PRINCIPLE AND CONCEPTS

IN CANCER CARE
Introduction
 The Kenya Health Policy 2012-2030 aims to
attain the highest possible standards of
health that meets the health needs of the
population.
 One of the strategic objectives of this policy
is to reverse and halt the rising burden of
NCDs
 Currently NCD cause over 63% of deaths
globally, with 80% of them occurring in
developing countries
 In Kenya NCD account for more than 50%
of all hospital admissions and over 55% of
hospital deaths
Introduction
 Cancer is one of the four major NCDs.
 Cancer is a generic term for a group of
diseases characterized by the growth and
spread of abnormal cells beyond their usual
boundaries thus invading adjoining parts of the
body and/or spread to other organs.
 Cancer arises from the transformation of
normal cells into tumour cells in a multistage
process that generally progresses from a pre-
cancerous lesion to a malignant tumour
 Cells lose their normal growth controlling
mechanism hence the growth of cells is
uncontrolled
 Introduction
 Cancer cells can move from their original
location to other sites (metastasis)
 It is a leading cause of death globally
accounting for 13% of global mortality.
 In Kenya, cancer is the second leading cause
of NCD related deaths accounting for 7% of
overall national mortality
 The annual incidence of cancer was estimated
at 44,726 new cancer cases, with an annual
mortality 29,317 in 2022.
 Leading cancers in Kenyan women include
breast, cervix and oesophagus while in men
prostrate, oesophagus and colorectum
 Routes of metastasis
 Local seeding: distribution of shed cancer cells
occurs in the local area of the primary tumor.
It can be through the body wall into the
abdominal and chest cavities (transcoelomic).
 Blood borne metastasis: tumor cells enter the
blood, which is the most common cause of
cancer spread.
 Lymphatic spread: primary sites rich in
lymphatics are more susceptible to early
metastatic spread.
 Routes of metastasis
Common sites of metastasis:
 Breast cancer – bone, liver, brain and lungs
 Lung cancer – brain, bones, liver
 Colorectal cancer – liver, lungs and brain
 Prostate cancer – bone, spine and legs
 Oesophageal cancer – lung, liver, bones, brain
 Cervical cancer – lung, liver, bones, abdomen
Risk factors for cancer
◦ Genetic predisposition
◦ Behavioural risk factors (tobacco use &
exposure, unhealthy diets, physical inactivity,
harmful use of alcohol)
◦ Biological risk factors (overweight, obesity,
age, gender)
◦ Environmental risk factors including exposure
to environmental carcinogens such as
chemicals e.g. asbestos, aflatoxins; radiations
like ultraviolet and ionizing radiations;
infectious agents e.g. viruses and bacteria
human papilloma virus (cancer of the cervix),
hepatitis B and C (cancer of the liver), and
helicobacter pylori (cancer of the stomach).
 Patient Management
 Important information is obtained thru
routine history and physical examination.
 The duration of symptoms may reveal the
chronicity of disease.
 The past medical history may alert the
clinician/physician to the presence of
underlying diseases that may affect the choice
of therapy or the side effects of treatment.
 The social history may reveal occupational
exposure to carcinogens.
Patient Management
 The social history may also reveal habits, such
as smoking or alcohol consumption, that may
influence the course of disease and its
treatment.
 The family history may suggest an underlying
familial cancer predisposition and point out
the need to begin surveillance or other
preventive therapy for unaffected siblings of
the patient.
 The review of systems may suggest early
symptoms of metastatic disease
Diagnosis
 The diagnosis of cancer relies most heavily
on invasive tissue biopsy and should never be
made without obtaining tissue.
 No noninvasive diagnostic test is sufficient to
define a disease process as cancer.
 Although in rare clinical settings (e.g., thyroid
nodules) fine-needle aspiration is an
acceptable diagnostic procedure.
Diagnosis
 Obtaining adequate tissue to permit careful
evaluation of the histology of the tumor, its
grade, and its invasiveness and to yield
further molecular diagnostic information e.g.
the expression of cell-surface markers or
intracellular proteins that typify a particular
cancer, or the presence of a molecular
marker.
Diagnosis
 Sufficient tissue is of value in searching for
genetic abnormalities and protein expression
patterns.
 Such protein expression patterns e.g.
hormone receptor expression in breast
cancers, may aid in differential diagnosis or
provide information about prognosis or likely
response to treatment.
Diagnosis
 Histologically similar tumors may have very
different gene expression patterns, with
important differences in response to
treatment.
 Evidence links the expression of certain genes
with the prognosis and response to therapy
 Such testing requires that the tissue be
handled properly (e.g. immunologic detection
of proteins is more effective in fresh-frozen
tissue rather than in formalin-fixed tissue).
Diagnosis
 An excisional biopsy in which the entire
tumor mass is removed with a small margin of
normal tissue surrounding it.
 Incisional biopsy is the procedure of second
choice. A wedge of tissue is removed, and an
effort is made to include the majority of the
cross-sectional diameter of the tumor in the
biopsy to minimize sampling error.
Diagnosis
 The biopsy techniques that involve cutting
into tumor carry with them a risk of
facilitating the spread of the tumor.
 Fine-needle aspiration generally obtains only
a suspension of cells from within a mass. This
procedure is minimally invasive, and if positive
for cancer it may allow inception of systemic
treatment when metastatic disease is evident,
or it can provide a basis for planning a more
meticulous and extensive surgical procedure.
 Prevention
 Avoidance of known or potential carcinogens
and avoidance or modification of the factors
associated with the development of cancer
cells
 Warning signs of cancer-change in bowel or
bowel habits, any sore that does not heal,
unusual bleeding or discharge, thickening or
lump in breast, indigestion, nagging cough or
hoarseness
Early detection through screening
 Mammography.
 Papanicolaou’s test
 Stools for occult blood
 Sigmoidoscopy/colonoscopy
 Breast self examination
 Testicular self examination
 Skin inspection
 Once the diagnosis of cancer is made, the
management of the patient is best
undertaken as a multidisciplinary
collaboration.
 This involves the primary care physician,
medical oncologists, surgical oncologists,
radiation oncologists, oncology nurse
specialists, pharmacists, social workers,
rehabilitation medicine specialists, and a
number of other consulting professionals
working closely with each other and with the
patient and family.
Cancer and Genetics
 Cancer arises through a series of alterations in
DNA that result in unrestrained cellular
proliferation.
 Most of these alterations involve actual
sequence changes in DNA (i.e. mutations).
 They may arise as a consequence of random
replication errors, exposure to carcinogens
(e.g. radiation) or faulty DNA repair processes.
 Familial clustering of cancers occurs in certain
families that carry a germline mutation in a
cancer gene.
 Classes of Cancer Genes
There are two major classes of cancer genes.
 The first class comprises genes that directly
affect cell growth either positively (oncogenes)
or negatively (tumor-suppressor genes).
 These genes exert their effects on tumor
growth through their ability to control cell
division or cell death (apoptosis).
 Oncogenes are tightly regulated in normal
cells. In cancer cells, oncogenes acquire
mutations that relieve this control and lead to
increased activity of the gene product.
Classes of Cancer Genes
 The normal function of tumor-suppressor
genes is to restrain cell growth, and this
function is lost in cancer.
 The second class of cancer genes, the
caretakers, does not directly affect cell growth
but rather affects the ability of the cell to
maintain the integrity of its genome.
 Cells with deficiency in these genes have an
increased rate of mutations in all the genes,
including oncogenes and tumor-suppressor
genes.
Classes of Cancer Genes
 Tumors are masses of cells and these cells
arise from the normal cells of the tissue in
which the cancer originates.
 Read about cancer predisposition
syndromes and associated genes
Genetic Testing for Familial Cancer
 DNA testing can be done to predict the risk
of cancer in individuals of affected families.
 Once a mutation is discovered in a family,
subsequent testing of asymptomatic family
members is key in patient management.
 Positive test may lead to alteration of clinical
management e.g. increased frequency of
cancer screening and, when feasible and
appropriate, prophylactic surgery.
Genetic Testing for Familial Cancer
 Potential negative consequences of a positive
test result include psychological distress
(anxiety, depression) and discrimination
(insurance, employment).
 Testing should therefore not be conducted
without counseling before and after
disclosure of the test result.
 In addition, the decision to test should
depend on whether effective interventions
exist for the particular type of cancer to be
tested.
Genetic Testing for Familial Cancer
 Genetic cancer testing for some cancer
syndromes has greater benefits than risks,
and is offered to test for various genes
associated with the predisposition to breast
cancer (BRCA1 and BRCA2), melanoma
(p16INK4), and colon cancer (APC and the
HNPCC genes).
 Read about common oncogenes altered in
human cancers
The cell cycle
 It is divided into four phases.
 During M-phase, the replicated
chromosomes are separated and packaged
into two new nuclei by mitosis and the
cytoplasm is divided between the two
daughter cells by cytokinesis.
 The interphase: G1 (gap 1), during which the
cell determines its readiness to commit to
DNA synthesis. Cellular components
required for DNA synthesis are prepared
The cell cycle
 The S phase(DNA synthesis), during which
the genetic material is replicated.
 The G2 phase (gap 2), during which the
fidelity of DNA replication is assessed and
errors are corrected. Synthesis of cellular
components for mitosis takes place
 Read about cell cycle specific drugs
 Extent of Disease
 The first priority in patient management after
the diagnosis of cancer is established is to
determine the extent of disease.
 This is done through a process called staging.
 Staging is used to define the extent of disease
either as localized, as exhibiting spread
outside of the organ of origin to regional but
not distant sites, or as metastatic to distant
sites
Staging of cancer
 Staging classifies the clinical aspect of the
tumor.
 It describes the extent of the tumor, the
extent to which the malignancy has
increased in size, the involvement of regional
nodes and metastatic development.
 Stage 0-carcinoma in situ
 Stage I-tumor limited to the tissue of origin,
localized tumor growth
 Stage II-limited local spread
 Stage III-extensive local and regional spread
 Stage IV-metastasis
 Extent of Disease
 The TNM (tumor, node, metastasis) system by
the International Union Against Cancer and
the American Joint Committee on Cancer
(AJCC).
 The TNM classification is an anatomically
based system.
 Categorizes tumors on the basis of the size of
the primary tumor lesion (T1–4, where a
higher number indicates a tumor of larger
size).
Extent of Disease
 The presence of nodal involvement (usually
N0 and N1 for the absence and presence,
respectively, of involved nodes).
 The presence of metastatic disease (M0 and
M1 for the absence and presence,
respectively, of metastases).
Extent of Disease
 Tumor burden increases and curability
decreases with increasing stage.
 Certain tumors cannot be grouped on the
basis of anatomic considerations. E.g.
hematopoietic tumors like leukemia,
myeloma, and lymphoma are often
disseminated at presentation and do not
spread like solid tumors.
Extent of Disease
 The second major determinant of treatment
outcome is the physiologic reserve of the
patient.
 Physiologic reserve is a determinant of how
a patient is likely to cope with the
physiologic stresses imposed by the cancer
and its treatment.
 Patients who are bedridden before
developing cancer are likely to fare worse,
stage for stage, than fully active patients.
Extent of Disease
 This factor is difficult to assess directly.
 Surrogate markers for physiologic reserve
are used, such as the patient's age or
Karnofsky performance status.
 Older patients and those with a Karnofsky
performance status <70 have a poor
prognosis.
Making a Treatment Plan
 Based on the extent of disease and the
prognosis and in conjunction with the
patient's wishes.
 It is determined whether the treatment
approach should be curative or palliative in
nature.
 For some cancers, chemotherapy or
chemotherapy plus radiation therapy
delivered before the use of definitive surgical
treatment may improve the outcome e.g. in
cases of locally advanced breast, head and
Making a Treatment Plan
 In some cases chemotherapy and radiation
therapy need to be delivered sequentially, and
other times concurrently.
 Surgical procedures may precede or follow
other treatment approaches.
 It is best for the treatment plan either to
follow a standard protocol precisely.
 Other regimen can only be part of an ongoing
clinical research protocol evaluating new
treatments. Ad hoc modifications of standard
protocols may compromise treatment results.
Management of the cancer and treatment
Complications
 Cancer therapies are usually toxic. Therefore
management of both the disease and its
treatment, and the complex psychosocial
problems associated with cancer is
imperative.
 In the short term during a course of curative
therapy, the patient's functional status may
decline.
Management of the cancer and treatment
Complications
 The most common side effects of treatment
are nausea and vomiting, febrile neutropenia,
and myelosuppression.
 A critical component of cancer management
is assessing the response to treatment.
 Careful physical examination in which all sites
of disease are physically measured and
recorded in a flow chart by date.
 Response assessment also requires periodic
repeating of imaging tests that were abnormal
at the time of staging.
Management of the cancer and treatment
Complications
 If repeat imaging tests are normal, repeat
biopsy of previously involved tissue is
performed to assess complete response by
pathologic criteria.
 A complete response is defined as
disappearance of all evidence of disease.
 A partial response as >50% reduction in the
sum of the products of the perpendicular
diameters of all measurable lesions.
Management of the cancer and treatment
Complications
 A Progressive disease is defined as the
appearance of any new lesion or an increase
of >25% in the sum of the products of the
perpendicular diameters of all measurable
lesions.
 Tumor shrinkage or growth that does not
meet any of these criteria is considered
stable disease.
Management of the cancer and treatment
Complications
 Tumor markers may be useful in patient
management in certain tumors.
 Some tumors produce or elicit the
production of markers that can be measured
in the serum or urine.
 Rising and falling levels of the marker are
usually associated with increasing or
decreasing tumor burden, respectively.
 Management of the cancer and treatment
Complications
 Tumor markers are not in themselves
specific enough to permit a diagnosis of
malignancy to be made, but once a
malignancy has been diagnosed and shown
to be associated with elevated levels of a
tumor marker, the marker can be used to
assess response to treatment.
 Diagnosis and treatment of depression are
important components of management.
Management of the cancer and treatment
Complications
 This diagnosis is likely in a patient with a
depressed mood (dysphoria) and/or a loss of
interest in pleasure (anhedonia) for at least 2
weeks.
 In addition, three or more of the following
symptoms are usually present: appetite
change, sleep problems, psychomotor
retardation or agitation, feelings of guilt or
worthlessness, fatigue, inability to
concentrate, suicidal ideation.
Management of the cancer and treatment
Complications
 Patients with these symptoms should receive
therapy.
 Medical therapy with a serotonin reuptake
inhibitor such as fluoxetine (10–20 mg/d),
sertraline (50–150 mg/d), or paroxetine (10–
20 mg/d) or a tricyclic antidepressant such as
amitriptyline (50–100 mg/d) or desipramine
(75–150 mg/d) allowing 4–6 weeks for
response.
 Effective therapy should be continued at least
6 months after resolution of symptoms.
Management of the cancer and
treatment Complications
 In addition to medication, psychosocial
interventions such as support groups,
psychotherapy are beneficial.
Principles of cancer treatment
 The primary goal of cancer treatment is to
eradicate the cancer.
 If that cannot be accomplished, the goal shifts
to palliation, the amelioration of symptoms,
and preservation of quality of life while
striving to extend life.
 When cure of cancer is possible, cancer
treatments may be undertaken despite the
certainty of severe and perhaps life-
threatening toxicities.
Principles of cancer treatment
 The therapeutic index of many interventions
is quite narrow, and most treatments are
given to the point of toxicity.
 Conversely, when the clinical goal is
palliation, careful attention to minimizing the
toxicity of potentially toxic treatments
becomes a significant goal.
 One of the challenges of cancer treatment is
how to use the various treatment modalities
either singly or in combination to maximize
chances for patient benefit.
Principles of cancer treatment
 Cancer treatments are divided into four main
types: surgery, radiation therapy,
chemotherapy and biologic therapy (including
immunotherapy and gene therapy).
 The modalities are often used in combination
 Surgery and radiation therapy are considered
local treatments, while chemotherapy and
biologic therapy are systemic treatments.
Principles of cancer treatment
 Cancer mimics an organ attempting to
regulate its own growth.
 However, cancers do not have a limit on how
much growth should be permitted.
 Normal organs and cancers share the
property of having (1) a population of cells in
cycle and actively renewing and (2) a
population of cells not in cycle.
 In cancers, cells that are not dividing are
heterogeneous; Some are starving for
nutrients and oxygen.
Principles of cancer treatment
 Some have sustained too much genetic
damage to replicate but have defects in their
death pathways that permit their survival.
 Some are out of cycle but poised to be
recruited back into cycle and expand if
needed .
 Severely damaged and starving cells are
unlikely to kill the patient.
Principles of cancer treatment
 The problem is that the cells that are
reversibly not in cycle are capable of
replenishing tumor cells physically removed
or damaged by radiation and chemotherapy.
 The growth fraction of a neoplasm starts at
100% with the first transformed cell and
declines exponentially over time until at the
time of diagnosis.
 Thus, peak growth rate occurs before the
tumor is detectable.
Principles of Cancer Surgery
 Surgery is used in cancer prevention,
diagnosis, staging, treatment (for both
localized and metastatic disease), palliation,
and rehabilitation.
 Prophylaxis: cancer can be prevented by
surgery in people who have premalignant
lesions resected (e.g., premalignant lesions of
skin, colon, cervix) and in those who are at
increased risk of cancer from either an
underlying disease e.g. (in those with
pancolonic involvement with ulcerative colitis)
Principles of Cancer Surgery
 Surgery can also be performed in the
presence of genetic lesions (colectomy for
familial polyposis, bilateral mastectomy or
oophorectomy for familial breast or ovarian
cancer syndromes).
 Diagnosis: the underlying principle in cancer
diagnosis is to obtain as much tissue as safely
possible. Owing to tumor heterogeneity,
pathologists are better able to make the
diagnosis when they have more tissue to
examine.
 Principles of Cancer Surgery
 Sufficient tissue is of value in searching for
genetic abnormalities and protein expression
patterns, such as hormone receptor
expression in breast cancers, that may aid in
differential diagnosis or provide information
about prognosis or likely response to
treatment.
 Staging: defines the extent of disease.
Pathologic staging requires defining the extent
of involvement by documenting the histologic
presence of tumor in tissue biopsies obtained
through surgery
Principles of Cancer Surgery
 Axillary lymph node sampling in breast
cancer and lymph node sampling at
laparotomy for lymphomas and testicular,
colon, and other intraabdominal cancers may
provide crucial information for treatment
planning and may determine the extent and
nature of primary cancer treatment.
 Treatment: surgery is the most effective
means of treating cancer. About 40% of
cancer patients are cured by surgery.
Principles of Cancer Surgery
 A large fraction of patients with solid tumors
(perhaps 60%) have metastatic disease that is
not accessible for removal.
 However, even when the disease is not
curable by surgery alone, the removal of
tumor can obtain important benefits:
◦ local control of tumor
◦ preservation of organ function
◦ debulking that permits subsequent therapy to
work better
◦ staging information on extent of involvement.
Principles of Cancer Surgery
 Cancer surgery aiming for cure is usually
planned to excise the tumor completely with
an adequate margin of normal tissue
 Surgery should touch the tumor as little as
possible to prevent vascular and lymphatic
spread, and minimizing operative risk.
 Advances in adjuvant chemotherapy and
radiation therapy following surgery have
permitted a decrease in the extent of
primary surgery necessary to obtain the best
outcomes.
 Principles of Cancer Surgery
 Lumpectomy with radiation therapy is as
effective as modified radical mastectomy for
breast cancer
 Limb-sparing surgery followed by adjuvant
radiation therapy and chemotherapy has
replaced radical primary surgical procedures
involving amputation and disarticulation for
childhood rhabdomyosarcomas.
Principles of Cancer Surgery
 In some settings, cancers e.g., bulky testicular
cancer or stage III breast cancer—surgery is
not the first treatment modality employed.
 After an initial diagnostic biopsy,
chemotherapy and/or radiation therapy is
delivered to reduce the size of the tumor and
clinically control undetected metastatic
disease.
 Such therapy is followed by a surgical
procedure to remove residual masses; this is
called neoadjuvant therapy.
Principles of Cancer Surgery
 In patients with colon cancer who have fewer
than five liver metastases restricted to one
lobe and no extrahepatic metastases, hepatic
lobectomy may produce long-term disease-
free survival in these patients.
 Surgery is also associated with systemic
antitumor effects. In hormonally responsive
tumors, oophorectomy and/or adrenalectomy
may control estrogen production, and
orchiectomy may reduce androgen
production; both have effects on metastatic
tumor growth.
Principles of Cancer Surgery
 Palliation: surgery is used for supportive care
e.g. insertion of central venous catheters,
control of pleural and pericardial effusions
and ascites, stabilization of cancer-weakened
weight-bearing bones, and control of
hemorrhage, among others.
 Surgical bypass of gastrointestinal, urinary
tract, or biliary tree obstruction can alleviate
symptoms and prolong survival.
Principles of Cancer Surgery
 Surgical procedures may provide relief of
otherwise intractable pain or reverse
neurologic dysfunction (cord decompression).
 Rehabilitation: surgical procedures are also
valuable in restoring a cancer patient to full
health. Orthopedic procedures may be
necessary to assure proper ambulation.
 Principles of Cancer Surgery
 Breast reconstruction can make an enormous
impact on the patient's perception of successful
therapy.
 Plastic and reconstructive surgery can correct
the effects of disfiguring primary treatment.
Principles of Radiation Therapy
 Radiation therapy uses radiation to treat
cancer.
 Radiation is a physical form of treatment that
damages any tissue in its path.
 Radiation causes breaks in DNA and
generates free radicals from cell water that
may damage cell membranes, proteins and
organelles.
 Radiation damage is dependent on oxygen;
hypoxic cells are more resistant.
Principles of Radiation Therapy
 Therapeutic radiation is delivered in three
ways: (1) teletherapy, with beams of radiation
generated at a distance and aimed at the
tumor within the patient; (2) brachytherapy,
with encapsulated sources of radiation
implanted directly into or adjacent to tumor
tissues; and (3) systemic therapy, with
radionuclides targeted to a site of tumor.
 Teletherapy is the most commonly used form
of radiation therapy.
Principles of Radiation Therapy
 X-rays and gamma rays are the forms of
radiation most commonly used to treat
cancer.
 They are both electromagnetic, non-
particulate waves that cause the ejection of
an orbital electron when absorbed. This
orbital electron ejection is called ionization.
 X-rays are generated by linear accelerators;
gamma rays are generated from decay of
atomic nuclei in radioisotopes e.g. cobalt and
radium.
Principles of Radiation Therapy
 These waves behave biologically as packets
of energy, called photons.
 A number of parameters influence the
damage done to tissue by radiation:
◦ Hypoxic cells are relatively resistant.
◦ Non-dividing cells are more resistant than
dividing cells.
◦ The energy of the radiation determines its ability
to penetrate tissue. Low or megavoltage energy
Principles of Radiation Therapy
 Low-energy orthovoltage beams scatter
when they strike the body resulting in more
damage to adjacent normal tissues and less
radiation delivered to the tumor.
 Megavoltage radiation has very low lateral
scatter; this produces a skin-sparing effect,
more homogeneous distribution of the
radiation energy and greater deposit of the
energy in the tumor, or target volume.
Principles of Radiation Therapy
 The tissues that the beam passes through to
get to the tumor are called the transit volume.
 Dose homogeneity in the target volume is
the goal.
 Radiation is quantified on the basis of the
amount of radiation absorbed by the patient
not the amount of radiation generated by
the machine.
 The rad (radiation absorbed dose) is defined
as 100 erg of energy per gram of tissue.
 The SI unit for rad is the Gray.
Principles of Radiation Therapy
 Radiation dose is measured by placing
detectors at the body surface.
 Radiation dose has three determinants: total
absorbed dose, number of fractions, and
time/duration of treatment.
 Most curative radiation treatment programs
are delivered to particular targets once a
day, 5 days a week in 150-to-200 cGy
fractions.
Principles of Radiation Therapy
 Radiation therapy is a curative therapy for
breast cancer, Hodgkin's disease, head and
neck cancers, prostate cancer and
gynecological cancers.
 Radiation therapy can also palliate disease
symptoms in the relief of bone pain from
metastatic disease, control of brain
metastases, reversal of spinal cord
compression and superior vena caval
obstruction, shrinkage of painful masses and
opening of threatened airways.
Principles of Radiation Therapy
 In high-risk settings, radiation therapy can
prevent the development of brain
metastases in acute leukemia and lung
cancer
 Radiation oncologists may administer
radionuclides with therapeutic effects.
 Iodine 131 is used to treat thyroid cancer
since iodine is naturally taken up
preferentially by the thyroid; it emits gamma
rays that destroy the normal thyroid as well
as the tumor.
Principles of Radiation Therapy
 Strontium 89 and samarium 153 are two
radionuclides that are preferentially taken up
in bone, particularly sites of new bone
formation.
 Both are capable of controlling bone
metastases and the associated pain.
 Acute toxicities of radiation therapy include
mucositis, skin erythema and bone marrow
toxicity. These can be alleviated by
interruption of treatment.
Principles of Radiation Therapy
 Chronic toxicities are more serious e.g.
◦ Radiation of the head and neck region often
produces thyroid failure.
◦ Cataracts and retinal damage can lead to blindness.
Salivary glands stop making saliva, which leads to
dental caries and poor dentition.
◦ Taste and smell can be affected.
◦ Mediastinal irradiation leads to a threefold
increased risk of fatal myocardial infarction.
◦ Other late vascular effects include chronic
constrictive pericarditis, lung fibrosis, viscus
stricture, spinal cord transection, and radiation
enteritis.
Principles of Chemotherapy
 Medical oncology is the subspecialty that
cares for and designs treatment approaches
to patients with cancer, in conjunction with
surgical and radiation oncologists.
 They determine those drugs that may have a
beneficial effect on the patient's illness or
favorably influence the patient's quality of
life.
 The curability of a tumor is inversely related
to tumor volume and directly related to
drug dose.
Principles of Chemotherapy
 Chemotherapy agents are used for the
treatment of active, clinically apparent cancer
e.g. leukemias and hodgkins disease.
 If a tumor is localized to a single site,
surgery or primary radiation therapy may be
curative as local treatments.
 Chemotherapy may be used when these
modalities fail to eradicate a local tumor or
as part of multimodality approach to the
primary treatment of a clinically localized
tumor.
Principles of Chemotherapy
 Chemotherapy can allow organ
preservation when given with radiation, as
in the larynx or other upper airway sites; or
sensitize tumors to radiation when given to
patients concurrently receiving radiation for
lung or cervix cancer.
 Chemotherapy can be administered as an
adjuvant i.e. in addition to surgery or
radiation, after all clinically apparent disease
has been removed.
Principles of Chemotherapy
 This use of chemotherapy may have curative
potential as it attempts to eliminate clinically
unapparent tumor that may have already
disseminated.
 Chemotherapy is routinely used in
"conventional" dose regimens.
 These doses produce reversible acute side
effects e.g. transient myelosuppression with
or without gastrointestinal toxicity (usually
nausea), which are readily managed.
Principles of Chemotherapy
 High-dose chemotherapy regimens can
produce markedly increased therapeutic
effect in relapsed leukemias.
 If cure is not possible, chemotherapy may be
undertaken with the goal of palliating some
aspect of the tumor's effect on the host
 (review pharmacology of chemotherapeutic
agents )
Biologic Therapy
 The goal is to manipulate the host-tumor
interaction in favor of the host.
 Many biologic therapies require an active
response (e.g. re-expression of silenced
genes, or antigen expression) on the part of
the tumor cell or on the part of the host (e.g.
immunologic effects) to allow therapeutic
effect.
 The existence of cancer in a person is
testimony to the failure of the immune
system to deal effectively with the cancer.
Biologic Therapy
 Tumors avoid the immune system by:
◦ they are often only subtly different from the
normal cells
◦ they are inefficient at presenting antigens to the
immune system
◦ they can cloak themselves in a protective shell of
fibrin to minimize contact with immune
surveillance mechanisms
◦ they can produce a range of soluble molecules,
including potential immune targets, that can
distract the immune system from recognizing the
tumor cell or can kill the immune effector cells.
Biologic Therapy
 Cancer treatment further suppresses host
immunity.
 Strategies being tested to overcome these
barriers include:
◦ Allogeneic bone marrow transplantation.
Transferred T cells from the donor expand in the
tumor-bearing host, recognize the tumor as being
foreign, and can mediate impressive antitumor
effects
◦ Cytokines like interferon (IFN) , IL-1 to-29; the
tumor necrosis factor. Only IFN- and IL-2 are in
clinical use.
Biologic Therapy
 Interferon induces the expression of many
genes, inhibits protein synthesis and exerts a
number of different effects on diverse
cellular processes.
 Interferon is not curative for any tumor but
can induce partial responses in follicular
lymphoma, hairy cell leukemia, CML,
melanoma, and Kaposi's sarcoma.
Biologic Therapy
 IL-2 exert its antitumor effects indirectly
through augmentation of immune function. It
promotes the growth and activity of T cells
and natural killer (NK) cells.
 High doses of IL-2 can produce tumor
regression in certain patients with metastatic
melanoma and renal cell cancer.