
39.1.2 Clinical Examination (Fig. 39.2) Beam Radiation and Its
Complications
• Eye—external and dilated fundus
examination 39.2.1 C
 ase 1: Retinoblastoma
• Check visual acuity Treated Successfully by
• Check intraocular pressure (IOP) Iodine-125 Plaque
• Gonioscopy (iris and ciliary body nevus/mela- Brachytherapy
noma, medulloepitheliomas)
• Look for LN—parotid area and neck. A 6-month-old male child presented with leuko-
coria in both eyes (noticed by the parents). He
was a full-term born boy with no perinatal ill-
39.1.3 Investigations (Fig. 39.2) nesses. There was a family history of retinoblas-
toma (RB) with father being treated in the past
• Fundus photograph—color and red free for RB by chemotherapy and radiation therapy
(Retcam for RB, Panret for ciliary body (RT). On examination, visual acuity was not fix-
melanoma) ing or following the light with both eyes. There
• Fundus autofluorescence photographs was alternating esotropia (ET). On examination
• Optical coherence tomography (OCT) under anesthesia, anterior segment was unre-
• USG of the globe and the orbit (A and B markable in both eyes. Dilated fundus examina-
scans) tion revealed a creamy white tumor of 1.5 mm in
• CT scan orbit—presence of calcifications—RB basal diameter and 1 mm in thickness, located in
• MRI of the brain and orbits—more helpful the midperipheral retina [ICRB (International
than CT helps in optic nerve and intracranial Classification of Retinoblastoma) Group A,
involvement Reese-Ellsworth (RE) Group Ia] retinoblastoma
• Lumbar puncture/bone marrow involvement in the right eye. There was a 9.5 mm basal diam-
in selected cases (primary vitreoretinal or eter and 3.9 mm thickness white tumor located at
uveal lymphoma) the optic disc, ICRB Group C, RE Group IIa, in
• Chest X-ray—to rule lung lesions (in case of the left eye (Fig. 39.3a). There were no subretinal
choroidal metastases for primary lung lesions or vitreous seeds in either eye. Magnetic reso-
or choroidal melanoma with distant metasta- nance imaging (MRI scan) of the brain was
ses to the lung) unremarkable with no intracranial lesions.
­
• USG abdomen—in choroidal melanoma to Intraocular pressure was 15 mmHg in the right
rule out liver metastasis eye and 18 mmHg in the left eye. Patient was
• CT scan of the chest and MRI scan of the treated with 6 cycles of systemic intravenous
abdomen as part of metastatic work-up chemotherapy with vincristine, etoposide, and
• Blood work-up (liver function tests, kidney carboplatin [chemoreduction (CRD)]. Additional
function tests as part of choroidal melanoma treatment was done by consolidated cryotherapy
metastatic work-up) to the local intraocular retinoblastoma in both
• Whole body PET scan (to check for distant eyes which regressed the RB (Fig. 39.3b). After
metastasis and treatment follow-up). 5 months of chemotherapy, the right eye was
39 Orbital Tumors and Retinoblastoma 249

a c

b d

Fig. 39.3 Fundus photograph of the left eye (a) showing RB tumor seen at the optic nerve (c), that was further
ICRB Group C retinoblastoma located at the optic nerve treated by I-125 plaque radiotherapy (40 Gy). At 5-year
that regressed (b) completely after treatment with 6 cycles follow-up, no signs of recurrence or radiation complica-
of CRD. Ten months following chemoreduction, recurrent tions (d) noted with complete regression of RB

quiet with completely regressed retinoblastoma, ocular recurrence of RB in either eye. Visual acu-
whereas in the left eye there was a recurrence of ity was 20/60 in right eye and hand motion in the
the tumor that was treated by transpupillary ther- left eye. There were no radiation related compli-
motherapy. At 10 months of follow-up, right eye cations or tumor recurrence noted in the left eye
was stable with no tumor recurrence or subretinal (Fig. 39.3d).
or vitreous seed recurrence. However, in the left
eye there was a new tumor noted superior to the
initial retinoblastoma measuring 8 mm in basal 39.2.2 C
 ase 2: Retinoblastoma
diameter and 3.5 mm in thickness (Fig. 39.3c) Treated by Iodine-125 Plaque
with no recurrence of subretinal or vitreous seeds Brachytherapy and EBRT
(ICRB Group C). The new retinoblastoma tumor
in the left eye was treated with plaque brachy- A 4-month African-American male was referred
therapy (Iodine-125 (125I), 40 Gy over 3–5 days). when leukocoria was noted by pediatrician in
After 5 years of follow-up, the patient was alive both eyes. On examination, there was a large
with no systemic metastases and no local intra- white tumor at the optic nerve measuring 10 mm
250 K. Turaka and A. Turaka

in basal dimension and 6 mm in thickness with a new tumor was seen measuring 2 × 2 mm tumor
surrounding subretinal seeds, subretinal fluid, located in the midperipheral retina with few sub-
and vitreous seeds (RE-Group Vb, ICRB Group retinal seeds but no vitreous seed recurrence in
C) in the right eye. There was 14 mm basal diam- the right eye. This new RB in the right eye was
eter creamy white tumor near the optic nerve treated by plaque radiotherapy (125I plaque
with a thickness of 9 mm in the left eye (RE-Group brachytherapy, 40 Gy over 4 days). However, in
VIb, ICRB Group D) with multiple subretinal the left eye along with tumor recurrence, there
seeds, vitreous seeds, and retinal detachment were multiple vitreous seed recurrence and a new
(Fig. 39.4a). MRI scan of the brain revealed a tumor measuring 4 × 3 mm in the mid peripheral
pinealoblastoma. He was diagnosed with trilat- retina were noted (Fig. 39.4c). The new RB and
eral retinoblastoma and treated by chemoreduc- the recurrent tumors in the left eye were treated
tion with 6 cycles of vincristine, etoposide, and by external beam radiotherapy (EBRT, 40 Gy, 10
carboplatin. Patient was followed up every month fractions). After 1 year of treatment, there was no
by examination under anesthesia and after recurrence of retinoblastoma in either eye
2 months of follow-up, there was subretinal seed (Fig. 39.4d) with stable pinealoblastoma, but
recurrence that was treated by cryotherapy in after two and half years of treatment he died with
both eyes (Fig.39.4b). At 3 months of follow-up, multiple systemic metastases.

a c

b d

Fig. 39.4 Fundus photograph of the left eye (a) showing that was treated by EBRT (4000 cGy), and at 1 years of
ICRB Group D retinoblastoma that was treated with 6 follow-up after EBRT, there is no recurrence of the RB
cycles of CRD. Regressed RB after treatment (b), but tumor (d) in the left eye
there was a tumor recurrence at 3 months of follow-up (c),
39 Orbital Tumors and Retinoblastoma 251

39.2.3 C
 ase 3: Choroidal Melanoma right eye was 20/25 and 20/20 in the left eye and
Treated Successfully by intraocular pressure was 19 mmHg in both eyes.
Iodine-125 Plaque The choroidal melanoma in the right eye has
Brachytherapy regressed to 1.7 mm (Fig. 39.5c, d) with no radia-
tion related side effects. Systemic work-up by
A 50-year-old male was referred with a diagnosis liver function tests, ultrasound abdomen, and
of pigmented spot in the right eye. Visual acuity chest X-rays revealed no evidence of metastasis.
was 20/20 in each eye. Intraocular pressure was
15 mmHg in both eyes. Slit lamp biomicroscopic
examination was unremarkable in the right eye 39.2.4 C
 ase 4: Second Malignant
and there was a small pigmented lesion on the iris Neoplasms as a Complication
of the left eye. Dilated fundus examination of EBRT After Treatment
revealed a pigmented choroidal lesion measuring of Retinoblastoma
8 × 6 × 3 mm (Fig. 39.5a, b) with overlying orange
pigment and additional subretinal fluid. Patient An 8-month-old child presented with bilateral
was diagnosed with choroidal melanoma and was leukocoria to the pediatric ophthalmology depart-
treated with Iodine-125 plaque radiotherapy. ment. Upon examination under anesthesia, there
After 4 months of treatment, visual acuity in the were large creamy white tumors in both eyes

a c

b d

Fig. 39.5 Color fundus photograph of the right eye of 3 mm on B-scan ultrasonogram (b). After 4 months of
showing a pigmented melanoma inferior to the optic nerve plaque radiotherapy, the choroidal melanoma (c) regressed
measuring 8 × 6 mm in basal diameter (a) with a thickness to 1.7 mm in thickness (d)
252 K. Turaka and A. Turaka

(measuring more than 15 mm in basal dimension Computerized tomography (CT) scan of the orbits
and 10 mm in thickness) with multiple subretinal revealed an inferotemporal orbital mass on the
and vitreous seeds. He was diagnosed with ICRB right side (Fig. 39.6b). Biopsy from the lesion
Group E RB in the right eye (Fig. 39.6a) and showed epithelioid cells that stained positive with
Group D RB in the left eye. He was treated with 6 Melan A, vimentin, and S100 proteins suggestive
cycles of vincristine, etoposide, and carboplatin of invasive malignant melanoma. He was treated
(VEC). Enucleation of the right eye was per- by right orbitotomy and further chemotherapy. At
formed due to advanced RB, whereas tumor con- seven years of follow-up, the right socket was free
solidation therapy with cryotherapy was done for of tumor, whereas in the left temporal area there
the left eye RB followed by EBRT (44 Gy). After was a mass. Further studies by MRI scanning
3 years of treatment, left eye was stable with no revealed a large mass in the temporal fossa on the
recurrence of RB, whereas in the right socket, left side (Fig. 39.6c). Biopsy revealed rhabdo-
there was a small non-pigmented lesion. myosarcoma (RMS) that was treated by excision,

a c

d
b

Fig. 39.6 Retcam fundus photograph showing Group E melanoma). At 7 years of follow-up, no tumor recurrence
retinoblastoma in the right eye (a) treated by enucleation in the right orbit, but there was a homogeneous lesion in
and CRD plus EBRT to the left eye for Group D RB. After the left temporal fossa (c) which was treated by excision
3 years of follow-up, there was an amelanotic lesion with (rhabdomyosarcoma), further chemotherapy and EBRT
well-defined margins on the CT scan in the inferotempo- and at 9 years of follow-up no tumor recurrence seen on
ral right orbit (b), and was treated by excision (malignant either side (d)
39 Orbital Tumors and Retinoblastoma 253

6 more cycles of chemotherapy, and additional 2. Skalet AH, Gombos DS, Gallie BL, et al. Screening
EBRT (50 Gy). MRI scan of the orbits and brain children at risk for retinoblastoma: consensus report
from the American Association of Ophthalmic
after 9 years of initial treatment, he was alive and Oncologists and Pathologists. Ophthalmology.
active with no tumor recurrence in right socket or 2018;125(3):453–8.
left temporal fossa (Fig. 39.6d) and there was no 3. Bornfeld N, Biewald E, Bauer S, et al. The interdisci-
evidence of systemic metastases. plinary diagnosis and treatment of intraocular tumors.
Dtsch Arztebl Int. 2018;115(7):106–11.
Consent of the patients has been taken for pre- 4. American Brachytherapy Society - Ophthalmic
senting the case scenarios. The patients were not Oncology Task Force. Electronic address: paulfin-
a part of trial and was treated as per standard pro- ger@eyecancer.com; ABS – OOTF Committee.
tocol of the hospital. The American Brachytherapy Society consen-
sus ­guidelines for plaque brachytherapy of uveal
melanoma and retinoblastoma. Brachytherapy.
2014;13(1):1–14.
5. Francis JH, Barker CA, Wolden SL, et al. Salvage/
References adjuvant brachytherapy after ophthalmic artery che-
mosurgery for intraocular retinoblastoma. Int J Radiat
1. Francis JH, Roosipu N, Levin AM, et al. Current treat- Oncol Biol Phys. 2013;87(3):517–23.
ment of bilateral retinoblastoma: the impact of intra- 6. Le BHA, Kim JW, Deng H, et al. Outcomes of cho-
arterial and intravitreous chemotherapy. Neoplasia. roidal melanomas treated with eye physics plaques: a
2018;20(8):757–63. 25-year review. Brachytherapy. 2018;17(6):981–9.
 Carcinoma Rectum
40
Bhanu Prasad Venkatesulu

40.1 History Taking FAP-Familial adenomatous polyposis, Peutz–

Jeghers syndrome, MYH-associated
• Bleeding PR polyposis
• Discharge PR-mucoid, sometimes mixed with • History of adenomatous polyps
blood • H/o radiation to pelvis.
• Alteration in bowel habits—constipation, con-
stipation alternating with diarrhea, change in
caliber of stools, feeling of incomplete evacu- 40.3 Examination
ation of stools (low rectal cancer)
• Rectal tenesmus—sensation of needing to • Per rectal examination—Sims position (left
pass stool, accompanied by pain, cramping, lateral position)—Start with inspection of
and straining perianal region—Perianal tags, fissure, fistula.
• Incontinence—sphincter involvement Palpation—Massage the external sphincter
• Anemia—in case of occult bleeding and slowly do PR comment on sphincter tone,
• Back pain—advanced stages with nerve nature of growth-proliferative or ulcer prolif-
involvement erative, how circumferential, extent of the
• Colicky abdominal pain—partial obstruction tumor from anal verge, able to get above the
• Weight loss. tumor or not, describe in terms of clockwise
position, perirectal, pararectal mobility, blood
and fecal soiling of gloves
40.2 Other Relevant History • Examination of inguinal area—LN
• Abdominal examination—rarely hepatomeg-
• Non-vegetarian diet with consumption of pro- aly or para-aortic lymph node
cessed red meat • Respiratory, CVS, supraclavicular lymph
• Obesity, smoking, alcoholism node.
• Inflammatory bowel disease—ulcerative coli-
tis, Crohn’s disease
• Family history of rectal cancer—inherited 40.4 Differential Diagnosis
conditions like HNPCC-Lynch syndrome,
• Ca Rectum
B. P. Venkatesulu (*) • Hemorrhoids
MD Anderson Cancer Center, Houston, TX, USA • Rectal polyp

© Springer Nature Singapore Pte Ltd. 2020 255

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_40
256 B. P. Venkatesulu

40.5 Work-Up Table 40.1 Stage-wise survival in rectal cancer

Rectal cancer staging 5-year survival (%)
• Complete blood counts, RFT, LFT,S.CEA Stage 1 T1-2N0M0 90
• Colonoscopy with biopsy—to rule out other Stage 2A T3N0M0 60–85
   2B T4N0M0
synchronous lesions
Stage 3A T1-2N1M0 55–60
• MRI pelvis with CT of chest and abdomen(or    B T3-4N1M0 35–42
CECT chest, abdomen, and pelvis)    C T1-4N2M0 25–27
• Endorectal ultrasound in lower rectal cancer Stage 4 T1-4N0-2M1 5–7
(non-stenotic lesions).

Table 40.2 Treatment outline in rectal cancer

40.6  taging and Survival Stage
S Rectal cancer treatment
Wise Low riska,b cT1-2N0 Total
cT3N0-≤5 mm mesorectal
extramural invasion, excision
• Table 40.1 summarizes AJCC staging of rectal distance to mesorectal
cancers and survival. fascia >1 mm
Intermediate cT1-3N1 5∗5 Gy
risk cT3N0->5 mm preoperative
extramural invasion, radiotherapy
40.7  taging: AJCC 8th Edition
S distance to mesorectal followed by
2017—Points to Remember fascia >1 mm TME
[1] High risk –any cT+N2 Neoadjuvant
–any cT+ suspicious chemoradiation
extramesorectal nodes followed by
• Minimum of 12 lymph nodes needed for ade-
–cT3 distance to surgery
quate nodal staging mesorectal fascia
• N1c—indicates tumor deposits that lack asso- ≤1 mm
ciated lymph node tissue, vascular or neural –cT4
structures and is found within the lymphatic a
Indications for transanal endoscopic microsurgery
drainage area of the primary carcinoma (TEM)-<3 cm in size,<30% circumference of bowel,
mobile, nonfixed, within 8 cm of anal verge, tumor limited
• N1c even in the absence of nodal metastases is to submucosa (T1), N0, no LVSI, no PNI, well to moder-
stage III. ately differentiated
b
In lower rectal cancer, the rectum lacks peritoneum, sur-
gical plane of dissection is difficult and distal resected
margin should be at least 2 cm for sphincter preservation.
40.8 Treatment Outline In these scenarios, even in low risk rectal cancer, neoadju-
vant therapy followed by surgery is recommended if
Treatment outline in rectal cancer is summarized patient is not suitable for TEM
in Table 40.2.

40.10 Radiotherapy Planning

40.9 Treatment Scheme
40.10.1 EBRT Planning
50.4 Gy in 28 daily fractions of 1.8 Gy in 51/2
weeks with concurrent Capecitabine or 25 Gy in 2D Planning—4 Field Technique Borders
5 fractions over 5 days if short course followed
by surgery in 4–6 weeks followed by adjuvant • Superior border—between L5 and S1
chemotherapy. vertebrae
40 Carcinoma Rectum 257

• Inferior border—3 cm below the lower extent • MRI fusion preferable to aid in delineation,
of the clinical tumor or the inferior edge of GTV as per MRI and clinical examination
obturator foramina whichever is the most findings.
inferior
• Lateral borders—1.5–2 cm outside the bony
pelvic side wall 40.10.3 Palliative RT
• Posterior border—1.5 cm behind the anterior
bony sacral margin • 25 Gy in 5 fractions in metastatic cancer
• Anterior border—posterior margin of the patients to prevent bleeding or reduce chances
symphysis pubis, anterior margin of the sym- of luminal obstruction.
physis pubis (if to include external iliac LN).

40.11 Chemotherapy
40.10.2 Conformal Radiotherapy
(Fig. 40.1) • Capecitabine—850 mg/m2 twice daily with
radiation with weekends off and with food or
• The patient needs to fast for 4 h before CT within 30 min after eating a meal.
simulation, empty bladder, and drink 100 mL
of water 30 min before CT simulation. Patient
is placed in prone position with a belly board 40.12 Follow-Up
to displace the small bowel, placing a rectal
marker and using rectal contrast helps to • Clinic visit 4–6 weeks after treatment
delineate the tumor and placing a radiopaque • Two CT scans of chest, abdomen, and pelvis
marker along the perineum helps to block the in the first 3 years and regular blood tests
skin and reduce skin toxicity • Colonoscopy 1 year after surgery and if colo-
• CTVA: internal iliac, pre-sacral, perirectal. noscopy is normal another in 5 years.
• CTVB: external iliac nodal region
• CTVC: inguinal nodal region
40.13 Recurrence

• Recurrence post-surgery alone—RT

• Recurrence post-RT—Surgery/can try reirra-
diation if >1 year, reirradiation dose is 39 Gy
in 26 fractions twice a day over 13 days.

Source of Image Image has been taken from

patient treated by author and consent has been
taken.

Fig. 40.1 3D conformal radiotherapy plan for rectal

cancer Reference
• CTVA would be the only volume to receive
1. https://en.wikibooks.org/wiki/Radiation_Oncology/
elective radiation. Extension into GU
Rectum/Staging.
structures—add CTVB, extension to the peri-
anal skin—add CTVC
 Carcinoma Anal Canal
41
Bhanu Prasad Venkatesulu

41.1 History Taking [1] and slowly do PR comment on sphincter tone,

nature of growth-proliferative or ulcer prolif-
• Perianal pain or bleeding erative, how circumferential, extent of the
• Incontinence of solid or liquid stool or gas tumor from anal verge, able to get above the
• Sensation of anal mass or prolapse tumor or not, describe in terms of clockwise
• Local wetness and irritation position, perirectal, pararectal mobility, blood
• Weight loss. and fecal soiling of gloves
• Examination of inguinal Area—LN
• Abdominal examination—Rarely hepatomeg-
41.2 Other Relevant History aly or para-aortic lymph node
• Respiratory, CVS.
• H/o chronic hemorrhoids
• Perianal skin tags or warts
• Anal fissure, anal fistula 41.4 Differential Diagnosis
• HPV—anoreceptive intercourse or drip down
effect from other HPV infected secretions • Ca rectum
• HIV or post-organ transplant- • Hemorrhoids
immunosuppression. • Rectal prolapse
• Condyloma.

41.3 Examination
41.5 Work-Up
• Per rectal examination—SIM position (left
lateral position)—Start with inspection of • Anoscopy and rigid proctoscopy to determine
perianal region—Perianal tags, fissure, fistula. the size of the primary lesion and the extent of
Palpation—Massage the external sphincter the spread of disease with biopsy
• If inguinal lymph nodes are enlarged, core
needle biopsy of LN should be done
B. P. Venkatesulu (*) • Complete blood counts, RFT, LFT
MD Anderson Cancer Center, Houston, TX, USA • CECT chest, abdomen, and pelvis.

© Springer Nature Singapore Pte Ltd. 2020 259

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_41
260 B. P. Venkatesulu

41.6  taging: AJCC 8th Edition

S Table 41.1 Stage wise survival in patients with anal
cancer
2017
Stage 5 year overall Local
grouping survival (%) control (%)
• T1—tumor size ≤2 cm
I—T1 N0 90 13
• T2—tumor size >2 but less than 5 cm
IIA—T2 N0 82 17
• T3—tumor size more than 5 cm IIB—T3 N0 74 18
• T4—invades adjacent organ, e.g., vagina, ure- IIIA—T1-2 70 26
thra, bladder. N1 57 44
IIIB—T4 N0 57, 42 44, 60
IIIC—T3 N1,
Regional lymph nodes: mesorectal, inguinal, T4 N1
superior rectal, external iliac, and internal iliac IV—M1 Median PFS 4 months with median
OS 11.5 months
• N1a—inguinal, mesorectal, or internal iliac
lymph nodes
Table 41.2 Stage wise treatment in patients with anal
• N1b—external iliac nodes cancer
• N1c—external iliac nodes + N1a
T1N0M0b, c CTRT with 45–50.4 Gy in 28
• M1—presence of distant metastasis. mitomycin-C fractions to the
and 5-FU primary
T2 onwards CTRT with 54–59.4 Gy to the
41.7  taging and Survival Stage
S node mitomycin-C primary and 45 Gy
negative and 5-FU to the uninvolved
Wise nodes
Node CTRT with 54–59.4 Gy to the
Stage wise survival in patients with anal cancer is positive mitomycin-C primary and 50 Gy
summarized in Table 41.1. disease, and 5-FU to the uninvolved
<3 cma nodes
Node CTRT with 54–59.4 Gy to the
positive mitomycin-C primary and 54 Gy
41.8 Treatment Outline [2] disease, and 5-FU to the uninvolved
>3 cma nodes
Treatment outline in anal cancer is summarized a
Perirectal, inguinal, internal, external iliac groups
in Table 41.2. of lymph nodes are included in the radiation portal
b
Local excision is an option for patients with T1 tumors
less than 1 cm in size
c
Elderly T1N0MO can give 5-FU alone with RT
41.9 Radiotherapy Planning
• Posterior border—1.5 cm behind the anterior
41.9.1 EBRT Planning (Fig. 41.1) bony sacral margin
• Anterior border—Anterior margin of the sym-
2D Planning—4 field technique borders physis pubis.
• Inguinal fields: Medial border abuts the lateral
• Superior border—between L5 and S1 border of the pelvic fields
vertebrae –– Lateral border: vertical tangent along the
• Inferior border—3 cm below the lower extent lateral border of shaft of femur
of the clinical tumor or 3 cm below the anal –– Superior border: horizontal tangent along
verge the head of femur
• Lateral borders—1.5–2 cm outside the bony –– Inferior border: 3 cm below the lower bor-
pelvic side wall der of obturator foramen.
41 Carcinoma Anal Canal 261

Inguinal Field Pelvic Field

Fig. 41.1 2D planning in patient with anal cancer

41.10 Conformal Radiotherapy 41.11 Palliative RT

• The “frog legged” supine position avoids • 25 Gy in 5 fractions in metastatic cancer

radiation dermatitis and allows auto-bolus of patients to prevent bleeding or reduce chances
the anal region. Custom immobilization of luminal obstruction.
devices such as vac-loc cradles may be used
to aid in reproducibility with rectal tube and
contrast 41.12 Chemotherapy
• CTVA: internal iliac, pre-sacral, perirectal.
• CTVB: external iliac nodal region Wayne State or Nigro regimen—infusional FU
• CTVC: inguinal nodal region 1000 mg/m2 on days 1–4 and 29–32 (plus mito-
• Anal canal contours should have CTVA, mycin 10–15 mg/m2 on day 1 concurrent with
CTVB, and CTVC. RT).
• MRI fusion preferable to aid in delineation,
GTV as per MRI, and clinical examination
findings 41.13 Follow-Up

Figure 41.2 shows contouring and IMRT plan • Patients in complete remission at 8 weeks
in patient with anal cancer. should be evaluated every 3–6 months for a
262 B. P. Venkatesulu

Fig. 41.2 Contouring and IMRT planning in patient with anal cancer

period of 2 years, and 6–12 monthly until Source of image Images have been taken from
5 years, with clinical examination including patients treated by author and consent has been
DRE and palpation of the inguinal lymph taken.
nodes.
• Digital examination at 11, 18, and 26 weeks
from the start of the treatment, ­abdominopelvic References
CT at week 26, confirm residual or recurrent
disease by biopsy. 1. https://en.wikibooks.org/wiki/Radiation_Oncology/
Anal_canal/Overview.
2. Mallick S, Benson R, Julka PK, Rath GK. Shifting
paradigm in the management of anal canal carcinoma.
41.14 Recurrence J Gastrointest Cancer. 2015;46(1):1–4.

• Recurrence—surgery(APR)
 Skin Cancer
42
Nikhil P. Joshi and Martin C. Tom

42.1 History Taking 42.3 Examination

• Skin lesion—location, onset, duration, pro- • General nutritional status, performance status
gression (especially from previous lesions)
• Bleeding Inspection
• Pain 1. Inspect the index lesion for size, color, bor-
• Tingling, numbness, or other neurologic defi- ders (regular/irregular), bleeding, satellite
cits (typically cranial nerve palsies from head nodules
and neck skin cancers) 2. Whole body examination to rule out other
• Adjacent swelling or associated lesions lesions.
• Lymph node swelling in the adjacent lym-
phatic bed. Palpation
1. Palpate the lesion for tenderness, indura-
tion, depth, and fixity to underlying
42.2 Other Relevant History structures
2. Palpate the relevant nodal drainage areas,
• H/o previous skin cancers especially the parotid gland, occipital, sub-­
• H/o sun exposure occipital nodes, and spinal accessory nodes
• H/o immunosuppression (organ transplant, for head and neck skin cancers
low grade lymphomas, HIV, etc.) [1, 2]
• H/o occupational exposure (arsenic)
• H/o field treatment for skin cancer 42.3.1 Examination of the CNS
(5-­fluorouracil cream, blue light therapy or
radiation therapy) • Particular attention must be given to examina-
• H/o chronic irritation (chronic ulcer in dia- tion of cranial nerves depending upon the
betic patients, chronic osteomyelitis, long extent of disease especially if neurologic
standing sinus/fistula, burn ulcer, etc.) symptoms are noted.
• Relevant medical and surgical co-morbidities.

N. P. Joshi (*) · M. C. Tom

Cleveland Clinic Foundation, Cleveland, OH, USA
e-mail: joshin@ccf.org

© Springer Nature Singapore Pte Ltd. 2020 263

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_42
264 N. P. Joshi and M. C. Tom

42.3.2 Systemic Examination • Bimodality treatment is favored with surgery

followed by adjuvant radiation (with or
• Relevant systemic examination should be without chemotherapy) when possible (an
done in addition to general ear, nose, and exception is AJCC 8th edition T3 BCC
throat examination for head and neck skin which may be treated with surgery alone/
cancers radiation alone)
• Complete skin examination for other skin • Unresectable primaries maybe treated with
cancers. definitive radiation (with or without chemo-
therapy or cetuximab)
• Indications for adjuvant treatment with radi-
42.4 Work-Up ation or chemoradiation are controversial
and being explored in prospective clinical
• CBC, RFT, LFT trials
• Punch biopsy of the primary skin lesion • Locally advanced BCCs—usually treated
• Core biopsy of any enlarged lymph node with surgery, reconstruction, and adjuvant
• Contrast enhanced CT scan of the relevant radiation especially when recurrent (select
anatomical site cases may be treated with surgery alone)
• Contrast enhanced MRI of the skull base to • Periorbital BCCs with significant orbital/
assess extent of neurotropic head and neck globe involvement—usually treated with
skin cancers exenteration, reconstruction, and adjuvant
• Whole body PET CT radiation especially when recurrent; vismo-
• Comprehensive dental evaluation for head and degib is being explored in the neoadjuvant set-
neck skin cancers (extractions must be com- ting and may be used for patients refusing
pleted 14–21 days before radiation) surgery/radiation
• Comprehensive audiometry if cisplatin will be • Unresectable BCCs—usually treated with
used. definitive radiation; vismodegib may be used
for patients refusing radiation or for multiple
BCCs (basal cell nevus syndrome)
42.5 Staging
Recurrent non-metastatic disease amenable to
AJCC staging cutaneous squamous cell carci- curative therapy
noma of the head and neck is summarized in
Table 42.1 and Brigham and Women’s Hospital • Surgical salvage followed by aggressive adju-
(BWH) staging system for cutaneous squamous vant radiation (or re-irradiation) with or with-
cell carcinoma is summarized in Table 42.2. out chemotherapy

Incurable skin cancer (metastatic or non-­

42.6 Treatment Outline metastatic) not amenable to curative therapy

Early skin cancer (AJCC 8th edition SCC or • Palliative immunotherapy with cemiplimab [5]
BCC: T1-2, N0 or BWH SCC: T1-T2a stage) • Palliative radiation (conventional, Quad Shot,
or stereotactic body radiotherapy for select
• Unimodality treatment is favored with either cases)
radiation or surgery alone • Palliative surgery in select cases.

Locally advanced skin cancer (AJCC 8th edi-

tion SCC or BCC: T3-4, node positive, recurrent
cases or BWH SCC: T2b-T3)
42 Skin Cancer 265

Table 42.1 AJCC staging for cutaneous squamous cell carcinoma of the head and neck
Staging: AJCC 8th ed., 2017 cutaneous squamous cell carcinoma of the head and neck [3]
TX Primary tumor cannot be cNX Regional lymph nodes pNX Regional lymph nodes cannot
assessed cannot be assessed be assessed
Tis Carcinoma in situ cN0 No regional lymph node pN0 No regional lymph node
metastasis metastasis
T1 ≤2 cm in greatest cN1 Metastasis in a single pN1 Metastasis in a single
dimension ipsilateral lymph node, ipsilateral lymph node, ≤3 cm
≤3 cm in greatest dimension in greatest dimension and
and ENE(–) ENE(–)
T2 >2 but not >4 cm in cN2a Metastasis in a single pN2a Metastasis in a single ipsilateral
greatest dimension ipsilateral node >3 cm but lymph node, ≤3 cm in greatest
<6 cm in greatest dimension dimension and ENE(+);
and ENE(–) Or a single ipsilateral node
>3 cm but not >6 cm in
greatest dimension and ENE(–)
T3 >4 cm in greatest cN2b Metastases in multiple pN2b Metastases in multiple
dimension or minor bone ipsilateral nodes, none >6 cm ipsilateral nodes, none >6 cm
erosion or perineural in greatest dimension and in greatest dimension and
invasion or deep invasiona ENE(–) ENE(–)
T4a Gross cortical bone/ cN2c Metastases in bilateral or pN2c Metastases in bilateral or
marrow invasion contralateral lymph nodes, contralateral lymph node(s),
none >6 cm in greatest none >6 cm in greatest
dimension and ENE(–) dimension and ENE(–)
T4b Skull base invasion and/or cN3a Metastasis in a lymph node pN3a Metastasis in a lymph node
skull base foramen >6 cm in greatest dimension >6 cm in greatest dimension
involvement and ENE(–) and ENE(–)
M1 Distant metastasis cN3b Metastasis in any node(s) pN3b Metastasis in a single ipsilateral
and ENE(+) node >3 cm in greatest
dimension and ENE(+);
Or multiple ipsilateral,
contralateral, or bilateral
nodes, any with ENE(+);
Or a single contralateral node
of any size and ENE(+)
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3 N0 M0
T1-3 N1 M0
IV T1-3 N2 M0
Any T, N3, M0
T4, any N, M0
Any T, any N, M1
a
Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (measured from the granular layer of adja-
cent normal epidermis to the base of the tumor); perineural invasion for T3 classification is defined as tumor cells within
the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with
clinical/radiographic involvement of named nerves without skull base invasion or transgression
266 N. P. Joshi and M. C. Tom

Table 42.2 Brigham and Women’s Hospital (BWH) 42.8 Radiotherapy

staging system for cutaneous squamous cell carcinoma [4]
High-risk factors T stage • Early skin cancers may be treated with defin-
Tumor diameter ≥2 cm T1 0 High-risk itive radiation. This can be accomplished by
factors
a variety of techniques including superficial/
Poorly differentiated T2a 1 High-risk
factor orthovoltage radiation, electron therapy,
Perineural invasion T2b 2–3 High-risk brachytherapy (mold brachytherapy or inter-
≥0.1 mm factors stitial brachytherapy), or photon therapy
Tumor invasion beyond fat T3 ≥4 High-risk • More advanced cases are treated with surgery
(bone invasion is factors or bone followed by adjuvant radiation [6] (with or
automatically T3) invasion
without chemotherapy or cetuximab)
• Definitive radiation doses and volumes differ
42.7 Surgery by the size, location and vascularity of the tis-
sue surrounding the cancer (see table below)
• Early stage cancers are usually treated with • Adjuvant radiation doses and volumes are
Mohs micrographic surgery. This is indicated extrapolated from mucosal head and neck can-
for small, well-defined primary skin cancers cers (60–66 Gy in 30–33 fractions). Similar
in areas of cosmetic importance where a neg- doses are utilized for sites outside of the head
ative complete circumferential and deep mar- and neck region, while considering adjacent
gin is desired with maximal preservation of organ at risk constraints and expected morbid-
normal tissue. This is usually followed by pri- ity. Doses and volumes for these sites usually
mary closure or local tissue rearrangement follow generally accepted guidelines for each
for closure. subsite. ACR appropriateness criteria exam-
• Larger primaries in areas where cosmesis is ples of curative radiotherapy regimens are
less important are treated with wide local summarized in Table 42.3.
excision. These primaries may be subjected
to slow Mohs margin assessment to ensure a
negative margin. This is usually followed by 42.8.1 EBRT Planning
skin grafting or free tissue transfer, espe-
cially if adjuvant radiation is indicated. • IMRT is strongly recommended for all head
• Neck dissection is usually reserved for clini- and neck cases in the adjuvant setting
cally node positive cases; select cases may • In general, pre-operative GTV = all disease
undergo an elective neck dissection. noted on exam and radiology (image fusion with
• Sentinel lymph node biopsy (SLNB) is available imaging is highly recommended)
being explored where the risk of lymph
node spread reaches or exceeds 15–20%. Table 42.3 ACR appropriateness criteria examples of
curative radiotherapy regimens [7]
This is especially useful for cases where the
a
60–70 Gy in 30–35 fractions
draining lymph node bed is less obvious and
50–55 Gy in 17–20 fractions
risk of nodal spread is higher. Caution must
40–44 Gy in 10 fractions
be exercised in sites like the head and neck 40 Gy in 5 fractions (twice weekly)
where false negative rates for SLNB may be 30 Gy in 3 fractions (once weekly)
higher. 20–25 Gy in 1 fraction
• A positive SLNB is usually followed a thera- a
Longer fractionation schedules are preferred when target
peutic lymph node dissection. volumes are in proximity to radiosensitive organs at risk
42 Skin Cancer 267

• CTV high dose = post-operative tumor bed • Additional structures like eyes, lens, optic
including the primary and positive nodes nerves, chiasm, and temporal lobes may be
(shaved off air, bone and other uninvolved added for individual cases
structures); this will include at least ipsilateral • It is recommended that doses to each of the
neck nodal levels II through IV. Levels IB, OARs be reduced as much as possible without
parotid nodes and level V are also considered at compromising PTV coverage—guidance for
risk for skin cancers. For example, levels IB dose constraints may be found in current
and parotid nodes are included for pre-­auricular/ RTOG protocols (e.g., RTOG 1016)
face and lateralized anterior scalp cancers; sub- • Relevant OARs should be delineated for non-­
occipital nodes, level V nodes are included for head and neck cases. Guidance for dose con-
post auricular and lateralized posterior scalp straints is extrapolated from protocols used for
cancers, in addition to levels II through IV. these sites.
• CTV low dose (optional) = at risk areas other
than the CTV high dose (shaved off air, bone
and uninvolved structures) 42.9 Palliative RT
• Particular attention is directed towards cover-
age of the cranial nerves at the skull base for • Standard palliative fractionation schemes
neurotropic skin cancers [8] (especially cra- include 8 Gy in 1 fraction, 20 Gy in 5 frac-
nial nerves V, VII) tions, 30 Gy in 10 fractions or Quad Shot
• The use of wires, bolus, and setup/pre-­ approach (14 Gy in 4 fractions; 2 fractions a
operative photographs is highly encouraged at day 6 h apart over 2 days repeated q 4 weeks
the time of simulation and planning to aid in up to 3 times).
designing the treatment
• PTVs (head and neck skin can-
cer) = CTV + 3 mm margin when using daily
image guidance with cone beam CT
42.10 Follow-Up
• Sites other than the head and neck are simu-
• Early skin cancers are followed clinically after
lated and treated as above. Particular attention
surgery or definitive radiation
must be paid to set up at simulation.
• Locally advanced head and neck skin can-
Customized immobilization is recommended
cers—first follow-up: CT neck and chest
when possible. Relevant nodal basin contour-
with contrast are recommended at 3 months
ing guidelines maybe referenced [9].
after adjuvant radiation/adjuvant chemora-
–– PTVs (non-head and neck sites) =
diation along with a detailed history and
CTV + 5–7 mm depending upon the site
physical exam
treated. Daily image guidance with cone
• Locally advanced non-head and neck skin
beam CT is highly recommended.
cancers—first follow-up: CT with contrast
(site based; chest is usually included)
42.8.2 OAR • Further follow-up is scheduled every 3 months
for the first 2 years, every 6 months for the
• It is highly recommended that the following next 3 years and annually thereafter
set of OARs is delineated for each head and • Further imaging is directed by symptoms or
neck case (brainstem, brainstem PRV3mm, post-treatment imaging; low dose CT chest is
cochlea, spinal cord, spinal cord PRV 5 mm, recommended for former/current smokers [10]
parotids, submandibular glands, lips, oral • Regular dental follow-up, speech and swal-
cavity, mandible, OAR pharynx, supraglottis, lowing physiotherapy, and enrolment into a
larynx or glottic–supraglottis, esophagus, tra- survivorship clinic are recommended for head
chea, and brachial plexus) and neck skin cancers
268 N. P. Joshi and M. C. Tom

• Thyroid stimulating hormone every mous cell carcinoma of the head and neck. Cancer.
6–12 months if the neck is irradiated 2017;123(11):2054–60.
2. Manyam BV, Gastman B, Zhang AY, et al. Inferior
• Sun protection and whole body skin checks outcomes in immunosuppressed patients with high-­
are recommended every 6–12 months based risk cutaneous squamous cell carcinoma of the head
on the risk of skin cancer. and neck treated with surgery and radiation therapy. J
Am Acad Dermatol. 2015;73(2):221–7.
3. Edge SB, American Joint Committee on Cancer.
AJCC cancer staging manual. 8th ed. New York:
42.11 Oncologic Outcomes [4] Springer; 2017.
4. Karia PS, Jambusaria-Pahlajani A, Harrington DP,
• 10 year cumulative incidence for local recur- Murphy GF, Qureshi AA, Schmults CD. Evaluation of
American Joint Committee on Cancer, International
rence per BWH staging Union Against Cancer, and Brigham and Women’s
–– T1 0.6% Hospital tumor staging for cutaneous squamous cell
–– T2a 5% carcinoma. J Clin Oncol. 2014;32(4):327–34.
–– T2b 21% 5. Migden MR, Rischin D, Schmults CD, et al. PD-1
blockade with cemiplimab in advanced cutane-
–– T3 67% ous squamous-cell carcinoma. N Engl J Med.
• 10 year cumulative incidence for nodal metas- 2018;379(4):341–51.
tasis per BWH staging 6. Harris BN, Pipkorn P, Nguyen KNB, et al. Association
–– T1 0.1% of adjuvant radiation therapy with survival in patients
with advanced cutaneous squamous cell carcinoma
–– T2a 3% of the head and neck. JAMA Otolaryngol Head Neck
–– T2b 21% Surg. 2019;145:153.
–– T3 67% 7. Koyfman SA, Cooper JS, Beitler JJ, et al. ACR appro-
• 10 year cumulative incidence for disease spe- priateness criteria((R)) aggressive nonmelanoma-
tous skin cancer of the head and neck. Head Neck.
cific death per BWH staging 2016;38(2):175–82.
–– T1 0% 8. Gluck I, Ibrahim M, Popovtzer A, et al. Skin cancer of
–– T2a 1% the head and neck with perineural invasion: defining
–– T2b 10% the clinical target volumes based on the pattern of fail-
ure. Int J Radiat Oncol Biol Phys. 2009;74(1):38–46.
–– T3 100% 9. Burmeister BH, Mark Smithers B, Burmeister E,
et al. A prospective phase II study of adjuvant post-
operative radiation therapy following nodal surgery
in malignant melanoma-Trans Tasman Radiation
References Oncology Group (TROG) Study 96.06. Radiother
Oncol. 2006;81(2):136–42.
1. Manyam BV, Garsa AA, Chin RI, et al. A multi-­ 10. Aberle DR, Adams AM, Berg CD, et al. Reduced
institutional comparison of outcomes of immunosup- lung-­cancer mortality with low-dose com-
pressed and immunocompetent patients treated with puted tomographic screening. N Engl J Med.
surgery and radiation therapy for cutaneous squa- 2011;365(5):395–409.
 Lymphoma
43
Rony Benson, Supriya Mallick, and Goura K. Rath

43.1 History Taking • Dyspnoea, cough, features of shortness of

breath may be seen in patients with large
Patients of lymphoma may present with one or mediastinal mass—seen in Hodgkin’s disease,
more of the following symptoms: lymphoblastic lymphoma (more with T cell)
and primary mediastinal B cell lymphoma
• Swelling in the neck, axilla or inguinal region. • Advanced high-grade lymphoma may present
• Note: Asymptomatic lymph node enlargement with high fever, tachycardia, sepsis
is the most common symptom in patients with • Fatigue and weakness generally indicate
lymphoma. Spontaneous regression of advanced stage disease
enlarged lymph nodes may be seen in some • Symptoms of extra nodal involvement (testic-
patients with low grade lymphoma ular swelling, CNS symptoms, etc.) especially
• B symptoms—Unexplained weight loss in NHL.
(>10% of total body weight) in past 6 months,
unexplained fever >38 °C or drenching night
sweats 43.2 Other Relevant History
• Fever (Classic Pel Ebstein)—High fever for
1–2 weeks, followed by an afebrile period of • Family history—Nodular sclerosis Hodgkin’s
1–2 weeks, is classically seen in Hodgkin’s lymphoma may have a genetic association.
disease
• Pruritus or pain at sites of nodal disease pre-
cipitated by drinking alcohol is also seen in 43.3 Examination
Hodgkin’s disease
Examine all lymph node areas systematically as
follows:
R. Benson (*)
Department of Medical Oncology, RCC, • Preauricular, postauricular, occipital, parotid,
Thiruvananthapuram, India neck, axilla, epitrochlear, inguinal and popli-
S. Mallick teal regions separately on both sides.
Department of Radiation Oncology, National Cancer • Examine for mass in tonsils, base of tongue or
Institute-India (NCI-India), Jhajjar, Haryana, India
adenoids
G. K. Rath • Look for associated hepatosplenomegaly
Dr. B. R. Ambedkar Institute-Rotary Cancer Hospital,
All India Institute of Medical Sciences, • Examine for features of superior vena cava
New Delhi, India obstruction.

© Springer Nature Singapore Pte Ltd. 2020 269

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_43
270 R. Benson et al.

43.4 Differential Diagnosis Stage II indicates that the disease is located in

two lymph node separate regions, confined to one
• Non-Hodgkin’s lymphoma—Non-contiguous side of the diaphragm
lymph nodes in older patients Stage III indicates that the disease has spread
• Hodgkin’s lymphoma—Contiguous lymph to both sides of the diaphragm
nodes of neck and mediastinum with rubbery Stage IV indicates diffuse or disseminated
consistency and possibly Pel Ebstein fever involvement of one or more extra lymphatic
• Metastatic lymph nodes—Hard lymph nodes organs, (liver, bone marrow, or nodular involve-
which are often matted ment of the lungs)
• Benign reactive lymph nodes—Especially
limited to inguinal or submandibular area • B: presence of B symptoms (fever (tempera-
(generally <2 cm, soft, mobile non-matted) ture >38 °C), drenching night sweats,
• Infections unexplained loss of >10% of body weight
­
1. CMV—Infectious mononucleosis—Tender within the preceding 6 months) if not A
lymph node, pharyngitis, Heterophile Test+ • S: spread to the spleen
2. TB—Non-tender lymph node with fever • E: spread to extranodal organ
3. HIV—Rash, fever, diarrhoea and loss of • X: is used to indicate bulky disease (>10 cm
weight large/ bulky mediastinal disease)
4. Leprosy—Lymph node with nerve • Note: The lymphatic system includes lymph
enlargement nodes, spleen, thymus, Waldeyer ring, appen-
• Sarcoidosis—Predominantly mediastinal lymph dix, and Peyer’s patches.
nodes with wheeze and skin involvement.

43.7 Prognostic Indices

43.5 Work-Up
Various prognostic indices useful in lymphoma
• CBC/LFT/KFT/ ESR/LDH are summarised in Table 43.1.
• CECT neck, chest, abdomen and pelvis (OR)
PET scan (in HL and high-grade NHL)
• Bone marrow study—can be avoided in 43.8  reatment Outline Hodgkin’s
T
selected patients with PET negativity and Lymphoma
absence of B symptoms
• Cardiology (Echocardiography—if planned Treatment outline in Hodgkin’s lymphoma is
for adriamycin), pulmonary function test (if summarised in Table 43.2.
planned for bleomycin)
• Excision biopsy of the lymph node
• Reproductive counselling (younger patients) 43.9  reatment Outline Non-­
T
and urine pregnancy test (younger female Hodgkin’s Lymphoma
patients).
Treatment outline in non-Hodgkin’s lymphoma
is summarised in Table 43.3.
43.6  taging: Modified Ann
S
Arbour Staging
43.10 Radiotherapy
Stage I indicates that the disease is located in a
single lymph node region Involved field radiotherapy (IFRT) [1]
43 Lymphoma 271

Table 43.1 Prognostic indices in lymphoma

The GHSG unfavourable risk 1. Presence of a large mediastinal mass, Presence of one or more factors makes it
factors (stage I and II measured by means of a chest X-ray; unfavourable and treatment plan gets
Hodgkin’s lymphoma) one third of the transverse diameter of modified as mentioned below
the thorax
2. Extra-nodal disease
3. High erythrocyte sedimentation rate
(ESR) of 50 mm/h if B-symptoms are
absent and 30 mm/h if B-symptoms are
present
4. Involvement of three or more lymph
node areas
International prognostic index • Age >60 year Estimated 5 year survival
for NHL • PS 2–4 • Low (score 0/1) 73%
• Stage 3 or 4 • Low intermediate (score 2) 51%
• Elevated LDH • High intermediate (score 3) 43%
• >1 extra nodal site • High (score 4 or 5) 26%
FLIPI scoring for • >4 involved nodal sites Score 5 year OS 10 year OS
follicular lymphoma • Elevated LDH
0-1 91 71
• Age ≥60 years
• Advanced stage III/IV disease 2 78 51
• Haemoglobin <12 g/dL ≥3 53 36

Table 43.2 Treatment outline in Hodgkin’s lymphoma

NLPHL I/IIA—IFRT alone 30–36 Gy (IFRT 30 Gy F/B Boost of 6 Gy)
If less than CR → chemo (ABVD/CHOP)
ADVANCED STAGE—Chemo ABVD/ CHOP
Rituximab may be added
EARLY FAVOURABLE DISEASE 2 ABVD F/B IFRT (20 Gy/10#/2 weeks)
CHL
EARLY UNFAVOURABLE DISEASE 2 ABVD + 2 escalated BEACOPP F/B IFRT (30 Gy/15#/3 weeks)
CHL
LATE DISEASE CHL 6 cycles of ABVD
IFRT if indicated—residual/ bulky disease

Table 43.3 Treatment outline in Hodgkin’s lymphoma

Stage Treatment
Indolent lymphoma Stage I-II-contiguous IFRT
(follicular lymphoma—grade 1/2 non-bulky (<7.5 cm)
SLL, marginal zone lymphoma) Advanced stage Chemoimmunotherapy—If indication for
treatment
Palliation-RT
Aggressive Stage I-II non-bulky • Combined modality therapy with abbreviated
DLBCL (<7.5 cm) and no chemotherapy (4 × CHOP ± R[if CD20+]
FL-grade III extra-nodal disease followed by IFRT)
OR
• Full chemotherapy alone (6 × CHOP ± R[if
CD20+])
Stage I-II bulky/stage III/ • 6–8 × CHOP ± R[if CD20+]
IV • RT bulky or residual
Very aggressive Lymphoblastic lymphoma ALL like protocol, consolidation RT given
residual disease/extra nodal sites
PCI is given
Burkitt ALL like protocol
No PCI
272 R. Benson et al.

Table 43.4 Treatment borders of IFRT

Upper border Lower border Medial border Lower border
Neck[I/L] 1–2 cm above 2 cm below clavicle Ipsilateral transverse Include medial
mastoid tip processofvertebraifSCF− two-third of clavicle
Contralateral
transverse process of
vertebra if SCF+
Mediastinum C5/6 5 cm below carina/2 cm NA Hilar area +1/1.5 cm
below pre-chemo disease OR
Post-chemo
disease+1/1.5 cm
Axilla C5/6 Tip of scapula/2 cm below Ipsilateral cervical Flash in sin
pre-chemo disease transverse process
Para-aortic T11 upper L4 lower border NA Edge of transverse
border process of vertebra
Inguinal Mid sacroiliac 5 cm below lesser Medial obturator 2 cm lateral to greater
joint trochanter foramen/2 cm medial trochanter
to midline

• Encompasses the nodal region and not the Table 43.5 Comparison of INRT vs ISRT
individual nodes INRT ISRT
• Major involved-field regions CTV = pre CTV = pre-chemotherapy
1. Neck (unilateral) chemotherapy extent of extent of involved lymph
involved lymph nodes nodes with an expansion of
2. Mediastinum (including bilateral hilum)
modified within 1.5 cm in the craniocaudal
3. Axilla (including supraclavicular and post-chemotherapy direction of lymphatic
infraclavicular) anatomical changes spread
4. Spleen PTV was created by PTV was created by
5. Paraaortic adding an isotropic adding an isotropic margin
margin of 1 cm of 1 cm
6. Inguinal (femoral and iliac nodes).
Smaller volumes Higher volumes in
• Initially involved prechemo sites and volume supero-inferior direction
are treated, except for the transverse diameter Very difficult to More easy to implement
of mediastinal and PA LN for which the implement
reduced post-chemotherapy volume is treated
• Treatment borders of IFRT are summarised in • In most centres, pre-chemotherapy PETCT
Table 43.4. scans are not carried out in the radiotherapy
treatment position with immobilisation
Involved-nodal radiotherapy (INRT) [2, 3] devices as required for INRT
• Logic for INRT—pattern of relapse in patients • Hence ISRT—A more practical approach
treated with chemotherapy alone showed that • Pre-chemotherapy extent of disease is
most recurrences occurred in the initially expanded cranio-caudally by 1.5 cm in the
involved lymph nodal area. Smaller radiation direction of lymphatic spread to form IS-CTV
fields should also lead to a decrease in late • Comparison of INRT vs ISRT is summarised
complications as the amount of irradiated nor- in Table 43.5.
mal tissue is reduced
• INRT design requires accurate pre-chemo or pre-
biopsy information PET in the treatment position 43.11 EBRT Planning
• Pre-chemotherapy extent of involved lymph
nodes modified within post-chemotherapy Treatment Position
anatomical boundaries to form IN-CTV. • Hyperextension for neck nodes
• Axilla-Akimbo position helps shield shoulder,
Involved Site RT (ISRT)
also minimal skin folds in axilla
43 Lymphoma 273

Arms above head—pulls axillary nodes away 43.12 Follow-Up

from chest, hence helps maximal sparing of lung
The patients may be followed up every 3 month
Radiotherapy Dose Hodgkin’s Lymphoma for 2 years and then 6 monthly till 5 years and
then annually
• Early favourable—20 Gy/10#/2 weeks Physical examination to be done in each visit
• Early unfavourable/ Investigations
advanced—30 Gy/15#/3 weeks
• Residual disease—May increase dose up to • CBC each visit
36 Gy • PET CT at three months to verify complete
• NLPHD-Stage I/IIA—IFRT alone 30–36 Gy. metabolic response. No routine imaging
needed after that
Radiotherapy Dose Non-Hodgkin’s Lymphoma • 2 D Echo after 10 years
• Breast evaluation by breast MRI after 8 years
• Indolent lymphoma—24 Gy/12#/2.5 weeks in females if RT to mediastinum
• Aggressive lymphoma—30 Gy/15#/3 weeks • TSH—annually if RT to neck
• Residual disease 36–40 Gy
• Palliative RT
• Indolent—24 Gy/12# or 4 Gy/2# (90%
References
response—explained by the predominant
mode of tumour cell death largely mediated 1. Yahalom J, Mauch P. The involved field is back:
by apoptosis) issues in delineating the radiation field in Hodgkin’s
• Aggressive 30 Gy/10. disease. Ann Oncol. 2002;13(Suppl 1):79–83.
2. Girinsky T, van der Maazen R, Specht L, Aleman B,
Poortmans P, Lievens Y, et al. Involved-node radio-
Radiotherapy Dose Extra nodal Non-­ therapy (INRT) in patients with early Hodgkin lym-
Hodgkin’s Lymphoma [4] phoma: concepts and guidelines. Radiother Oncol.
2006;79(3):270–7.
• Generally 30 Gy/15# as ISRT, treat the 3. Girinsky T, Specht L, Ghalibafian M, Edeline V,
Bonniaud G, Van Der Maazen R, et al. The conun-
involved site with margins of 2 cm drum of Hodgkin lymphoma nodes: to be or not to
• Primary CNS lymphoma—WBRT 45 be included in the involved node radiation fields.
Gy/25#/5 weeks may be reduced to 30–36 Gy The EORTC-GELA lymphoma group guidelines.
if CR in chemotherapy (chemotherapy follows Radiother Oncol. 2008;88(2):202–10.
4. Yahalom J, Illidge T, Specht L, Hoppe RT, Li YX,
the De Angelis protocol) Tsang R, et al. Modern radiation therapy for extra-
• Sino-Nasal NK cell lymphoma—RT higher nodal lymphomas: field and dose guidelines from the
dose 45–50 Gy (chemotherapy includes International Lymphoma Radiation Oncology Group.
SMILE regimen) Int J Radiat Oncol Biol Phys. 2015;92(1):11–31.
 Carcinoma Lung
44
Sandeep Muzumder and M. G. John Sebastian

44.1 History Taking [1, 2] 44.1.3 Pancoast Syndrome

• Cough • Shoulder pain

• Dyspnoea • Horner’s syndrome
• Wheeze • Brachial plexopathy.
• Haemoptysis
• Chest pain
• Recurrent laryngeal nerve involvement: 44.1.4 Paraneoplastic Syndrome
Hoarseness of voice
• Phrenic nerve involvement: hiccups, shortness • Cushing syndrome
of breath due to unilateral paralysis of • Syndrome of inappropriate antidiuretic hor-
diaphragm mone secretion
• Weight loss. • Hypercalcemia
• Lambert-Eaton myasthenic syndrome
• Hypertrophic osteoarthropathy.
44.1.1 Other Relevant History

• Smoking 44.2 Examination

• Family history of lung cancer
• Exposure to asbestos/radon • Performance status (ECOG/KPS)
• Passive smoking. • Build and nourishment
• Pallor, icterus, clubbing, cyanosis, lymphade-
nopathy, oedema
44.1.2 Superior Vena-Cava • PR/BP/RR/temperature
Syndrome • Respiratory system examination
• Inspection: Upper respiratory tract including
• Sensation of fullness in the head and dyspnoea nose and oral cavity, shape of the chest, sym-
• Swelling of the face and arms. metry, position of trachea, apex beat, respira-
tory movements, respiratory rate, rhythm and
type, scars, sinuses, visible pulsations, dilated
S. Muzumder (*) · M. G. John Sebastian veins, oedema
Radiation Oncology, St. John’s Medical College and
Hospital, Bengaluru, India

© Springer Nature Singapore Pte Ltd. 2020 275

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_44
276 S. Muzumder and M. G. John Sebastian

• Palpation: Position of trachea, respiratory 44.5 Staging

movements, vocal fremitus, tenderness of
chest wall T1. Tumour ≤3 cm surrounded by lung or vis-
• Percussion: Pleural effusion ceral pleura without bronchoscopic evidence of
• Auscultation: Intensity and type of breath invasion more proximal than the lobar bronchus
sounds, any adventitious sounds, vocal reso-
nance, any miscellaneous sounds • T1a Tumour ≤1 cm
• Cardiovascular system • T1b Tumour >1 cm but ≤2 cm
• Central nervous system: Higher mental • T1c Tumour >2 cm but ≤3 cm.
functions/cranial nerve examination/sen-
sory ­system/motor system/any signs of T2. Tumour >3 cm and ≤ 5 cm or tumour and
meningeal irritation/skull and spine involves main bronchus or visceral pleura or atel-
examination ectasis or obstructive pneumonitis
• Gastrointestinal system: Hepatomegaly/other
palpable mass/ascites. • T2a Tumour >3 cm but ≤4 cm
• T2b Tumour >4 cm but ≤5 cm.

44.3 Differential Diagnosis T3.

• Carcinoma lung • Tumour >5 cm and ≤ 7 cm

• Tuberculosis • Separate tumour nodule(s) in the same lobe of
• Bronchopneumonia lung
• Mediastinal mass: Lymphoma/thymoma/ • Tumour that invades: chest wall, phrenic
GCT/neurogenic mass nerve, or parietal pericardium.
• Sarcoidosis.
T4.

44.4 Work-Up • Tumour >7 cm

• Separate tumour nodule(s) in a different ipsi-
• Blood work-up: CBC, LFT, RFT, Serum lateral lobe
sodium, potassium, calcium, magnesium • Invades: diaphragm, mediastinum, heart, great
• Radiological investigations: vessels, trachea, recurrent laryngeal nerve,
• Chest X-ray AP/lateral esophagus, vertebral body and carina.
• Contrast enhanced CT scan of thorax and
abdomen Nodal
• PETCT scan
• Tissue diagnosis: • N1—ipsilateral peribronchial or hilar lymph
–– Sputum cytology nodes
–– CT guided FNAC/biopsy • N2—ipsilateral mediastinal nodes
–– Bronchoscopy: Cytologic brushings, • N3—contralateral mediastinal, or supracla-
biopsy vicular lymph node.
–– Endoscopic ultrasound-guided trans-­
bronchial fine needle aspiration (EBUS- Metastasis:
TBNA)
–– Thoracentesis • M1a—Separate tumour nodule(s) in a contra-
–– M e d i a s t i n o s c o p y / m e d i a s t i n o t o m y / lateral lobe; pleural or pericardial nodules or
thoracotomy. malignant pleural or pericardial effusion
44 Carcinoma Lung 277

• M1b—Single extra thoracic mets 44.7 Treatment Outline

• M1c—Multiple extra thoracic mets.
Treatment outline in non-small cell lung cancer
The AJCC eighth edition 2017 stage grouping and small cell lung cancer is summarised in
and stage specific survival is summarised in Tables 44.2 and 44.3.
Table 44.1 [3].

44.8 Radiotherapy Dose

44.6 Screening
• NSCLC: 66 Gy in 33 daily fractions of 2 Gy in
Low dose CT advised in the following setting, 6.5 weeks with concurrent chemotherapy.
after a discussion of risks and benefits between • SCLC: 45Gy in 30 twice daily fractions along
physician and patient. with 4–6 cycles of cisplatin and etoposide 3
weekly. The first cycle of chemotherapy was
• Age 55–74 years given before radiotherapy and the second was
• A history of smoking at least 30 pack years given concurrently with radiotherapy (etopo-
• Current smoker or has quit smoking foe less side 100 mg/m2 iv on D 1–3 and cisplatin
than 15 years. 25 mg/m2 iv on D 1–3).

Table 44.1 The AJCC 2017 staging with stage specific survival of lung cancer
Lung cancer staging c 2 years OS c 5 years OS p 2 years OS p 5 years OS
Occult carcinoma TxN0M0
Stage 0 TisN0M0
Stage 1 IA 1A1 T1mi-1aN0M0 97 92 97 90
1A2 T1bN0M0 94 83 94 85
1A3 T1cN0M0 90 77 92 80
IB T2aN0M0 87 68
Stage 2 IIA T2bN0M0 79 60 82 65
IIB T1a-3N1M0, T3N0M0 72 53 76 56
Stage 3 IIIA T1a-2bN2M0, T4 N0–1 M0 55 36 65 41
IIIB T1a-2bN3M0, T3-4N2M0 44 26 47 24
IIIC T3-4N3M0 24 13 38 12
Stage 4 IVA Any T, any N, M1a-M1b 23 10
IVB Any T, any N, M1c 10 0

Table 44.2 treatment outline in non-small cell lung cancer

Non-Small Cell Lung Cancer [4–7]
Stage I, II Surgical exploration with I: Adjuvant RT for positive marginsa
resection and mediastinal IIA and above: Adjuvant RTCT for positive
lymph node dissection/ marginsa
sampling Adjuvant chemotherapy for all N1
Adjuvant CTRT for all N2
Clinically N2-3M0 disease Definitive CTRT
Stage IIIA(T4 N0–1) Resectable: surgery
Non resectable: definitive CTRT
Superior sulcus tumour: possibly NACTRT f/b evaluation Resectable: surgery
resectable Non resectable: continue CTRT
Unresectable disease i/v/o of local extensions can be considered for definitive CTRT if amenable
Medically inoperable cases can be considered for Definitive RT/RTCT
a
Only if reresection not planned
278 S. Muzumder and M. G. John Sebastian

Table 44.3 treatment outline in small cell lung cancer

Small Cell Lung Cancer [8–12]
Stage I Lobectomy + Mediastinal lymph node N0-N1: Adjuvant CT
dissection N2: Adjuvant CTRT
Limited stage Definitive CTRT
Extensive stage Patient tailored treatment
• Limited stage: Confined to ipsilateral hemithorax which can be safely encompassed within a radiation field
(included I/L and C/L mediastinal and I/L hilar and supra-clavicular)
• Extensive stage: Disease beyond the ipsilateral hemithorax including malignant pleural or pericardial effusion
or hematogenous metastasis
(Veterans Association Lung Study group-1950)
• Limited stage: Stage I to III (any T, any N, M0) that can be safely treated with definitive radiotherapy
• Extensive stage: Stage IV (any T, any N, M1a/b) or T3 or T4 with multiple lung lesions that are too extensive to
be encompassed in a tolerable radiation plan
(Based on 2010 TNM; IASLC Review)

44.9 Radiotherapy Planning contrast is performed in treatment position.

Volumes Patient should be breathing normally. 2.5 mm
slice images are taken from zygoma to lower
44.9.1 2D-EBRT Planning border of liver. Fuse the PET CT scan images.
Whenever possible a 4DCT scan should be
44.9.1.1 Upper Lobe Tumours done to identify complete tumour movement
• Bilateral supraclavicular field during respiration.
• Upper mediastinum • Contouring: Gross tumour volume (primary
• Subcarinal field (two vertebra below carina) or nodal) is contoured based on PET
or (five to six centimetres below carina) images.
• Primary tumour +2 cm. • A CTV margin of 6 mm for squamous histol-
ogy and 8 mm for other histology is to be
44.9.1.2 Hilar Tumours given. PTV margins are being given based on
• Superior: thoracic inlet department protocol (Fig. 44.1).
• Inferior: 8–9 cm below carina
• Includes mediastinum
• Primary tumour +2 cm 44.10.1 Stereotactic Radiotherapy
44.9.1.3 Lower Lobe Tumours In medically inoperable patients with T1, T2 N0
• Superior: thoracic inlet. diseases.
• Inferior: up to the diaphragm.
• Includes mediastinum.
• Primary tumour +2 cm.
44.11 Post-Operative
Radiotherapy in Carcinoma
44.10 Conformal Radiotherapy Lung [13]

• Treatment position: Supine, with arms above 44.11.1 Indications

head. Immobilisation using chest board and
fixed arm position. The patient should be 1. R0 resection with N2 disease.
breathing normally. 2. R1 (extracapsular extension in node) and R2
• Simulation: Patient is asked to be nil per oral resections when reresection not possible (any
for 4 h. A planning CT scan with intravenous stage).
44 Carcinoma Lung 279

Fig. 44.1 Contouring, beam arrangement, and planning in patient with non-small cell lung cancer

44.11.2 Sequencing
with Chemotherapy 44.14 Follow-Up

1. In N2 disease radiotherapy should be given Repeat CT scan/PET CT scan after 2–3 months
sequentially after chemotherapy. of treatment completion for response evaluation.
2. In R1 and R2 resections radiotherapy can be Follow-up every 3–6 months for 2 years, then
given either sequentially after chemotherapy annually.
or concurrent with chemotherapy.

44.15 Recurrence
44.11.3 Dose
Loco-regional: Salvage surgery or chemoradia-
1. R0 resection 50–54 Gy in 1.8–2.0 Gy\ tion; palliative radiation therapy or chemotherapy.
fraction. Distal metastasis: Palliative chemotherapy or
2. R1 resection 54–60 Gy in 1.8–2.0 Gy\fraction. radiation therapy.
3. R2 resection 60 Gy in 1.8–2.0 Gy\fraction.

44.16 Case Report 1: NSCLC

44.12 Palliative Radiotherapy
A 58-year-old male presented to the out-patient
Dose: 30Gy in 10 fractions in Department of Pulmonary Medicine with history
of fever and dry cough for 3 months duration. He
• Symptomatic advanced disease/poor perfor- gives history of smoking around 10 cigarettes per
mance status day for past 25 years and consuming alcohol of
• Symptomatic metastatic sites: bone/brain/ around 90 ml per day for past 30 years.
node. He was evaluated with a chest X-ray which
showed patchy opacity in left upper lobe. A CECT
thorax revealed a 2.3 × 2 cm mass in left upper lobe
44.13 Prophylactic Cranial with centrilobular emphysema in both lungs. A
Irradiation [14–16] PETCT showed a 2 × 1.9 × 1.9 cm metabolically
active soft tissue density nodule with speculated
• Limited stage SCLC who had a partial/com- margins in the apico-posterior segment of left upper
plete response after definitive treatment. lobe of maximum SUV 11.4 and multiple metaboli-
• Extensive stage disease showing good cally active lymph nodes in aortopulmonary window
response to chemotherapy. and subcarinal region with maximum SUV: 2.9.
• Recommended dose is 2500 cGy in 10 A CT guided biopsy of the lung nodule was
fractions. done. Histopathological examination was sug-
280 S. Muzumder and M. G. John Sebastian

gestive of infiltrative neoplasm. The neoplastic complaints of loss of weight and loss of appetite
cells were positive for CK7 and TTF1 and neg- over 2 months. He gives history of smoking
ative for P63 and CK20. Histomorphology and around 25 beedis per day for past 40 years.
immuno-profile were consistent with a primary A contrast enhanced CT scan showed an ill-­
pulmonary adenocarcinoma. defined right hilar lesion compressing the supe-
A diagnosis of carcinoma left lung cT1N2M0; rior vena cava, right pulmonary artery, right main
Stage IIIB was made according to AJCC seventh bronchus and its branches. Another 16 × 11 mm
edition. speculated lesion was seen in posterior segment
Patient was planned for definitive chemoradia- of right upper lobe with no enlarged mediastinal
tion to a dose of 6000 cGy in 30 fractions along nodes. A video-bronchoscopy showed a growth
with 2 cycles of concurrent 3 weekly pemetrexed completely obstructing the bronchi supplying the
and carboplatin (C1—5 days before RT, C2—on upper lobe. The endobronchial biopsy of the
14th day of RT, C3—10 days after completing RT). lesion was suggestive of a small cell lung
Radiotherapy planning was done on GE carcinoma.
Lightspeed 4 Slice CT machine and 2.5 mm Patient was diagnosed as small cell lung carci-
images were accrued and was transported to noma cT3N0M0 (Stage IIB), limited stage.
MONACO version 5.10.04 contouring station. Patient was planned for definitive chemo
Organs at risk in the field of irradiation including radiation to a dose of 4500 cGy in 30 fractions
bilateral lungs, heart, spinal cord and oesophagus along with 2 cycles of concurrent 3 weekly cis-
were contoured. The planning CT scan images platin and etoposide (C1—7 days before RT,
were fused with PET-CT and gross tumour vol- C2—on 13th day of RT). He received 2 more
umes (GTV) were marked. An 8 mm symmetri- cycles of adjuvant chemotherapy with cisplatin
cal margin was given to GTV primary and 5 mm and etoposide. He received prophylactic cranial
symmetrical margin to GTV nodes. PTV margins irradiation to a dose of 2400 cGy in 8 fractions
were 1 cm cranio-caudal and 7 mm axial. A after completing adjuvant chemotherapy
3-dimensional conformal radiotherapy plan was (Fig. 44.2).
generated using XIO treatment planning system. Radiotherapy planning was done on GE
During treatment he developed Grade 3 Lightspeed 4 Slice CT machine. Images were
esophagitis, Grade 1 skin reaction and Grade 2 accrued at 2.5 mm thickness and were trans-
pain which were managed conservatively. ported to MONACO contouring station. Organs
A PETCT scan done 1 month after completion at risk in the field of irradiation including bilat-
of radiotherapy showed a decrease in size of the left eral lungs, heart, spinal cord and oesophagus
upper lobe mass measuring 18 × 13 × 7 mm with were contoured. Gross tumour was marked as per
max SUV 1.8 and complete metabolic response of
the lymph nodes. Patient received two more cycles
of adjuvant chemotherapy with pemetrexed and
carboplatin. A CECT scan done after treatment
showed no mass lesions in bilateral lungs and
mediastinum indicating no evidence of disease.
Patient is on regular follow-up. The patient
has a disease-free survival of 2 years and
10 months till date.

44.17 Case Report 2: SCLC

A 60-year-old male presented to the out-patient

Department of Pulmonary Medicine with history
of fever and cough for months duration. He also Fig. 44.2 Prophylactic cranial irradiation planning
44 Carcinoma Lung 281

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radiation therapy in locally advanced non-small cell
given to GTV primary. PTV margins were 1 cm lung cancer: executive summary of an American
cranio-caudal and 7 mm axial. A 3-dimensional Society for Radiation Oncology (ASTRO) evidence-­
conformal radiotherapy plan was generated using based clinical practice guideline. Pract Radiat
XIO treatment planning system. Oncol. 2015;5:141–8. https://doi.org/10.1016/j.
prro.2015.02.012.
Patient developed Grade 2 esophagitis, Grade 3 8. Miller AB, Fox W, Tell R. Five-year follow-up of
neutropenia which were managed conservatively. the Medical Research Council’s comparative trial of
Patient is doing well on last follow-up and has surgery and radiotherapy for the primary treatment
a disease-free survival of 4 years and 2 months. of small-celled and oat-celled carcinoma of the bron-
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9. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry
• Consent of the patient 1 and 2 has been taken MC, Souhami RL, Brodin O, Joss RA, Kies MS,
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randomised controlled trials. Cancer Treat Rev.
2007;33(5):461–73.
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Natl Cancer Inst. 2011;103:1452–60.
 Part VI
Other Relevant Topics
 Critical Appraisal of a Clinical Trial
45
Bhanu Prasad Venkatesulu

Clinical trials form the backbone of evidence-­ chemotherapy-­based studies which are inap-
based medicine. General tendency of a resident is propriate trial design.
to read the abstract of clinical trial and conclude 2. Read the protocol of the study previously pub-
if the trial is significant or not (https://hand- lished and confirm if the endpoints and trial
book-5-1.cochrane.org). We have tried to sim- design are similar [1].
plify the process on how to evaluate a trial in a 3. Sample size calculation.
clear manner 4. The trial design—Superiority trial, non-­
inferiority trial, or equivalence trial.
1. Is the research question of the clinical trial 5. Look for the following biases in the study.
appropriate? Is the population, intervention,
comparators, and the endpoints assessed are Table 45.1 lists the checklist for critical
appropriate?—There is a tendency to assess appraisal of a clinical trial.
placebo vs new intervention; especially

B. P. Venkatesulu (*)
MD Anderson Cancer Center, Houston, TX, USA

© Springer Nature Singapore Pte Ltd. 2020 285

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_45
286 B. P. Venkatesulu

Table 45.1 Checklist for critical appraisal of a clinical trial

Random sequence How was the randomization process done?
generation For example, central telephonic randomization, table of random numbers, computer random
number generator
Allocation How was the allocation of numbers concealed?
concealment For example, radiopaque envelopes, web-based allocation
Blinding/matching If the outcome is definitive endpoint like overall survival—open label study is acceptable
Quality of life studies—preferable that the physician and the patient are blinded to the
intervention and the outcomes are reported by the patient
Attrition bias If any trial has attrition rate more than 10%, then either the intervention is too detrimental or
too beneficial that the patients do not follow up
Selective The study’s prespecified outcomes are not reported in complete totality. Typically if the
reporting bias intended outcomes is contrary to expectations or makes a trial negative study, the trial authors
tend to omit the outcome
Other biases Funding source
Conflict of interest of the trial authors
Whether the trial was monitored by independent data monitoring committee
Whether the analysis was intention to treat or per protocol analysis
Whether the cost-effectiveness of the intervention is reported
The universal applicability of the trial
Route of administration of the intervention
Whether the intervention is acceptable to patient’s cultural values

1. Al-Jundi A, Sakka S. Critical appraisal of clinical

Reference research. J Clin Diagn Res. 2017;11(5):JE01–5.
 Radiation Toxicity
46
Supriya Mallick, Rony Benson, and Goura K. Rath

Common radiation side effects include: Table 46.1 Comparison of acute and late radiation
toxicity
1. Dermatitis Acute Chronic
2. Mucositis Tissue with high cell turnover Tissues with slow
rate (mucosal membrane/skin) cell turnover
3. Pneumonitis
Usually transient Persistent/
4. Cystitis progressive
5. Proctitis Dose per fraction not very Fraction size
6. Cardiac toxicity important matters
7. Hepatic toxicity

Radiation toxicity can be divided into acute Table 46.2 Summary of skin changes following
radiotherapy
and late toxicity (Table 46.1):
Dose (Gy) Onset
• Acute—during or within few weeks after RT, Early transient erythema 2 Hours
Faint erythema 6–10 7–10 days
main pathology is inflammation
Definite erythema/hyper 12–20 2–3 weeks
• Chronic—seen months to years after therapy pigmentation
(>6 months, RTOG uses 3 months), main Dry desquamation 20–25 3–4 weeks
pathology is vascular Moist desquamation 30–40 4 weeks
Ulceration >40 6 weeks

46.1 Temporal Association

Table 46.3 Temporal association of other radiation tox-
icity following head and neck radiotherapy
Skin changes: The skin changes show a peculiar
temporal association (Table 46.2) as well as other Dose (Gy) Onset
toxicity in head and neck also shows temporal Taste loss 10 Gy 1st week
Mucositis 15–20 Gy 2nd week
association (Table 46.3).
Hyposalivation 20–25 Gy 2nd week–3rd week
Radiation caries 55–60 6th week
S. Mallick (*) · R. Benson · G. K. Rath
Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India

© Springer Nature Singapore Pte Ltd. 2020 287

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_46
288 S. Mallick et al.

46.2 Management of Radiation • Smoking and tobacco increase the risk of radi-
Toxicity ation dermatitis
• There is increase in incidence of radiation skin
1. Prevention of radiation toxicity is most impor- toxicity as age increases
tant, this can be achieved by
(a) Patient selection
(b) Nutrition 46.3.2 Grading
(c) Comorbidity
(d) Syndromic association • Grade I—Presence of faint erythema/epila-
(e) Good radiation planning, IMRT tion/dry desquamation/decreased sweating
2. Treatment approach • Grade II—Presence of bright erythema/patchy
(a) Regular evaluation moist desquamation/moderate edema
(b) Interruption when required • Grade III—Presence of confluent, moist des-
(c) If >grade II introduction of management quamation at areas other than skin folds/pres-
ence of pitting edema
• Grade IV—Presence of ulcer, necrosis, or
46.3 Radiation Dermatitis hemorrhage

Radiation dermatitis was one of the common

dose limiting side effects in patients receiving 46.3.3 Prevention of Radiation
radical radiotherapy. The incidence is decreas- Dermatitis
ing with the use of more conformal and higher
energy radiation techniques. The incidence is 1. Avoid shaving and tight clothing
also decreasing with the less frequent use of 2. Avoid mechanical injuries
telecobalt and more availability of linear 3. Avoid smoking
accelerator. 4. Avoidance of hot spots in skin during radia-
The main pathophysiology includes damage tion planning
to the stem cells in the basal layer of the skin, 5. Conformal or intensity modulated radiother-
thereby preventing the process of repopulation. apy to reduce the normal tissue irradiated
6. Reduce sun exposure
7. Only gentle washing of irradiated area with
46.3.1 Risk Factors mild soaps

• Higher incidence with telecobalt than linear

accelerators 46.3.4 Treatment of Radiation
• Incidence is higher in areas with skin folds Dermatitis
like inguinal area even with same dose
• Volume of skin treated, with higher risk with • Grade I reaction—consider emollients and
more volume irradiated, due to higher damage moisturizers, consider prophylactic steroids
to stem cells • Sitz bath if irradiation of perianal or pelvic
• Radiation dose—Dry desquamation starts areas
with 20–25 Gray and moist desquamation • Diagnose and early treatment of secondary
occurring at 30–40 Gray infection
• Chemotherapy use can increase skin toxicity, • Analgesics including narcotic analgesics for
e.g., cisplatin, 5-fluorouracil pain
46 Radiation Toxicity 289

• Treatment breaks if grade III or higher skin • Grade III—Confluent fibrinous mucositis/
toxicity, and restart treatment once reaction severe pain requiring narcotic analgesic for
resolves pain control
• Reassurance and psychiatric counseling of the • Grade IV—Presence of ulceration, necrosis,
patient if anxious or hemorrhage

46.4 Radiation Mucositis 46.4.3 Prevention of Radiation

Induced Oral Mucositis
Mucositis is a treatment limiting acute side
effect of radiotherapy for head and neck cancer. 1. Pretreatment oral cavity check-up
It has significant impact on treatment and limits 2. Maintaining good oral hygiene and use a soft-­
the oral intake and causes treatment breaks in bristle toothbrush to maintain oral hygiene
patient undergoing radiotherapy for head and 3. Avoid hot and spicy food items, smoking, and
neck cancer [1] alcohol during radiotherapy
4. Better radiation planning, e.g., conformal or
• The spectrum of oral mucositis includes oral intensity modulated radiotherapy to reduce
pain, odynophagia, reduced oral intake, and the normal tissue irradiated
secondary infections 5. Benzydamine: Incidence of oral mucositis
• Rapidly dividing cells in the mucosa of the may be reduced by 2.6 times with benzyda-
oral cavity and oropharynx irradiated are par- mine mouthwash. (Chlorhexidine mouth gar-
ticularly susceptible gles is only recommended for chemotherapy
• The incidence of radiation mucositis is signifi- induced oral mucositis)
cantly increased by adding concurrent 6. Prophylactic low level laser therapy (LLLT):
chemotherapy by diode lasers including red and infrared
• The incidence of grade 3 or higher mucositis wavelengths
is higher in patients receiving altered fraction-
ation radiotherapy (56%) vs conventional
radiotherapy (34%) 46.4.4 Treatment of Radiation
Induced Oral Mucositis

46.4.1 Risk Factors 1. Benzydamine mouth gargles

2. Treatment of secondary infection in patients
1. Age > 65 years with oral mucositis
2. Baseline poor oral hygiene 3. Oral mucosa should be sent for bacterial and
3. Periodontal diseases fungal culture and sensitivity—antimicrobials
4. Reduced saliva production may be tailored accordingly
5. Poor nutritional status 4. Treatment interruption may be required in
6. Co-morbidities—Diabetes, predisposes to severe OM (Grade III or IV)
secondary infection 5. Feeding—Application of local anesthetics
before food. Liquid or semisolid food with
high calorie and protein may be very helpful
46.4.2 R
 TOG Grading of Oral and in severe mucositis. Some patients may
Mucositis also require alternate enteral feeding
6. Pain control; initial weeks may be controlled
• Grade I—Irritation/mild pain not requiring by topical analgesics including aspirin and
analgesic for pain relief lignocaine. Later morphine mouth gargles
• Grade II—Patchy mucositis with serosangui- may be required for controlling oral pain asso-
nous discharge/moderate pain requiring ciated with mucositis and may reduce the
analgesia need for systemic morphine. Doxepin oral
290 S. Mallick et al.

rinses may be also helpful in reducing pain of cies (ROS) and β-TGF production occurs by the
oral mucositis 6th week which subsequently leads to radiation
7. LLLT with low level He– Ne laser therapy induced lung fibrosis. Endothelial destruction
8. Radiation should be started early as mucositis also occurs which leads to neo-vascularization
heals as prolonging overall treatment time and subsequent radiation induced lung fibrosis.
decreases local control

46.5.3 R
 TOG clinical grading scale
46.5 Radiation Pneumonitis of Radiation Pneumonitis

The alveolar epithelium consists of 2 types of • Grade 1: Presence of mild dry cough not
cells, type 1 and type 2 pneumocytes. Type 1 cov- requiring medications
ers about 90% of alveolar surface [2]. The most • Grade 2: Presence of cough requiring narcotic
radiosensitive part of the lung is the alveolar-­ anti-tussives or dyspnea present not at rest
capillary complex. • Grade 3: Severe cough not controlled by
Radiation induced lung injury occurs in two drugs/dyspnea present at rest
different phases: • Grade 4: Patient requiring continuous oxygen
or assisted ventilation to maintain oxygenation
1. Early (<6 months)—radiation pneumonitis
2. Late (>6 months)—radiation induced lung Radiation pneumonitis is a diagnosis of exclu-
fibrosis sion, by excluding other causes. Patient presents
with dry cough, low grade fever, and shortness of
breath. History is very important to find the clue
46.5.1 Risk Factors about the temporal association between of start
of treatment and development of respiratory
1. Patient factors: Age more than 65 years, poor symptoms.
pulmonary function (FEV1 and DLCO) prior
to radiotherapy
2. Smoking 46.5.4 Investigations
3. Mid and lower lobe tumors—higher risk due
to increased oxygen free radical production • Throat swab, sputum culture/sensitivity and
4. RT volumes technique (e.g., active breath AFP
holding, breath holding, etc.) • Chest X-ray
5. Use of concurrent chemotherapy • CT chest: Changes usually limited to areas of
6. Higher serum TGF B1 associated with devel- irradiation/radiation portals
opment of pneumonitis, similarly elevated
levels of IL 1a and IL 6 before, during, and Radiological grading of radiation pneumonitis
after radiation treatment correlate with the is given in Table 46.4
development of radiation pneumonitis
Table 46.4 Grading of radiation pneumonitis
Grade CT Findings
46.5.2 Pathophysiology of Radiation 1 Ground glass opacities without fuzziness of the
Pneumonitis subjacent pulmonary vessels.
2 The findings may vary from ground glass
opacities, extending beyond the radiation field,
Main pathology is the destruction of the type I to consolidation
pneumocytes which starts at 2–4 weeks. The pro- 3 Clear focal consolidation ± elements of fibrosis
duction of cytokines, proteases, and growth fac- 4 Dense consolidation, cicatrization atelectasis,
tors leads to acute pneumonitis. With continued (traction bronchiectasis), significant pulmonary
inflammation, production of reactive oxygen spe- Volume loss and pleural thickening
46 Radiation Toxicity 291

46.5.5 The Differentials radiotherapy. Radiation cystitis is usually sterile

although secondary infections can occur. The
• Disease progression: especially in lung clinical spectrum ranges from asymptomatic
primary hematuria to hemorrhagic cystitis (most severe
• Concomitant infection: high grade fever, pro- clinical manifestation).
ductive sputum, and myalgia may be pointers
toward an infective pathology
• Tuberculosis also needs to be excluded 46.6.1 Risk Factors
• Exacerbation of chronic obstructive pulmo-
nary disease • The incidence of radiation cystitis is directly
proportional to radiation dose and volume of
bladder irradiated.
46.5.6 Management of Radiation • Newer techniques like intensity modulated
Pneumonitis radiotherapy (IMRT) and image guided radio-
therapy (IGRT) reduce the bladder dose as
1. Steroids; oral prednisolone 1 mg/kg (max- well as volume of normal bladder irradiated,
60 mg) for a period of 2 weeks usually pro- thereby reducing the risk of RC.
duces symptomatic benefit. Steroids form the • Concurrent use of chemotherapy like ifos-
mainstay of treatment of radiation pneumoni- famide increases risk of RC.
tis; steroids must be tapered slowly over • Age of patient: Some studies have reported
6 weeks. increased incidence of cystitis in patients
2. Pentoxifylline reduces risk of lung fibrosis. more than 60 years. (1.9%), respectively.
Usually started at 400 mg thrice daily and
continued for of 2 weeks in patients with radi-
ation pneumonitis. 46.6.2 Pathogenesis of Cystitis
3. ACE inhibitors, Enalapril—definite evidence
is lacking. Radiation causes single and double stranded
4. Other supportive measures including treat- DNA breaks leading to both gene repair and
ment of concurrent infection as needed. apoptosis. Endarteritis also occurs which leads to
compromised blood supply and inadequate sup-
Management of radiation induced lung fibro- ply of nutrients to bladder tissue.
sis: The management for established fibrosis is
difficult with no standard guidelines. Options
include: 46.6.3 Symptoms and Work Up

1. Supportive management and clearance of air- • Radiation cystitis can occur up to years after
way secretions radiation and there is no definite time frame.
2. Anti-inflammatory therapy: Corticosteroids • Patients typically present with hematuria, dys-
although are the mainstay of management in uria, frequency and hesitancy, and sometimes
acute radiation pneumonitis their role in retention secondary to blood clots obstructing
established lung fibrosis is not clear the urethra.
3. Treatment of concurrent infection • If the patient presents with hematuria, urinary
calculi, tumors, infections need to be excluded.
• Urine routine and cytology along with blood
46.6 Radiation Cystitis counts is needed.
• Cystoscopy aids in diagnosis and in removing
Radiation cystitis (RC) involves inflammation of clots. Cystoscopy also helps in treatment like
bladder occurring as a complication of pelvic formalin instillation.
292 S. Mallick et al.

Table 46.5 Grading of radiation cystitis sion. These treatment modalities have to be used
Acute genitourinary Chronic genitourinary judiciously for the treatment of radiation
toxicity toxicity cystitis.
Grade I—increased Grade I—micro
frequency of urine hematuria, mild • Discontinuation of any anti-coagulant if
telangiectasia
Grade II—frequency of Grade II—increased
patient is using.
urination > 1 h/pain frequency, generalized • Serial hemoglobin monitoring and blood
requiring local analgesics telangiectasia, intermittent transfusion as needed.
gross hematuria • Saline bladder irrigation: Continuous bladder
Grade III—frequency of Grade III—severe irrigation and clot removal forms the initial
urination < 1 h/pain increased frequency,
requiring narcotic severe telangiectasia, treatment. Urokinase is secreted by kidneys,
analgesics frequent hematuria which can lead to continued bleeding, and
Grade IV—obstruction/ Grade IV—hemorrhagic continuous bladder irrigation removes uroki-
ulcer/necrosis, hematuria cystitis, ulcer/fistula, nase and thus helpful.
requiring transfusions bladder capacity <100 ml
• Intravesical formalin instillation has a success
rate of up to 90%. The main mechanism is
• Imaging—CT and USG may be helpful in precipitation of cellular proteins of bladder
selected cases. mucosa. Concentrations of 1–10% have been
used and a contact period of 3–30 min is usu-
Grading: Radiation Therapy Oncology Group ally recommended.
for radiation cystitis is summarized in Table 46.5. • Alum (1%) irrigation: Acts by protein precipi-
tation leading to vasoconstriction and reduc-
tion in edema and inflammation. Bladder
46.6.4 Prevention irrigation with alum with up to 30 liters has
been used. Alum irrigation is more safe and
There is no preventive modality to decrease the cheaper than formalin. But there are reports of
incidence of radiation-induced hemorrhagic cys- renal impairment with the use of alum.
titis except better radiation planning. Maintaining • Aminocaproic acid acts as a plasminogen acti-
the bladder dose within tolerable limit and mini- vator inhibitor and counteracts the effect of
mizing volume irradiated are the key to preven- urokinase, thus reduces bleeding.
tion of radiation cystitis. • Hyperbaric oxygen is highly effective espe-
cially in refractory cases. It acts by reducing
• Acceptable tolerance depends on primary neovascularization, enhancing granulation tis-
tumor irradiated and dose. Common dose lim- sue formation, and optimizing immune
its may be V65 < 50%, V70 < 35%, V75 < 25%, function.
and V80 < 15% • Nd: YAG laser coagulation results in thermal
• Steroids, vitamin E, trypsin, and orgotein— coagulation of bleeding mucosa. It is highly
Tried but no clinically significantly benefit has effective in control bleeding with success rates
been reported more than 90%. Rare cases of bladder perfora-
tion have been reported.
• Internal iliac artery embolization: Reserved
46.6.5 Treatment for patients who do not respond to other con-
servative approaches. Gangrene of the blad-
Treatment options for hemorrhagic cystitis der, neurological deficit of lower limbs have
include continuous bladder irrigation, instillation been rarely reported.
of alum or formalin, hyperbaric oxygen therapy, • In refractory cases urinary diversion and cys-
embolization, and cystectomy with urinary diver- tectomy remain the only treatment option.
46 Radiation Toxicity 293

46.7 Radiation Proctitis • Grade II—Presenting with moderate diarrhea

and colic, bowel frequency > 5 times per day,
Radiation proctitis (RP) is one of the long term excessive rectal mucus or intermittent
complications that occurs following pelvic radia- bleeding
tion especially in malignancies like cervix and • Grade III—Presenting with obstruction or
prostate which requires relatively higher dose for bleeding that requires surgery
local control. The patient usually presents with • Grade IV—Presence of necrosis, fistula, or
blood in stools or altered bowel habits. perforation

46.7.1 Risk factors 46.7.4 Prevention

Pathophysiology of radiation proctitis is similar Prevention is the most important aspect in the
to radiation cystitis although threshold level is management of RP. Maintaining the rectal dose
lower than that for the development of radiation within tolerable limit and minimizing volume
cystitis. Endarteritis is the primary pathology. irradiated are the key. The use of image guidance
Incidence of radiation proctitis varies from 2 to and IMRT usually helps in maintaining rectal
39% in historical series with the incidence reduc- dose within tolerable limit.
ing with the advent of latest radiation delivery Acceptable tolerance limits may be
techniques like IMRT. Acute radiation proctitis is V50 < 50%, V60 < 35%, V65 < 25%, V70 < 20%,
defined as development of symptoms within and V75 < 15%.
3 months of treatment completion while chronic
occurs more than 3 months.
46.7.5 Treatment

46.7.2 Symptoms and Work Up Acute form is usually self-limiting and improves
on treatment interruption. The supportive mea-
• Symptoms can occur after months or years sure that may be used includes anti-inflammatory,
after radiation. antidiarrheal, hydration and steroid or
• Patients typically present with hematochezia. 5-­aminisalicylic acid enema is required.
• Other symptoms include abdominal pain, Chronic proctitis requires the exclusion of
tenesmus, vomiting, diarrhea. other causes which can present with similar clini-
• Other causes of hematochezia to be ruled out cal picture like infection or inflammatory bowel
are infection or inflammatory bowel disease. disease. Patients with inflammatory bowel dis-
• Stool routine examination. ease are also at an increased risk of developing
• Complete blood count and coagulation radiation proctitis.
parameters. Non-invasive treatment option includes
• Colonoscopy or sigmoidoscopy—presence of NSAIDs, anti-oxidants, sucralfate, short chain
friability and telangiectasia is suggestive of fatty acids, and hyperbaric oxygen.
RP. Helps in diagnosis and treatment. Invasive treatment consists of ablative proce-
• Imaging—CT required in selected conditions. dures like formalin application, endoscopic YAG
laser coagulation, or argon plasma coagulation
and surgery as a last resort as in patients with RC.
46.7.3 Grading
• Formalin instillation—Mechanism of action
• Grade I—Presenting with mild diarrhea or of formalin instillation is same as in the treat-
cramping, bowel frequency < 5 times per day, ment of radiation cystitis. It is used either as 4
mild bleeding or 10% solution and a contact period of
294 S. Mallick et al.

2–3 min is advocated. Perianal skin needs to and series organ. For example, injury to a small
be protected to prevent stricture and skin dam- part of myocardium may be asymptomatic and
age that can be caused by contact with forma- goes unnoticed while injury to a small segment of
lin. Rare side effects include bleeding, coronary arteries or the conducting system may
perforation, and fistulas. be dangerous and life threatening.
• Hyperbaric oxygen (HBO)—HBO is also an Presentation of acute RIHD may range from
effective modality in management of RP, asymptomatic involvement to acute pericarditis.
especially in patients not responding to con- The acute phase is mediated by tumor necrosis
servative management. Availability is one of factor (TNF), and interleukins (IL) IL-1, 6, and 8
the major limitations for its use. further leading to neutrophil infiltration. The
• Laser coagulation—YAG laser coagulation acute effects are usually self-limiting and respond
and argon plasma laser coagulation are also well to conservative management.
one of the options in patients not responding Chronic RIHD is the more important clini-
to conservative management. Patients usually cally than acute RIHD. The pathogenesis is
require 2–3 sessions. Response rate as high as mediated by inflammatory mediators such as
75–80% has been reported. The rare but fatal IL-4, IL-13, and TGF-β which lead to changes
complications include incontinence and rectal leading to fibrosis. Pathological examination
ulceration. shows inflammatory cells, fibroblasts, and colla-
• Surgical treatment—Fecal diversion with gen deposition. Radiation induced fibrosis of the
either colostomy or ileostomy is reserved as a myocardium ultimately leads to decrease in elas-
last resort in non-responding patients. ticity and distensibility, thus leading to reduction
in ejection fraction and cardiac failure. Another
mechanism for chronic RIHD is accelerated ath-
46.8  adiation Induced Heart
R erosclerosis in the medium to large coronary
Disease arteries leading to infraction like changes. Sub-
endothelial fibrosis leads to vascular injury in
Radiation induced heart disease (RIHD) is one of small coronary arteries which can lead to isch-
the late and important but often overlooked com- emia and arrhythmias due to involvement of vas-
plication of radiotherapy for mediastinal lym- cular supply to the conducting tracts or nodes.
phoma, breast, lung, and esophageal cancer. Chemotherapy also contributes to develop-
RIHD is often aggravated with the addition of ment of cardiac disease in cancer patients.
chemotherapy especially anthracyclines used for Anthracyclines and trastuzumab are also impor-
treatment of breast and lymphomas. One of the tant and may have synergistic effect to radiation
reasons why RIHD has not been extensively stud- in development of heart disease. The develop-
ied is the long latent period for the development ment of transtuzumab is more acute than radia-
of RIHD. RIHD includes a spectrum of cardio- tion induced heart failure and can occur during
vascular complication ranging from subclinical treatment.
asymptomatic microscopic changes in heart to
overt heart failure. The most common cardiac
complication to radiotherapy is pericardial (rang- 46.8.2 Diagnosis
ing from asymptomatic pericardial effusion to
constrictive pericarditis), and conduction abnor- Diagnosis of RIHD is often challenging and usu-
malities are the least common. ally is a diagnosis of exclusion of common causes
like ischemic and hypertensive heart disease. A
good clinical examination and prompt investiga-
46.8.1 Pathogenesis tions including ECG, 2D Echo must be done. The
knowledge about latent period for development
RIHD can be acute or chronic effects on heart. of RIHD is also important (takes 10–15 years) for
Radiobiologically heart acts both as a parallel the diagnosis of RILD.
46 Radiation Toxicity 295

Prevention: Dose constrains that need to be anti-arrhythmic. Clinical features and treatment
kept in mind are Mean Dose < 26 Gy. Other con- options are summarized in Table 46.6.
strains that can be kept are V40 < 30%,
V30 < 40%, V20 < 50%, and D MAX of 60 Gray.
46.9 Radiation-Induced Liver
Disease
46.8.3 Management
Radiation-induced liver disease (RILD) is a sub-­
The tolerance, clinical symptoms management, acute form of liver injury due to radiation and is
and prognosis depend on the tissue that is affected of upmost importance in patients planned for
by RIHD. The symptoms and signs depend on radiation therapy for hepatobiliary or upper gas-
the tissue involved and there are no specific trointestinal malignancies [3]. The better knowl-
symptoms specific to identify RIHD. The patient edge of tolerance of liver and better investigations
needs to be managed by an expert cardiologist. to document functional reserve along with mod-
Pericardial disease: Pericardial disease is the ern radiation delivery techniques have greatly
most common manifestations of RIHD and reduced the incidence of RILD.
occurs if a significant proportion of heart (>30%)
receives a dose of 50 Gy. The latent period for Patho-Physiology Retrograde congestion of
development of pericarditis is approximately the liver is the main pathology that occurs in the
1 year. Acute pericarditis is rare and develops development of RILD. These abnormalities of
during or after radiation. Sign and symptoms RILD are similar to that for veno-occlusive dis-
may include fever, chest pain, and pericardial ease and are predominantly evident around the
rub. Acute pericarditis usually resolves by itself central vein. The microscopic changes include
and few patients require supportive measures like endothelium swelling, terminal hepatic venule
NSAIDs. Pericardial effusion usually does not narrowing, sinusoidal congestion, parenchymal
require drainage if asymptomatic and drainage is atrophy of zone, and proliferation of collagen.
needed if patients present with tamponade. Transforming growth factor-beta 1 (TGF-beta
Myocarditis and cardiomyopathy: Myocarditis 1) may of prime importance in the development
risk usually begins to increase after 5 years of of RILD.
radiotherapy and the main pathology is microvas- Radiobiologically liver parenchyma has paral-
cular injury. Most of the patients present with lel architecture in which individual functional
exercise intolerance and reduction in left ventric- units work independently, thus allowing smaller
ular ejection fraction (EF). Treatment usually volumes to receive high-dose as long as the mean
requires ACE inhibitors, angiotensin receptor dose the normal liver is kept within tolerance
blocker, aldosterone antagonist, and limit.
beta-blockers.
Coronary artery disease: Radiation induced
coronary artery disease begins to increase 46.9.1 Risk Factors
10 years after radiation and is progressive with
time. Even though rare this is one of the most • Radiation Dose: RILD incidence is about
fatal complications following radiation to heart. 5–10% when the whole of liver is treated to
Exact mechanism is unknown. Management of 30–35 Gy. Mean dose of 30 Gy is usually
radiation induced CAD is same as in non-­ considered as safe tolerance limit to liver.
radiation related CAD. Patients with deranged liver function are
Arrhythmias: Arrhythmias are a rare compli- more susceptible for development of RILD
cation of RIHD. Fibrosis of myocardium may be and a lower threshold for liver tolerance
the primary mechanism for conduction abnor- needs to be applied for these patients. With
malities following radiotherapy. The manage- the more availability conformal image
ment is mainly medical including use of guided radiotherapy these constraints are
296 S. Mallick et al.

Table 46.6 Clinical features and treatment options in radiation-induced heart disease
Syndromes Clinical Features Investigations Treatment
Acute pericarditis Fever, chest pain and ECG • Self-limiting
pericardial rub 2D-Echo • Bed rest
Investigations to rule out other • NSAIDs
causes-TB, SLE etc. • Diuretics
Chronic pericarditis and Dyspnea, ECG • Loop diuretics
Tamponade Low blood pressure 2D-Echo • Pericardiocentesis
and weak pulse Chest X-ray • Pericardiectomy
Elevated JVP CECT chest
Needle Pericardiocentesis
Cardiomyopathy and Dyspnea ECG • Loop diuretics
CHF Fatigue and weakness 2D-Echo • ACE inhibitors
Edema Cardiac enzymes • Nitro-glycerine
Pulmonary Edema • Vasodilators
• Inotropic agents
Coronary artery disease Chest pain or ECG • Anti-platelets
heaviness 2D-Echo • ACE inhibitors,
Dyspnea Angiography Beta blockers
Fatigue and weakness Cardiac enzymes • Dilatation
• Stents
• Coronary artery
bypass graft
Conduction abnormalities Palpitations ECG • Antiarrhythmic
Dizziness Holter monitoring drugs
Shortness of breath 2D-Echo • Antiplatelet drugs
Chest discomfort or • Pacemaker
pain placement
• Catheter ablation

usually achievable. Dose per fraction is Prevention: There are no effective treatment
another important factor to the development strategies in the management of RILD, and pre-
of RILD and liver is more sensitive to hypo- vention must be of prime importance. Proper
fractionated and accelerated radiotherapy assessment of the patient including functional
than that of conventional schedule. liver reserve is very important.
• Baseline liver status: The baseline liver func-
tion is an important factor in development of • The use of image guidance and respiratory
RILD and background hepatic cirrhosis may motion management techniques (abdominal
be a major risk factor. The Child-Pugh Grading compression, shallow breathing, breath hold-
may be helpful in assessing the baseline liver ing, gating, and tracking) helps in reducing the
function. PTV margins and thus the target volume.
• Chemotherapy and hepatotoxic drugs: • Keeping the tolerance limit is also of prime
Hepatotoxic chemotherapy may be additive to importance.
radiotherapy in development of RILD. The • Animal studies have shown that the use of
treating physician must take into consider- amifostine protects hepatocytes from ionizing
ation the concurrent use of chemotherapy and radiation without compromising tumor cell
other hepatotoxic drugs. kill, but good human data is lacking.
• Other risk factors: Prior transcatheter arterial • Dose constrains: The mean dose to the liver
chemoembolization (TACE), patients with has to be kept less than 32 Gray and the V30
primary hepatobiliary malignancies. must be kept <60%.
46 Radiation Toxicity 297

46.9.2 Clinical Features 46.9.3 Treatment

and Investigations
There are no specific guidelines for the treatment
• Symptoms of RILD occur 2–8 weeks after of RILD, and no therapy has shown to modify the
completion radiotherapy natural course of the disease. Treatment is mainly
• Clinical features are like hat of veno-occlusive directed at control of symptoms and includes:
disease—fatigue and right upper quadrant
pain, massive ascites, and hepatomegaly • Diuretics for fluid retention
• Jaundice is unlikely. Cholangitis may be • Paracentesis for ascites
one of the differentials in addition to disease • Correction of coagulopathy
progression in patients presenting with • Anticoagulants and thrombolytics if hepatic
jaundice vein thrombosis
• Patients usually present with raised alkaline • Steroids to reduce hepatic congestion
phosphatase and transaminitis. Alkaline
­phosphatase usually increases to more than
two times the normal level References
• Viral markers, serum protein and prothrombin
time must also be measured 1. Mallick S, Benson R, Rath GK. Radiation induced
• Ultrasound of the abdomen—ascites and oral mucositis: a review of current literature on pre-
vention and management. Eur Arch Otorhinolaryngol.
hepatomegaly 2016;273(9):2285–93.
• Magnetic resonance imaging—low signal 2. Giridhar P, Mallick S, Rath GK, Julka PK. Radiation
intensity on T1-weighted images and high sig- induced lung injury: prediction, assessment
nal on the T2 and management. Asian Pac J Cancer Prev.
2015;16(7):2613–7.
• Cytopathologic evaluation of the ascitic fluid 3. Benson R, Madan R, Kilambi R, Chander S. Radiation
to rule out malignancy induced liver disease: a clinical update. J Egypt Natl
• Liver biopsy—may help confirm diagnosis Canc Inst. 2016;28(1):7–11.
 Cancer in India
47
Supriya Mallick, Chitresh Kumar, Rony Benson,
and Goura K. Rath

The incidence of cancer has been on an increas- Population Based Cancer Registries [PBCR]
ing trend in India as in the rest of the world. represent different geographical regions in India
Changes in the lifestyle, food habits and and covers approximately 10% of the Indian
increased life expectancy are the major factors population.
that contribute to the increased incidence [1].
The National Cancer Registry Programme was
initiated by Indian Council of Medical Research 47.1 Worldwide Facts
[ICMR] in 1981 with the aim of collecting data
on cancer incidence. The program started with • 60 lakh deaths per year worldwide—12 per-
three population based cancer registries at cent of all deaths
Bangalore, Chennai, Mumbai and three hospital- • Second leading cause of death in the devel-
based cancer registries at Chandigarh, Dibrugarh oped countries—25 lakh cases of deaths per
and Thiruvananthapuram [2]. As of 2018, there year
are 31 Population Based Cancer Registries and • Third leading cause of death in the developing
29 Hospital Based Cancer Registries under countries—38 lakh cases of deaths per year
National Cancer Registry Programme. The • Projected WHO estimates about cancer
deaths world wide—by the year 2020–100
lakh/year
S. Mallick (*)
Department of Radiation Oncology, National Cancer
Institute-India (NCI-India), Jhajjar, Haryana, India 47.2 Cancer Burden in India
C. Kumar
Department of Surgical Oncology, National Cancer The latest publication on cancer incidence by
Institute-India (NCI-India), Jhajjar, Haryana, India
ICMR was published in May 2016. In males,
R. Benson lung cancer is the leading site in 11 registries and
Department of Medical Oncology, RCC,
Thiruvanthapuram, India
breast cancer is the leading site amongst females
in 19 registries. The northeast registries reported
G. K. Rath
Dr. B.R. Ambedkar Institute-Rotary Cancer Hospital,
high burden of tobacco related sites of cancer
All India Institute of Medical Sciences, while highest burden of childhood cancers was
New Delhi, India in Delhi urban registry. Estimated incidence of

© Springer Nature Singapore Pte Ltd. 2020 299

S. Mallick et al. (eds.), Practical Radiation Oncology,
https://doi.org/10.1007/978-981-15-0073-2_47
300 S. Mallick et al.

various cancers is summarised in Tables 47.1, References

47.2 and 47.3 [3].
Population Based Cancer Registries although 1. Murthy NS, Rajaram D, Gautham MS, Shivaraj
NS, Nandakumar BS, Pruthvish S. Risk of can-
represent only 10% of the Indian population, give cer development in India. Asian Pac J Cancer Prev.
us very useful information on cancer incidence, 2011;12(2):387–91.
trend and mortality. The information obtained 2. Rath GK, Gandhi AK. National cancer control and
from these cancer registries is very important in registration program in India. Indian J Med Paediatr
Oncol. 2014;35(4):288–90.
planning and evaluating cancer control 3. NCDIR, Indian Council of Medical Research. Annual
­programmes and thus helps in reducing cancer report (2016–2017) WWW page. http://www.ncdirin-
burden and mortality in the country. dia.org. Accessed 14 Feb 2019.

Table 47.1 Estimated burden in India, PBCR report

New cancer 2016 2020
All sites 14.5 17.3
Breast 1.5 1.9
Lung 1.14 1.4
Cervix 1.0 1.0
Death 7.36 8.8

Table 47.2 Cancer incidence variation in India

Registry Incidence male Registry Incidence female
Aizwal district 270.7 Papumpare district 249
Papumpare district 230.4 Aizwal district 207
East Khasi Hill district 218.3 Kamrup Urban district 174
Mizoram state 211.5 Mizoram state 165.8
Kamrup Urban district 206 Delhi 144.8
Mizoram excl. Aizwal 175 Mizoram excl. Aizwal 136.6
Meghalaya 169.6 Chennai 126.2
Delhi 149.4 Bangalore 125.9
Thiruvananthapuram 132 Thiruvananthapuram 120.4
Nagaland 125.8 Mumbai 118.5
Barshi expanded 40.9 Barshi expanded 52.0

Table 47.3 Sexwise cancer incidence in India

Male Female
Subsite Registry Incidence Registry Incidence
Tongue East Khasi Hill district 11.7 Bhopal 3.7
Oesophagus East Khasi Hill district 71.2
Stomach Papumpare district 50.2 Papumpare district 29.2
Gall bladder Kamrup urban district 17.1
Lung Aizwal district 37.9 Aizwal district 40.8