Journal of the ICRU Vol 13 No 1 – 2 (2013) Report 89 doi:10.

1093/jicru/ndw009
Oxford University Press

8. Dose and Volume Parameters for Prescribing, Recording,

and Reporting Brachytherapy, Alone and Combined
with External-Beam Radiotherapy

8.1 Brief Historical Survey of Dose Effects with bio-mathematical models while striving to es-
and Reporting tablish a common terminology and predictors for
outcome. Biological models, applicable to the com-
There are large amounts of accumulated data on
plexity of brachytherapy of the cervix, have been
the effects of radiation on both tumors and normal
implemented in a pragmatic way (see Sections 7.6–
tissues. There has been a long and successful record
7.8). Current planning aims are based on clinical
of curative treatment of cervical cancer applying
experience combined with models to define dose con-
brachytherapy alone for limited disease, or com-
straints. With the introduction of image-guided adap-
bined with external-beam radiation therapy (EBRT)
tive brachytherapy, communication of information
for more advanced disease (see Section 2.9). In the
about absorbed dose, absorbed dose per fraction, and
radium era, absorbed dose in brachytherapy was
absorbed-dose rates to defined volumes in a valid way
specified mainly in terms of the product of the
has become more reliable, thus facilitating a better
radium mass and the treatment time, in units of
understanding of the relationships between absorbed
milligram hours (mg h) (later TRAK) or as absorbed
dose and volume (Pötter et al., 2006).
dose to Point A (see Sections 3.2 – 3.5, 10.1, and
First published experiences with a considerable
11.3). An amount of radium mass times treatment
number of patients treated in a single institution
time, specified in terms of mg h, or absorbed dose to
have shown dose –volume effects based on a volu-
Point A, applied under certain conditions, resulted
metric representation of absorbed dose to the target
in predictable levels of tumor control, survival, and
and OARs, and local control, and normal-tissue mor-
adverse side effects.
bidity (Dimopoulos et al., 2009; Georg et al., 2009;
The rectum, bowel, and bladder were identified as
2012; Koom et al., 2007) (see Figure 8.1).
organs at risk (OAR) of major importance and often
suffered severe radiation-induced inflammatory or
ulcerative disease, sometimes resulting in the devel-
8.2. Dose Distribution and DVH for
opment of fistulae and stenosis. Absorbed-dose as-
Targets and OARs
sessment for the rectum and the bladder was based
mainly on reproducible anatomic or applicator- The heterogeneous absorbed-dose distribution in
related points, which could be defined on orthogonal highly variable volumes, typical of intracavitary
radiographs with the applicator in place (see Section brachytherapy, requires comprehensive assessment.
10.3). Some of these points were later defined as Absorbed doses delivered to different volumes in dif-
ICRU reference points (ICRU, 1985). In particular, ferent locations within different biological systems
the rectum dose – effect relations using these refer- over different time intervals lead to very different bio-
ence points defined 30 years ago are based on large logical effects. Integrated absorbed-dose assessment
multi-center experience (Pötter et al., 2001a; for brachytherapy and for EBRT within a complex 4D
Pourquier et al., 1982). registration system (volume and time) is an enormous
Attempts to relate the more than 50 years of challenge (see Section 8.5) and should ideally take
experience using LDR brachytherapy to the newer into account effects at the cellular level. Simple,
modalities of high-dose rate (HDR) and low-dose rate voxel-based registration methods that do not take
(PDR) brachytherapy required new radiobiological into account spatial volume changes of tumor and
models for predicting tumor and normal-tissue organs are not sufficient.
effects (see Sections 7.6 and 7.7). Radiobiologists The overall aim of dose prescription and reporting is
investigated absorbed-dose-rate effects and tried to to describe the dose distribution related to target
interpret new experimental and clinical information volumes and to OARs as completely and precisely as

# International Commission on Radiation Units and Measurements 2016

 PRESCRIBING, RECORDING, AND REPORTING BRACHYTHERAPY FOR CANCER OF THE CERVIX

possible. The typical heterogeneity of the brachyther- volume histogram (DVH), which provides information
apy absorbed-dose distribution complicates achieve- about volume irradiated as a function of absorbed dose.
ment of this goal. In the hypothetical case of a Recording and reporting the entire DVH for each
completely uniform absorbed-dose distribution over patient might not be practical in summarizing a series
the target volume, there would simply be one dose of patients, and methods to compare different DVHs
value prescribed and reported. Absorbed-dose homo- and link them to dose–volume effects are not straight-
geneity in the target volume has been the major aim of forward. Therefore, single parameters derived from a
most traditional EBRT techniques. However, even cumulative DVH are often used in an attempt to
with external photon beams, it is not possible to predict a certain biological effect. Parameters in the
achieve completely uniform absorbed-dose distribu- form of DV are defined as dose received by at least a
tions. The mean, median, near maximum, and near volume V, where V is given as a percent of a defined
minimum absorbed-dose values serve for reporting region or in units of cm3. Parameters VD are the
realistic absorbed-dose distributions. More information volume receiving doses greater than or equal to the
is conveyed through the entire cumulative dose– absorbed dose D specified either as the absorbed dose,
the EQD2, or a percent of a defined absorbed-dose
value. The DVH parameters should be chosen to
predict outcome with high accuracy.
Examples of DVH are shown in Figure 8.2. The
DVH has a plateau until it reaches the minimum
absorbed dose (the near minimum dose D98%) in the
specified volume. There is then a region of declining
absorbed dose until it reaches the highest absorbed
dose shown on the plot. With brachytherapy, the
absorbed dose near the sources becomes very high, as
shown in Figure 8.2. Organs at risk not containing
sources will fall to zero volume at the maximum
absorbed dose received by that organ.
In situations in which the final slope of the DVH
approximates a straight line, only two numerical
values as D98 % and D2 % would be needed to describe
Figure 8.1. Example of a dose–volume response curve for rectum adequately the DVH. However, for realistic dose dis-
late effects in 141 patients treated with definitive radio-chemotherapy tributions within clinically relevant volumes, more
for advanced cervical cancer and image-guided adaptive
brachytherapy (from Georg et al., 2012). Note that D2cc was a symbol
points are needed for a description that conveys the
previously used for D2cm3 . shape. Sometimes a third point adds the necessary

Figure 8.2. Example of two target DVHs based on typical brachytherapy and EBRT absorbed-dose distributions. The intracavitary
brachytherapy DVH indicates a highly heterogeneous absorbed dose with 98 % of the volume being covered by 7 Gy, and a significantly
higher median absorbed dose of 12 Gy. The EBRT DVH shows an almost flat absorbed-dose profile followed by a steep fall. In this case, 98
% of the volume is covered by 44 Gy, and the median absorbed dose is 45 Gy.

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 Dose and Volume Parameters

information. However, if more points are needed, the curve. It remains difficult to determine exactly which
entire curve should probably be provided. of the DVH parameters is most directly related to a
Because intracavitary brachytherapy is most often particular clinical effect (e.g., is rectal toxicity related
combined with EBRT, when assessing dose to the to a high-dose region as described by the minimum
target and OARs, the integrated EBRT and brachy- dose to 0.1 cm3, 2 cm3, or 5 cm3). However, in order to
therapy dose must be taken into account (see compare DVH parameters for combined EBRT and
Figure 8.3) (in case of midline block see Tamaki et al., intracavitary brachytherapy with DVH parameters
2015). The weighting of EBRT and brachytherapy from other RT techniques, such as interstitial brachy-
doses has major impact on the accumulated dose distri- therapy or external-beam radiotherapy, stereotactic
bution and dose gradients. The dose heterogeneity is radiotherapy, proton, and other particle therapy, it
substantially increased when an increased fraction of may be necessary to report a set of parameters that are
the total EQD2 is delivered by brachytherapy. believed to be most logically linked to a certain clinical
As discussed above, the dose heterogeneity in effect, for example, high-dose levels in small volumes
various volumes will not be fully reflected if only a for bleeding and ulceration. Dose–volume histograms
single point on the DVH is reported, and therefore, het- reduce spatial three-dimensional (3D) information into
erogeneous doses are more adequately described by a 2D dose and volume representation.
choosing a number of appropriate points. In the case of The specific spatial location(s) within a certain
similar steepness and bending of the DVH, which volume of interest is not indicated on the DVH.
occurs for the same combination of EBRT and brachy- However, both targets and OARs often are composed
therapy EQD2, a variety of points on the DVH for a of sub-volumes that have different biological charac-
patient are surrogates for proper estimation of the full teristics, function, and response to dose. For example,

Figure 8.3. Dose profiles from intracavitary brachytherapy and whole-pelvis EBRT. (Upper left) The EBRT covers the elective CTV-E with
a homogeneous absorbed dose, whereas the brachytherapy boost presents with the typical inhomogeneous absorbed dose; lateral EBRT
(dashed line) and brachytherapy (solid line) absorbed-dose profiles (relative absorbed dose normalized to prescribed EBRT and
brachytherapy dose, respectively). (Upper right and lower panel) Accumulated EBRTþbrachytherapy dose in EQD2 (a/b ¼ 10 Gy inside
the CTV, and a/b ¼ 3 Gy outside the CTV) in lateral and anterior–posterior directions, respectively. In the anterior–posterior direction,
the steep dose increase at the border of the CTVHR is due to the change in a/b from tumor to normal tissue. Red dashed lines indicate
EQD2 dose levels of 85 Gy and 45 Gy.
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 PRESCRIBING, RECORDING, AND REPORTING BRACHYTHERAPY FOR CANCER OF THE CERVIX

certain regions of the tumor are likely to benefit from Section 10.1.2 and Figure 10.2). Point A is now
a higher dose because of clonogenic cell density or a defined in a fixed relationship to the applicator, 2 cm
specific micro-environment (e.g., hypoxia). Similarly, cranial to the upper surface of the vaginal applicator
the functionality of OAR has some spatial distribu- part (see Section 10.1.1) and at a distance of 2 cm
tion, such as for the bladder where the trigonum/ left and right lateral to the intrauterine tandem ap-
bladder neck has a specific bladder emptying func- plicator. Dose to Point A is a surrogate for the
tion. Therefore, a specific dose distribution in a spe- minimum target dose in a symmetrical cylindrical
cific volume is expected to influence the outcome, and target volume with a diameter of 4 cm and a height
there will be an inherent limitation in the use of DVH less than the loaded part of the tandem. The total
alone. Sub-volumes can be delineated to focus on a equieffective dose at Point A delivered through
certain biological target and clinical effect, and conse- EBRT and brachytherapy can be calculated using
quently, the calculation of DVHs for such sub- the EQDX concept. Reporting of the dose to Point A
volumes might be used for further characterization of is not dependent on target-volume contouring, and
the dose distribution. However, the most appropriate therefore is a key parameter that allows a direct
method remains the study of the entire spatial comparison of the effects of dose delivered to differ-
absorbed dose and EQD2 distribution within the ent patients in different departments with different
target and OAR volumes, usually performed by dis- fractionation schedules and absorbed-dose rates.
playing the isodose distributions slice-by-slice. For intracavitary brachytherapy, isodose lines at
distances of 2 cm from the tandem already exhibit
smooth contours. This is substantially different from
8.3. Point Doses and Dose –Volume the situation in which intracavitary brachytherapy is
Parameters for the Target combined with interstitial implants. In this case,
Point A is located within a region of a very heteroge-
8.3.1 TRAK and Dose to Point A
neous absorbed-dose distribution, depending on each
In the past, dose assessment for brachytherapy was single dwell position within a needle. A dwell position
mainly based on the amount of radiation incident on could even be exactly at Point A, resulting in an in-
the patient (TRAK) and/or the absorbed dose at speci- definable absorbed-dose value. For such cases, the
fied points, such as Point A (see Sections 3.2, 3.4, absorbed dose to Point A does not represent a rele-
10.1.1, and 11.3). A large clinical experience has and is vant target absorbed dose, and Point A cannot be
still being accumulated with these metrics worldwide. used for reporting. If the interstitial component is
The continuation of their use makes it possible to limited to one lateral part of the implant, the
build upon previous experience and to facilitate com- absorbed dose to Point A on the contralateral side can
munication between current radiographic-based and be used for dose evaluation during treatment plan-
the volume-image-based radiotherapy approaches. ning (see clinical examples in the Appendix).
The TRAK is the integral of the reference air-
kerma rate from all sources at a distance of 1 m from
8.3.2 CTVHR and CTVIR (D98 %, D90 %, D50 %)
the source over the treatment duration (for details,
see Section 11.3). The concept of a product of source The GEC ESTRO report recommended the reporting
strength and treatment time is, in principle, very of D100 % and D90 %, defining the minimum doses deliv-
similar to reporting radium treatments in units of ered to 100 % and 90 % of the target volume, respect-
mg h. It is linked approximately to the integral ively. These DVH parameters reflect the dose in the
absorbed dose delivered to the patient. TRAK is a outer region of the target. D90 % is more stable with
purely physical parameter and cannot be directly respect to random uncertainties when compared with
associated with a given biological effect because an absolute minimum target dose, D100 %. However,
TRAK does not take into account the absorbed-dose due to the significant absorbed-dose gradients, D90 %
distribution, fraction size, and absorbed-dose rate. might look favorable even though 10 % of the target
For example, the TRAK required for a PDR treatment volume receives a much lower dose. The minimum
schedule will be higher than for an HDR treatment target absorbed dose is very dependent on volume re-
because a PDR treatment usually produces lower bio- construction and absorbed-dose sampling in the treat-
logical effects per unit TRAK than does an HDR ment–planning system (ICRU, 2010; Kirisits et al.,
treatment. TRAK, without any further radiobiologic- 2007). A more robust metric is the near-minimum dose
al normalization, can be used only for comparisons D98 %, in which 2 % of the target volume receives less
among treatments with similar equieffective fraction- than this dose. D98 % is also proposed for IMRT treat-
ation schedules (see Section 7). ments in ICRU Report 83 (ICRU, 2010). Because of the
Absorbed dose to Point A is related to the absorbed absorbed-dose gradients in brachytherapy, there can
dose within or close to the target structures (see be considerable differences between D98 % and D100 %

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 Dose and Volume Parameters

(Schmid et al., 2012), and therefore, care must be for intracavitary brachytherapy would represent the
taken when comparing previously reported D100 % dose to tissue close to the source or even in the applica-
values with new D98 % values. The use of D98 % and tor itself and might not be relevant. The use of D98 %,
D90 % parameters is recommended for reporting dose D90 %, and D50 % for intracavitary brachytherapy alone
to the CTVHR. If the CTVIR is used for prescription and could be seen as analogous to the ICRU Report 83
in the case of clinical trials, these two parameters are recommendations to report D98 %, D50 %, and D2 % for
also recommended for the CTVIR. target structures treated with IMRT. However, the
High-dose volumes for intracavitary brachytherapy dose range described with these three parameters is
are regarded as important because they probably con- very different for EBRT combined with brachytherapy.
tribute to the excellent local control observed, even for For IMRT treatment plans, the D98 % and D2 % are
large-volume disease (Viswanathan et al., 2011a). The usually between +10 % of D50 %. The situation is dif-
brachytherapy dose heterogeneity is substantial in the ferent for intracavitary brachytherapy combined with
target region, with typical absorbed-dose gradients of EBRT. The difference depends in particular on the
from 5 % to 25 % mm21, which means that a consider- tumor size and the implant, as well as on the weight-
able part of the tumor will be irradiated to more than ing of EBRT and brachytherapy doses. For convention-
200 % of the absorbed dose to Point A. When taking al treatment schedules in which about half of the
into account fraction size and absorbed-dose rate, the total EQD2 to the primary target is delivered by
heterogeneity of the biologically equieffective dose in brachytherapy, the dose heterogeneity is significant
the target becomes even more pronounced, as the high with D50 %, in terms of total EQD2, being substantially
absorbed doses near the applicator are even more ef- higher than D90 % (see Figure 8.4).
fective because they are delivered at a higher absorbed-
dose rate for LDR treatments and larger fraction size
for HDR treatments (see Section 7.1.1). For the evalu- 8.3.3 GTVres at the Time of Brachytherapy
ation of these high-dose volumes, the DVH parameter (D98 %)
D50 % is recommended. However, because of these high The brachytherapy applicator is generally placed
absorbed-dose values, substantial radiobiological uncer- inside or very close to the residual GTV, and the
tainties are inherent in calculating an EQD2 of D50 % minimum absorbed dose in the GTVres at the time of
(see Section 7.6.4) brachytherapy is often much higher than the
In ICRU Report 83 (ICRU, 2010), the use of the minimum absorbed dose to the CTVHR, which in turn
near-maximum dose D2 % was recommended. A D2 % is very much higher than the minimum absorbed

Figure 8.4. Dose–volume histogram for GTVres, CTVHR, and CTVIR. The initial planning-aim absorbed dose was 25  1.8 Gy
external-beam therapy (44.3 Gy EQD2) plus 4  7 Gy with HDR brachytherapy (40 Gy EQD2) for a total D90 % for the CTVHR of 84 Gy
EQD2 (a/b ¼ 10 Gy). The fraction on the x-axis illustrates the normalized absorbed dose per brachytherapy fraction. *Total EQD2 values
(D98 %, D90 %, and D50 %) are given.

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 PRESCRIBING, RECORDING, AND REPORTING BRACHYTHERAPY FOR CANCER OF THE CERVIX

dose to the CTVIR. D98 % and D90 % are relevant dose dose to the obturator and internal iliac lymph-node
parameters for the GTVres. The equieffective dose cal- regions is about from 15 % to 30 % of the absorbed
culations for D50 % for the GTVres become unreliable dose to Point A, while it is about from 10 % to 20 % in
because they exceed the limits of the models currently the external iliac chain (Gebara et al., 2000; Lee et al.,
in use (see Section 7.6.4). As the experience with dose 2009). In terms of EQD2, this amounts to from 4 Gy
values reported for the GTVres is limited, it is recom- to 8 Gy for obturator and internal iliac nodes and from
mended to keep D98 % as the primary parameter and 2 Gy to 6 Gy for external iliac lymph nodes in HDR
D90 % in the case of research-oriented analysis. brachytherapy schedules with four brachytherapy
fractions, and total EQD2 dose of 85 Gy to the CTVHR.
8.3.4 PTV for Brachytherapy If the CTVHR is treated by increasing the TRAK, than
this also leads to an increase in the dose in the lymph
In photon EBRT, the common approach is to pre-
nodes. The current recommendation is to report the
scribe the absorbed dose to the PTV with the as-
near-minimum dose, D98 %, for pathological lymph
sumption that the margins included in the PTV will
nodes even if the relevance of such reporting has not
result in the CTV receiving the prescribed absorbed
been validated. The median dose, D50 %, can be used
dose. In the case of homogeneous EBRT absorbed-
for research purposes.
dose distributions, the absorbed dose in the CTV will
For radiographic approximation, the concepts of
be similar to the absorbed dose in the PTV if CTV
the lymphatic trapezoid and pelvic wall points can
movements are within the PTV. However, in brachy-
be used as described in Section 10.1.5.
therapy, the situation is different due to the very
heterogeneous absorbed-dose distribution. If a PTV
margin is used around a CTV in intracavitary brachy- 8.4 OAR: Dose-Point and Dose – Volume
therapy, the absorbed dose would be systematically Parameters
lower than the CTV absorbed dose because the PTV
In the past, OAR dose constraints have often been
represents a larger volume, part of which is more
based on relative fractions of a prescribed absorbed
distant from the sources (Tanderup et al., 2010c).
dose [e.g., two-third of the prescribed absorbed dose
Also, uncertainties are different in intracavitary
at Point A allowed as maximum absorbed dose in the
brachytherapy (see Sections 5.4.6 and 5.5). Currently,
rectum (Stitt et al., 1992)], or 150 % to the lateral
there appear no compelling reasons to introduce PTV
vaginal surface of the applicator (Nag et al., 2002). As
dose reporting in routine brachytherapy practice.
noted by the authors of these reports, such relative
On the other hand, a pre-implantation PTV
absorbed-dose constraints cannot be used universally,
concept could be used during implantation to ensure
as changing the total target absorbed dose or chan-
that the applicator geometry results in a dose distri-
ging the fractionation schedule directly influences
bution covering the entire brachytherapy CTV with
absorbed-dose constraints for OARs. To reach the
the appropriate absorbed dose (see Section 5.5.6). A
most valid, reliable, and reproducible OAR dose as-
PTV in the cranio-caudal direction could also be used
sessment, dose-point, and dose–volume reporting of
for prescription to avoid a too-tight coverage at the
dose values to absolute volumes is strongly suggested
upper CTVHR, which might result in a geographical
in this report.
miss due to applicator movements between imaging
Analysis of the 3D dose distribution in an OAR
and during absorbed-dose delivery (see Figure 5.17).
has been based on two approaches: using a relative
Further research might provide additional support to
DVH in which the entire organ is contoured and the
use the PTV concept for dedicated treatment situa-
doses relate to the fraction of the contoured volume,
tions. However, for reporting, the CTV and not the
and an absolute DVH in which the doses relate to
PTV is the primary target volume in intracavitary
absolute volumes. Local pathologic-tissue altera-
brachytherapy because it represents a better esti-
tions in gynecologic brachytherapy, such as circum-
mate of the dose delivered.
scribed inflammation and fibrosis, telangiectasia,
ulceration, necrosis, or fistula, occur mainly in those
8.3.5 Lymph Nodes (D98 %)
volumes of hollow organs adjacent to the applicator
Lymph nodes can or cannot receive significant and exposed to high EQD2 (. from 70 Gy to 80 Gy)
absorbed doses in brachytherapy, and that absorbed to small volumes. Organ complications such as stric-
dose can be of particular interest for analysis of recur- ture, stenosis, and functional impairments occur
rences. There is a significant brachytherapy absorbed- mainly after irradiation of large organ volumes—
dose gradient along the lymph-node chains, and predominantly those including the whole circumfer-
therefore, the brachytherapy absorbed dose is vari- ence of hollow organs—with intermediate-to-high
able within each lymph-node region (see also Section EQD2 (from 40 Gy to 65 Gy, or more) (see Sections
10.1.5). It has been shown that the average absorbed 6.2 and 6.3).

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 Dose and Volume Parameters

2008; Jürgenliemk-Schulz et al., 2009; Kirisits et al.,

2005; 2006a; Levitchi et al., 2012; Lindegaard et al.,
2008; Mahantshetty et al., 2011b; Pötter et al., 2011).
However, due to the dose gradients throughout these
organs and the complex pattern of overall acute and
long-term morbidity, larger volumes are also of inter-
est for a comprehensive assessment and reporting of
morbidity. Therefore, in the following sections, both
small and large volumes are discussed for the various
OARs treated at high, intermediate, and low dose
levels, and recommendations for dose reporting are
given as based on current clinical evidence.

8.4.1. Bladder, Rectum, Sigmoid, and Bowel:

High-Dose Regions, Points, and Small
Volumes (D0:1cm3 , D2cm3 )
Typical brachytherapy-related adverse effects are
bleeding, local fibrosis, ulceration, necrosis, and
fistula, and—to some degree—urgency, frequency,
Figure 8.5. Sagittal view showing the volumes related to D0:1cm3 , and incontinence. The biological targets are small
D2cm3 , and a DV with V . 5 cm3. Note that if the dose to large
normal-tissue sub-volumes located mainly in the
volumes should be evaluated, delineation of an organ wall is
needed, while small volumes will be located mainly within the mucosa and sub-mucosa of the organ walls, and in
wall, even with whole-organ contouring. The location of the the neural plexus and muscles that regulate specific
bladder and recto-vaginal reference points are also shown. For functions of the bladder, rectum, and anus (see
the vagina, heavily irradiated volumes of approximately 2 cm3 Section 6.2).
and smaller are located adjacent to the lateral parts of the
Due to absorbed-dose heterogeneity within the
applicator not visible in this cross-sectional view (see Figures 8.12
and 10.1). organ walls, it is recommended to report at least two
dose–volume values in the high-dose region. The dose
values D0:1cm3 and D2cm3 represent, respectively, the
Bladder and rectal points delineated on radiographs minimum doses to the 0.1 cm3 and 2 cm3 volumes of
(see Section 10.3) have been widely used (ICRU, the OAR that receive the maximum dose. These OAR
1985). However, the large absorbed-dose inhomogen- parameters were recommended by the GEC ESTRO
eity in these adjacent organs results in poor character- GYN group in 2006 and seem to be useful in clinical
ization of the OAR dose when using point reporting practice, with first reports showing their validity for
only. Parts of the bladder, rectum, bowel, and vagina predicting morbidity (Georg et al., 2009; 2012;
walls are irradiated with doses close to or higher Jürgenliemk-Schulz et al., 2010; Koom et al., 2007;
than the minimum target doses. Wall segments, such Lang et al., 2006). An intermediate value for D1cm3 ,
as the posterior recto-sigmoid walls, the superior- appeared to add no additional information, as it can
anterior bladder wall, and the inferior vagina, receive be interpolated from the two other values. No
much lower brachytherapy absorbed doses (such as maximum point-dose reporting is recommended, es-
10 % to 20 % of prescribed CTV absorbed-dose values) pecially because of the limitations of calculating a
that have to be added to the EBRT absorbed doses. In maximum absorbed dose by sampling algorithms, 3D
combined brachytherapy and EBRT, there is an enor- reconstruction of volumes in treatment–planning
mous variation in the dose distribution in the adjacent systems, and contouring uncertainties (Kirisits et al.,
OAR walls (see Figure 8.5). 2007). Similar to the situation for the target, only a
Specific OAR volumes for treatment planning and near maximum absorbed dose as represented by the
dose reporting were introduced in the second GEC D0:1cm3 can be based on a sufficient number of sam-
ESTRO recommendations (Pötter et al., 2006). pling points for reproducible calculation. The volumes
Addressing mainly brachytherapy-related morbidity, for the D0:1cm3 and D2cm3 do not have a compact spher-
the analysis of doses in small volumes (0.1 cm3, 1 cm3, ical shape. Rather, they have sizeable extensions of
and 2 cm3) adjacent to the applicator, which receive more than 10 mm and 30 mm in the width and height
high doses, was recommended and has become wide- in the organ wall, respectively. As illustrated in
spread practice in centers using image-guided brachy- Figures 8.5 and 8.6, it is evident that D0:1cm3 and
therapy (Chargari et al., 2009; De Brabandere et al., D2cm3 do not represent point doses.

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 PRESCRIBING, RECORDING, AND REPORTING BRACHYTHERAPY FOR CANCER OF THE CERVIX

Figure 8.6. Three-dimensional reconstructed images showing contiguous 2 cm3 volumes in blue for the bladder and rectum, while it is
distributed in two parts for the sigmoid. The red-colored region receives at least the dose D0:1cm3 .

Figure 8.7. Cumulative DVHs of the bladder, rectum, and sigmoid, based on organ contouring indicating D0:1cm3 and D2cm3 . *Total EQD2
values for these OAR are given assuming four identical HDR fractions and an additional 25  1.8 Gy of EBRT, assuming a a/b value of
3 Gy.

The clinical effects in hollow OARs are related to contiguous. If the D2cm3 represents dose in two com-
irradiation of the organ walls only, and not of the pletely different parts of the sigmoid, it is believed to
entire organ that would include the lumen. In prin- have less clinical effect than one contiguous volume
ciple, OAR doses should therefore be evaluated in in the same organ region. In practice, the D2cm3
dose-wall histograms. However, as the volumes of appears as contiguous in the bladder (with limited
D0:1cm3 and D2cm3 are of limited thickness and bladder filling resulting in no extensive lateral
mainly located in the wall, it is possible to calculate recessus) and rectum, whereas in the sigmoid and
these parameters with sufficient accuracy based on bowel, it can often be distributed into several hot-
contours of the entire organs including the lumen spots as illustrated in Figure 8.6.
(Olszewska et al., 2001; Wachter-Gerstner et al., Another important aspect is the underestimation of
2003b). However, when evaluating dose in larger dose if the volume with the highest absorbed dose is
volumes, with parameters such as D5cm3 and D10cm3 , directly located at the recto-sigmoid junction. In the
dose-wall histograms are relevant, because when worst case, a contiguous 2 cm3 high-absorbed-dose
calculating DVHs for the entire organ, the absorbed volume could be distributed equally between both con-
doses in those volumes can include absorbed doses toured volumes, 1 cm3 per volume. However, as the
in the organ lumen. A different type of uncertainty DVH parameter is D2cm3 for a single organ contour, it
results when the reported volumes are not will report a lower value compared with the D2cm3 for

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 Dose and Volume Parameters

Figure 8.8. Rectum DVHs for two different schedules: (a in left panel) 45 Gy whole-pelvis EBRT plus 4 fractions of HDR brachytherapy
boost (total target dose 85 Gy EQD2), and (b in right panel) 45 Gy whole-pelvis EBRT plus 15 Gy EBRT tumor boost plus 2 fractions of
HDR brachytherapy boost (total target dose 85 Gy EQD2). The DVHs are given in terms of EQD2 for brachytherapy (blue), EBRT (green),
and total EBRT plus brachytherapy (red). The D2cm3 values are almost the same for the two scenarios, but the DVH shapes of total EQD2
are very different. In the scenario with a large brachytherapy contribution (a), the DVH in the high dose region is less steep than in the
case of a small brachytherapy contribution (b). This means that the D0:1cm3 value is higher in (a), whereas the intermediate doses are much
lower, with V60 Gy being 10 % in (a), and 49 % in (b).

the combined recto-sigmoid structure (see also assessment using D0:1cm3 and D2cm3 is relevant if
Section 6.3) (Lang et al., 2008). This demonstrates the organ structures are near the high-dose area of
importance of examining isodose distributions ana- brachytherapy for the duration of treatment (e.g., if
tomically, with which such a situation would be iden- they are fixed to the uterus). However, in the normal
tified and the volumes combined. clinical situation, as the bowel has to be assumed to
The use of both D0:1cm3 and D2cm3 allows character- be highly mobile, the spatial absorbed-dose distribu-
ization of only the high-dose part of the dose distribu- tion has to be studied and compared for each brachy-
tion in the organ at risk. The clinical effect and the therapy fraction. There is a high probability that
D2cm3 tolerance are likely dependent also on dose in these high-dose regions vary substantially between
adjacent intermediate- and low-dose regions visible different fractions. Adding the high-dose DVH para-
in the entire DVH, as shown in Figures 8.7 and 8.8. If meters without taking into account the varying
the contribution of EBRT is changed substantially spatial distribution of absorbed dose might substan-
(e.g., absorbed doses higher than from 45 Gy to tially overestimate the total EQD2 to the bowel and
50 Gy, as shown in Figure 8.8, or no EBRT contribu- might result in an unneeded compromise on tumor
tion), the DVH is directly influenced and changes its coverage. Further research on dose assessment and
shape considerably. Therefore, D2cm3 cannot be dose –effect relationships has to develop a more
expected to lead to identical effects across treatment valid dose-summation model, in which a differenti-
schedules with very different combinations of brachy- ation in effects among different anatomical parts of
therapy and EBRT. Similarly, a source position very the bowel might become possible.
close to the organ wall generates a different dose dis- As discussed in Section 8.2, a DVH for an entire
tribution. These changes are reflected in different organ provides no information about the spatial dis-
ratios D0:1cm3 /D2cm3 . Only by including reporting of tribution of dose within the organ. Individual doses
D0:1cm3 in such situations can very inhomogeneous to functional sub-units of organs must be assessed by
dose distributions with high values of D0:1cm3 be contouring sub-volumes and analyzing the corre-
detected and their potential biological effects taken sponding DVHs. A simple way for rough estimations
into account (see Figure 6.3). is the delineation of volumes at reproducible locations
Whereas the recommendation for reporting that show representative absorbed-dose values for a
D0:1cm3 and D2cm3 is straightforward for the rectum functional sub-unit. For example the bladder-neck
and bladder, the situation is different for the region and the trigone are of specific clinical rele-
sigmoid colon and the small bowel and other parts of vance, as the emptying function is located mainly in
the colon as the position of these organs is not static. this region, and it might be of interest for analysis to
For the sigmoid colon, the assumption of a static assess effects such as urinary urgency, increased fre-
absorbed-dose distribution across the organ wall for quency, and incontinence. During a transition period,
the summation of dose does not apply for the major- the use of point doses (e.g., the ICRU bladder point
ity of clinical scenarios (see Sections 6.4 and 8.5). related to the balloon fixed to the bladder neck) as a
For all other portions of the bowel, high-dose surrogate for the 3D dose distribution in sub-volumes

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and IMRT, only limited evidence has been provided

that would enable a clear understanding of the rela-
tion of this type of morbidity to irradiated (sub-)
volumes and thus facilitate recommendations for
treatment planning and reporting. It is evident that
doses from the EBRT component as illustrated in
Figures 8.8 and 8.9 to large organ volumes have to be
taken into account (see also clinical examples in the
Appendix). In principle, combined dose distributions
from both EBRT and brachytherapy should be consid-
Figure 8.9. External-beam radiation therapy DVHs for the ered. For practical reasons, outcomes related to larger
bladder, rectum, sigmoid, and abdominal cavity (bowel bag). It volumes or doses close to or lower than the EBRT pre-
can be seen from the DVHs that almost the entire rectum and scription might be assessed based on the EBRT plan
sigmoid are irradiated to the prescribed absorbed dose of 45 Gy only. The modeling of biological effects of irradiation
when using conventional 3D conformal techniques, whereas part
of the bladder may be outside the high-absorbed-dose region. The
for pelvic OARs becomes quite complex, and the use of
bowel (abdominal cavity) shows significant absorbed-dose a single dose to some part of an organ for characteriz-
variation over the organ. ing a biological effect seldom completely captures the
interrelationships of the effects of absorbed doses to
might remain important (ratio of DVH volumes sub-volumes of the organ. In the recent “Quantitative
versus point dose as described in Section 6.2). A Analysis of Normal Tissue Effects in the Clinic”
similar approach with point doses, which is currently (Bentzen et al., 2010; Kavanagh et al., 2010), the use
under investigation, might be followed for the ano- of a threshold model suggested that, at a certain
rectal region, with the related morbidity pattern of absorbed-dose level in a certain volume, a significant
anal urgency, stool frequency, and fecal incontinence. increase in adverse side effects is observed.
An anal reference point might be of interest (see For bowel morbidity, a V15 Gy of 120 cm3 is an esti-
Figure 6.4) as a surrogate for the 3D dose distribution mate for such a threshold if individual bowel loops are
in the anus or at the internal anal sphincter delineated. If the peritoneal cavity is contoured, a V45 Gy
of 195 cm3 was reported as threshold (Kavanagh
et al., 2010). Based on these findings, it is recom-
8.4.2 Bladder, Rectum, Sigmoid, and Bowel:
mended to report the DVH parameters for bowel
Intermediate- and Low-Dose and Non-
structures and state which anatomical parts (small-
Small Volumes
bowel loops, large-bowel structures, or entire perito-
Assessment of the bowel, sigmoid, and rectum mor- neal potential space of bowel) have been contoured.
bidity related to EBRT absorbed dose and volume has Specific parameters for intermediate absorbed-dose
long been a major concern with pelvic and abdominal assessment still need to be validated. VD parameters
radiotherapy. The volume of small and large bowel with D between 15 Gy and 50 Gy can be analyzed to
included in the radiation fields is a predictor for mor- define clinically relevant threshold levels. This VD
bidity (Haie et al., 1988; Letschert et al., 1990; 1994). can refer to absolute or fractional bowel volumes.
Bowel morbidity related to irradiation of large volumes Another strategy to analyze single values of the
is variable, with stenosis, stricture, and obstruction entire DVH in the intermediate dose region would
leading to major clinical symptoms that often require be a DV, i.e., to report the dose for a defined absolute
surgical intervention. Other symptoms include chronic or fractional bowel volume (e.g., for a volume V
(intermittent) diarrhea, chronic inflammation, cramp- between 10 cm3 and 200 cm3), or for a volume of 50
ing, gas production, and mal-absorption. % or 98 % or 2 % of the organ (compare Tables A1.2 –
Rectum morbidity is related mainly to transient A9.2 in the clinical examples in the Appendix).
bleeding, increased stool frequency and urgency, fecal For rectal morbidity (in particular bleeding), it has
incontinence, and also rectal stenosis. For bladder been recommended, mainly based on experience with
morbidity, the situation is complex. Global bladder- EBRT for prostate cancer (Fiorino et al., 2002;
related symptoms include reduced flow and capacity, Gulliford et al., 2010; Michalski et al., 2010; Nguyen
chronic inflammation, contracture, spasm, but also et al., 2010; Vargas et al., 2005) to refer to the amount
dysuria, increased frequency, urgency, and incontin- of rectal volume receiving 60 Gy (V60Gy). In cervical
ence. Urgency and incontinence are assumed to have cancer, most of the whole rectum and sigmoid has
also a major component with regard to the bladder been usually within the volume that is irradiated to
neck and the trigone. Other symptoms might be the prescribed EBRT absorbed dose (if a midline block
related to intermediate doses to volumes greater than is not applied), which means that most of the organ
2 cm3. However, even with 3D conformal radiotherapy receives 45 Gy or 50 Gy from the external-beam

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 Dose and Volume Parameters

portion of the treatment alone (Lim et al., 2009). This 8.4.3 Vagina High-, Intermediate-, and Low-
might be true also even for IMRT. Therefore, the V60 Dose Regions, Points, Small and Large
Gy is then very limited (see Figure 8.8 at the 10 % Volumes
volume level).
Radiotherapy-associated vaginal morbidity has been
For strategies with inhomogeneous EBRT ab-
investigated only to a limited extent. Recto-vaginal and
sorbed doses, such as with tumor boost, parametrial
vesico-vaginal fistula, extensive vaginal stenosis, and
boost, or simultaneous integrated lymph-node boost,
complete vaginal obliteration have represented the
the sigmoid and rectum can receive significant add-
major Grade 3 and Grade 4 events occurring in a
itional EBRT absorbed dose, increasing the amount
limited number of patients (Hintz et al., 1980).
of the organ irradiated to intermediate doses [see
Extensive stenosis and obliteration has been observed
Figure 8.8 and Fenkell et al. (2011)]. Irradiated
in patients mainly with extensive vaginal disease
volumes and intermediate absorbed-dose levels
treated with brachytherapy to a large part of the
should then be reported, such as VD starting from
vagina (Barillot et al., 2000). On the other hand, in the
45 Gy to 60 Gy and greater, or conversely to report
upper vagina near the vaginal sources, morbidity such
DV with V from 5 cm3 to 30 cm3 or as a fraction of
as adhesions, telangectasia, fragility (contact bleeding),
organ volume. These volumes are often spread over
mucosal pallor, fibrosis, shortening, and partial obliter-
the whole organ circumference and over a long part
ation (Grade1 and 2 toxicity) have been described in a
of the rectum or sigmoid.
large proportion of patients (see Figure 6.1)
For the bladder, the situation is even less clear, and
(Kirchheiner et al., 2012b; 2014).
the majority of studies have found no clear dose–
The vagina points located at the lateral vaginal-
volume relationship for intermediate doses of EBRT in
applicator surface and at 5 mm depth into the lateral
bladder and prostate cancer (Viswanathan et al., 2010).
walls of the vagina have traditionally been used for
The bladder shape and volume is highly variable, with
vaginal-dose reporting. Dose–effect relationships
changes in position, volume, and shape occurring
based on these points have not been well established,
during a course of radiotherapy and even during ad-
and the points have served mainly as tools for pre-
ministration of a single fraction. This causes uncertain-
scribing absorbed-dose constraints (Lee et al., 2012;
ties in the dose delivered, and the DVH from treatment
Viswanathan and Thomadsen, 2012; Viswanathan
planning cannot be assumed to represent accurately
et al., 2012b). There is evidence from evaluations of
the absorbed dose delivered by EBRT (Lim et al., 2009).
patient cohorts from the EMBRACE trial that the
However, in combinations of EBRT and brachytherapy
ICRU rectal point can be reliably used for a dose–re-
in cervical cancer, certain volume levels VD (D  40 Gy)
sponse analysis for vaginal shortening and therefore
or certain dose levels DV (V  10 cm3 or V as a fraction
can serve as surrogate point (recto-vaginal reference
of the organ volume) can be indicated based on the
point) to predict vaginal morbidity (Kirchheiner
treatment–planning CT and ignoring the daily
et al., 2016).
changes during fractionated EBRT. This would at least
Implementation and evaluation of valid and reliable
allow the determination of the amount of dose, mainly
dose–volume parameters for the high-absorbed-dose
from EBRT, given with some certainty to large bladder
region in the vagina (D0:1cm3 and D2cm3 ) are challenging
volumes in different treatment schedules with varying
due to the very high absorbed-dose gradients near the
contributions from EBRT and brachytherapy. In the
vaginal sources and the difficulties of precisely delin-
future, IGRT with repetitive imaging in combination
eating and reconstructing the thin organ walls on 3D
with protocols for bladder filling and CT protocols simu-
images with the applicator in place, using the currently
lating the potential bladder-volume changes (Ahmad
available treatment–planning systems (Berger et al.,
et al., 2012) will contribute to reduce uncertainties.
2007). No clear recommendations for dose–volume
As there is limited evidence for the validity of most
parameters relevant for morbidity in the vagina have
of these considerations with regard to intermediate
been developed so far. The dose–volume parameter
dose- and volume-assessment for combined EBRT
D2cm3 does not correlate with vaginal side effects in in-
and brachytherapy in cervical cancer, the proposed
dividual patients with cervical cancer treated within a
dose–volume parameters should be used with great
defined treatment protocol with very high brachyther-
caution in routine clinical practice. They are elabo-
apy doses (Fidarova et al., 2010). Dose–volume para-
rated here to suggest routes for future clinical re-
meters for larger vaginal volumes (e.g., 5 cm3 or
search. It is desirable at present to report a variety of
10 cm3) have not been investigated so far.
dose–volume parameters in the intermediate-dose
Despite limited evidence and progress in vaginal-
regions and in larger organ volumes and to correlate
morbidity analysis so far, a dose–volume or a dose–
them with specific morbidity endpoints in order to de-
surface concept for treatment planning and reporting
termine valid and predictive morbidity parameters
is, in principle, suggested here based on contouring
for treatment planning.

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lateral at the level of the vaginal sources, identical

to the approach recommended for dose reporting
when using radiographic localization (see Section
10.2). A high correlation between absorbed dose to
the surface and absorbed-dose points 5 mm deep
and absorbed-dose parameters for limited volumes
(e.g., D0:1cm3 and D2cm3 ), has been described based on
automatic contouring around the vaginal sources,
assuming a certain thickness of the vaginal wall
(Trnková et al., 2014). Therefore, it is likely that
these points will provide reasonable information for
the high-dose area around the vaginal sources.
Because of the inhomogeneous absorbed-dose dis-
tribution around the vaginal sources, the absorbed
dose to the lateral dose points is usually very differ-
ent from absorbed doses to points located in the an-
terior or posterior direction from the vaginal sources
(see Figure 8.10). For ring applicators, the absorbed
dose at anterior and posterior points will usually be
Figure 8.10. Plot of brachytherapy surface absorbed dose for the lower, due to the lateral loading. In ovoids, the
vagina using a ring applicator, frontal view. The absorbed-dose absorbed dose on the anterior or posterior vaginal
variation is high around the circumference at the level of the surface might be higher than in the lateral direction,
vaginal sources (ring: from 200 % to 100 % lateral in small areas, depending on the contribution and position of the
50 % to 70 % anterior and posterior in large areas) and along the
tandem and the distance from the active dwell posi-
axis in the cranio-caudal direction, with from 30 % to 80 % in the
mid-vagina and less than from 10 % to 30 % in the lower vagina tions to the anterior or posterior ovoid surface. Thus,
(compare Figure 8.11). points, while useful for dosimetric control, serve as
poor surrogates for the entire vaginal-surface
the whole vagina as a wall structure with a certain absorbed-dose distribution. This might explain the
thickness or as a surface structure. It can be assumed, lack of definitive relations between the absorbed
for obvious reasons, that late vaginal morbidity is dose to vaginal points and toxicity endpoints.
related to the different doses applied to different In conclusion, future research should aim to develop
vaginal parts, areas, and volumes. Figure 8.10 shows automatically generated contours around the vaginal
an example of an absorbed-dose plot for the vaginal applicators and along the whole vaginal surface, ex-
surface. As for other OAR, it is recommended that re- cluding the packing, for DSH/DVH evaluation. Such
search should aim at the implementation of a dose– methods would detect all locations of high and low
surface histogram (DSH) approach, with absolute dose throughout the vagina. The whole of this dosi-
values for planning and reporting vaginal dose based metric and volumetric information, together with
on an appropriate vaginal contouring, both for high topographic correlation, might be critical for finding
doses in small volumes and intermediate and lower parameters to predict vaginal morbidity.
doses in larger volumes related to anatomical vaginal Based on radiographic localization, the length of
regions. VD parameters with D from 5 Gy to 150 Gy the vagina irradiated to certain absorbed-dose levels
EQD2, DV parameters with V from 0.1 cm3 to 10 cm3, has been shown to be a surrogate for the vaginal
or certain fractions can serve to quantify the DVH. In volume and has been reported to predict major
cases in which DSHs are applied, DA with A indicating vaginal morbidity (Barillot et al., 2000). Therefore, it
representative areas can be reported. is recommended to analyze the dose profile from
Research and development have to provide the ap- EBRT and brachytherapy along the vaginal axis. An
propriate approaches to reduce relevant uncertain- example of such a dose profile is shown in Figure 8.11.
ties both in contouring and in dose and volume The length along the vaginal axis corresponding to
assessment. Such approaches might be in the form a certain dose can be measured from such dose pro-
of software-based methods to automatically delin- files. In order to further assess the intermediate- and
eate a surface around the vaginal packing, which low-dose regions in the vagina, anatomical reference
can be used to calculate DSHs and dose maps, and points along the vaginal axis can serve as surrogates
which would then include the entire dose informa- for the dose distribution in the vaginal wall: one at
tion for the vaginal wall. the mid-vagina [posterio-inferior border of the sym-
Following a long tradition, it is recommended to physis (PIBS) þ 2 cm], one at the transition from
report the absorbed dose at points at a 5 mm depth mid- to lower vagina (PIBS), and one at the lower

116
 Dose and Volume Parameters

Figure 8.11. Illustration of vaginal dose profiles for two different cases, showing the contribution of EBRT and brachytherapy dose to the
total EQD2. The x-axis starts at the upper vaginal surface and continues in the caudal direction along the central axis of the vagina.
Posterio-inferior border of the symphysis (PIBS) and PIBS + 2 cm points are shown. At the level of the ring-source path, a point (green) at
5 mm depth is indicated. The left case (PIBS) illustrates a representative situation with the lower field border of EBRT located close to PIBS.
The right case shows a situation with PIBS very close to the ring applicator. Definition of PIBSþ2 cm is not applicable anymore.
External-beam radiation therapy dose is substantially higher at PIBS as well as PIBS22 cm compared with the case at the left [from
Westerveld et al. (2013)].
region of the vagina (PIBS – 2 cm) (Westerveld et al., The situation is very different if the mid- and lower
2013). These points have been defined anatomically vagina form part of the CTVHR due to suspected re-
and reproducibly both for EBRT and for brachyther- sidual disease, and the usual vaginal applicators have
apy. Figure 8.12 shows a schematic diagram for this to be replaced with cylinders. In these cases, while the
approach. These points serve as anatomical reference target dose is included in CTVHR dose reporting, the
points both for brachytherapy and for EBRT and vaginal-surface dose along the applicator has to be
should be reported separately, and the doses added. given with much more detail in the spatial distribution,
For the mid-vaginal point that is at from 3 cm to 5 cm including high-dose regions along the circumference of
into the dose profile (see Figure 8.11), the dose from the cylinder surface (see Figure 8.12, cross sections).
EBRT is constant (prescribed dose), and variations
8.4.4 Other OAR
are determined by the brachytherapy dose. The dose
to the lower vaginal points (PIBS and PIBS22 cm) In addition to the OARs discussed above, there
depends mainly on the location of the lower field are other normal-tissue structures of interest, such
border of EBRT and inter-fraction variations, and is as ureter, anal canal, ovaries, urethra, large vessels,
constantly low and almost independent of brachy- large nerves, connective tissue, bone and bone marrow,
therapy if the vaginal length during brachytherapy is lymph vessels, and lymph nodes. Due to limitations in
5 cm–6 cm and is not treated explicitly by brachy- imaging and knowledge, identifying and contouring
therapy. However, the impact of brachytherapy dose and defining dose–volume constraints of these struc-
to the lower parts of the vagina can increase substan- tures is not straightforward. Consequently, further
tially if the vagina is short (see Figure 6.4), the imaging, contouring, treatment planning, and clinical
vaginal source is not placed at the vaginal apex, or if research is needed to link potential dose–volume para-
the vagina is treated due to involvement of disease. meters to morbidity outcome.

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 PRESCRIBING, RECORDING, AND REPORTING BRACHYTHERAPY FOR CANCER OF THE CERVIX

Figure 8.12. Sagittal views showing the vagina at the time of EBRT and at brachytherapy with an intracavitary applicator in place. At the
level of the vaginal source, dose points lateral to the rings or ovoids can be defined at 0 mm and 5 mm from the applicator surface. Three
additional points are defined along the central axis of the vagina in the cranio-caudal direction. The PIBS vaginal-dose point was defined
2 cm posterior from the posterior-inferior border of the pubic symphysis and for brachytherapy at the point of this line where it crosses the
applicator tandem. From there, two additional points 2 cm up and down along the vaginal axis are defined with PIBSþ2 representing the
mid of the vagina and PIBS22 representing the introitus level [from Westerveld et al. (2013)].

8.5 Specific Issues in Dose – Volume the full absorbed dose of external-beam therapy, if an
Reporting for the Combination of EBRT EBRT technique is applied with a homogeneous
and Brachytherapy absorbed-dose plateau (e.g., a four field box). Such an
assumption is not necessarily valid for the parts of
The simple addition of absorbed doses from EBRT
organ walls at a greater distance from the brachy-
and from brachytherapy is not meaningful because of
therapy applicator. Furthermore, the assumption
the different biological effectiveness associated with
might be less valid for techniques such as IMRT or
their delivery. Therefore, assessment of the total
intensity-modulated arc therapy (IMAT or VMAT)
equieffective dose from EBRT and brachytherapy
that can produce more-pronounced absorbed-dose
involves two steps: (1) the calculation of absorbed
gradients in those regions of OARs irradiated to high
dose to points, volumes, voxels, or regions from each
absorbed dose during brachytherapy. It follows that
fraction of EBRT and brachytherapy; (2) the applica-
care should be taken that hot spots from IMRT/IMAT
tion of the EQD2 or some other appropriate formal-
treatment plans should not coincide with the high-
ism on a point-by-point basis for dose summation (see
dose regions from brachytherapy. If boosts are given
Section 7.6). In principle, deformable registration
as part of the EBRT, a specific analysis of possible
could match each tissue voxel irradiated by each frac-
overlap of brachytherapy and EBRT dose distribu-
tion of external-beam radiation with the correspond-
tions must be performed, as additional dose to
ing voxel irradiated by each fraction of brachytherapy
CTVHR, CTVIR, or OAR structures can be significant
(see Section 9.4). However, currently no deformable-
(Van de Kamer et al., 2010). Evaluation of total dose
registration program is capable of tracking the loca-
is particularly challenging when a midline block or
tion and dose-exposure history of relevant biological
parametrial boost is used, because large gradients in
structures within the target volumes and OAR.
the absorbed dose from both the EBRT and brachy-
Currently, some simplifications and assumptions are
therapy are present in the same regions (Tamaki et
therefore suggested, which can be replaced by more
al., 2015). It has been shown that midline-blocked
appropriate approaches as this becomes technically
fields do not predictably protect OARs (D2cm3 ), nor do
feasible. These assumptions are suited for several
they predictably contribute absorbed dose to the
scenarios for typical treatment conditions. First, it
CTVHR or CTVIR (Fenkell et al., 2011).
can be assumed that the organ walls adjacent to the
A second assumption used for combining doses
applicator receiving a high brachytherapy absorbed
from EBRT and brachytherapy is related to accumula-
dose (such as D0:1cm3 and D2cm3 ) are irradiated with
tion of dose from succeeding brachytherapy fractions.

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 Dose and Volume Parameters

When adding doses for absolute OAR volumes (e.g., the recent GYN-GEC ESTRO Recommendations
D2cm3 and D0:1cm3 ), it is assumed that the location of (Haie-Meder et al., 2005). While prescription for the
the given high-absorbed-dose volumes is identical for treatment of a given patient, and the process of pre-
each brachytherapy fraction (Pötter et al., 2006). With scription itself, is left to the discretion of the individual
such an assumption, it is possible to calculate radiation oncologist, the use of the same concepts and
absorbed dose by crude addition of DVH parameters terms originally recommended for recording and
from each brachytherapy fraction. The assumption of reporting has been adapted and recommended for pre-
such a static situation predicts the highest dose pos- scription. Prescription in gynecologic brachytherapy
sible for the analyzed volume and the anatomical con- has typically been based on an absorbed dose to a point
figurations observed with imaging. It is linked to (mainly Point A), an absorbed dose to a defined isodose
uncertainties due to organ movement and deform- surface (ICRU, 1985), an absorbed dose to a set of dose/
ation and the applicator position (see Sections 9.2 volume parameters (Haie-Meder et al., 2005), or an
and 9.4), and uncertainties can vary for different absorbed dose defined in terms of TRAK (corresponding
organs according to their anatomical structure and fix- to the previously used product of radium mass and
ation, which also can vary with different treatment duration).
techniques. For example, for the anterior rectal and The definition of prescription as given in the GEC
posterior bladder wall 2 cm3 volumes, there is ESTRO recommendations did not clarify the prescrip-
some indication that the assumption of a static tion process, saying, “when prescribing to a target, the
anatomical dose distribution can be regarded as a valu- prescription dose is the planned dose to cover this
able approximation of the clinical situation in target as completely as possible” (Haie-Meder et al.,
the patient (Andersen et al., 2013). This is less clear for 2005). The term “as completely as possible” is then left
mobile organs such as the sigmoid. The static scenario to the discretion of the radiation oncologist responsible
is not a “worst case assumption,” as the organs might, for the treatment. Another common method to pre-
in addition, also move in relation to the applicator scribe the dose has been to relate the prescription to a
between imaging and absorbed-dose delivery, with the 100 % isodose that “covers” the target volume
possibility to deliver higher doses than reported. (Viswanathan et al., 2011b). Here, also, the term
With regard to the target, the relation between “covers” remains unclear. If the underlying under-
the intracavitary applicator and the outer part of standing is supposed to be full coverage, then the pre-
the target is often quite stable, and the lowest dose scription should be related to the minimum target
voxels are likely to be situated in the same region of absorbed dose, the D100 %. However, this is not the
the target for succeeding fractions. However, in widespread practice in clinical brachytherapy, and the
cases with an interstitial component, there can be D90 % was recommended in the GEC ESTRO recom-
significant differences in the location of the lowest mendations II (Pötter et al., 2006). In gynecologic
absorbed doses from implant-to-implant, which brachytherapy, the delivery of a dose to the entire
leads to an under-estimation of target near- target according to the initially planned dose is not
minimum dose parameters D98 % and D90 %. In con- always possible due to size and configuration of the
trast to the situation for the OAR, this means that target volume or OAR in relation to the applicator.
for the target D98 % and D90 %, a crude addition of Optimization includes the individual shaping of the
DVH parameters will result in a “worst-case as- absorbed-dose distribution in order to reach a com-
sumption” that assumes that the low-dose region is promise among the dose constraints for the target and
located in the same position for every fraction. the OARs (see Figure 10.2) (Tanderup et al., 2010a).
In clinical practice, it is of particular importance, Another scenario arises when the therapeutic window
to check the individual case as comprehensively as is sufficiently large: the target receives significantly
possible in case dose – volume outcomes exceed more dose than defined in the initial planning aim,
dose – volume constraints. Static scenarios might not while the OARs are within the specified dose con-
be applicable for all cases. straints. In both scenarios, the target dose of the
approved treatment plan will be different from the
initial planning aim (see Figure 10.2.)
8.6 From Planning Aims to Prescription In EBRT, a balance is struck between target- and
OAR-absorbed-dose constraints during the treatment–
8.6.1 Traditional Terms for Dose Prescription
planning process. The balance can be identical to or
Concepts and terms for a common language in different from the initial planning aim. ICRU Report
image-guided adaptive brachytherapy have been estab- 83 defined the process from the initial planning aim
lished for recording and reporting dose–volume para- to the prescription in a reproducible way with clearly
meters for the GTV and the CTV following the ICRU defined terms. The concepts and terms for gynecolo-
tradition (ICRU, 1993b; 1999; 2007; 2010) and that of gic brachytherapy will follow the same framework.

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8.6.2 Concepts and Terms: From Planning planning aim. In cervical brachytherapy, the differences
Aim to Dose Prescription between planning-aim dose and prescribed dose are es-
pecially pronounced if the planning aims for small
Following ICRU Reports 78 and 83, the goal for treat-
tumors are reached without the need to optimize for the
ment planning is the “planning-aim dose,” which is
OARs, resulting in very high prescription-dose levels.
determined before the treatment–planning process
(ICRU, 2007; 2010). The “prescribed dose” is the achiev-
8.7 Isodose Surface Volume
able dose chosen for treatment to a specific volume of
the target and approved by the radiation oncologist at The volume encompassed by an isodose surface is
the end of the treatment–planning process. The pre- called the isodose surface volume. The dose value for
scribed dose may or may not be equal to the this volume can be chosen to be clinically relevant for
planning-aim dose. In the clinical series reported so far, tumor control or development of complications.
there is a significant difference between planning-aim Isodose surface volumes can be used for comparison
dose and prescription dose (Chargari et al., 2009; De among institutions, or they can be used within a
Brabandere et al., 2008; Jürgenliemk-Schulz et al., single institution to follow the transition from institu-
2009; Kirisits et al., 2005; 2006; Levitchi et al., 2012; tional standard loading to optimized treatment plans.
Lindegaard et al., 2008; Mahantshetty et al., 2011; The term, “isodose surface volume,” replaces the
Pötter et al., 2011). The new concepts for the terms terms “volume of prescribed dose” or “100 % dose.” As
“planning aim” and “dose prescription” take into account previously described, individualized dose prescription
the stepwise brachytherapy planning procedure, start- can be performed, and therefore the reporting of
ing with initial aims for treatment planning and ending volumes related to a fraction of a prescribed absorbed-
with an approved treatment plan and a prescribed dose. dose value as V100 %, V200 %, etc. becomes useless
The planning aim defines a set of intended dosimetric without stating the normalization value if the pre-
parameters and constraints for the target and the OARs scribed value is changing for each individual treat-
that are used to develop the treatment plan. The dose– ment plan. Therefore, it can be helpful to keep certain
volume constraints for the OARs and target are defined absolute dose levels fixed for reporting and for follow-
initially according to clinical evidence, to institutional ing the planning procedure from the initial standard
rules or according to patient-specific considerations. plan to the optimized plan. An isodose surface volume
Through individual treatment planning, a finally should be linked to a dose that is judged as represen-
accepted set of treatment parameters is achieved, balan- tative for a certain clinical effect. Typical dose values
cing dose–volume constraints for the OARs and for the are the planning-aim dose per fraction for HDR or
target, for example, a D90 % for the CTVHR of 7.4 Gy, a PDR treatments (e.g., 7 Gy in an HDR treatment of
D2cm3 for the rectum, sigmoid, and bladder of 3.5 Gy, 4  7 Gy), or the total absorbed dose given in LDR or
3.2 Gy, 5.5 Gy, respectively, for one single fraction within PDR treatments of 60 Gy or 15 Gy.
an HDR schedule of four fractions. The set of these para- For comparison of irradiated volumes among dif-
meters derived from the planned treatment becomes the ferent institutions, it is of little relevance to report
prescription, which is approved by the responsible radi- the volumes irradiated with the planning-aim dose
ation oncologist. For each brachytherapy fraction, a set because such volumes would be related to the individ-
of prescription parameters will be generated which ual institutional dose levels. It is necessary to choose
might or might not vary. common dose levels according to clinically relevant
Within this new definition of prescription, it is neither EQD2 values, such as 60 Gy, 75 Gy, or 85 Gy (Pötter
reasonable nor necessary, and probably not possible, for et al., 2002b). In order to evaluate such isodose
adaptive image-guided brachytherapy in cervical cancer volumes, the fractional brachytherapy absorbed dose
to use the same prescribed dose for all patients in a spe- must be calculated that corresponds to the total dose
cific patient cohort. Reporting prescribed doses for a of interest. As an example, fractional absorbed doses
patient group by one single value is then not appropri- of 7.1 Gy, 5.8 Gy, and 3.5 Gy correspond to an EQD2
ate; the report must include the mean or median value, (a/b ¼ 10 Gy) of 85 Gy, 75 Gy, and 60 Gy, respectively,
standard deviation (SD), and range. The prescribed dose assuming a schedule of 4 similar fractions of HDR
can also be reported in terms of the total dose from brachytherapy with 45 Gy in 25 fractions of EBRT.
EBRT and brachytherapy using EQD2 as, for example, The isodose surface volume can be reported as a
a D90 % of 92 Gy + 13 Gy (1 SD), while the initial plan- volume as well as by indicating the maximum dimen-
ning aim was to deliver at least 84 Gy (Pötter et al., sions of height, width, and thickness (ICRU 1985). It can
2011). In EBRT, the situation is somewhat different be useful to compare the volume treated independent
because the prescription absorbed dose is usually very from the individual planning aims as a constancy check.
similar to the planning aim and becomes identical if the The volume encompassed by the planning aim
absorbed dose plan is normalized according to the isodose surface is of special interest. The location,

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dimension, and shape of this volume when compared 8.8 Recommendations for Reporting
with the target are of interest because this informa-
tion contributes to the assessment of conformality.
In order to illustrate the use of the isodose surface Level 1: Minimum standard for reporting
volume concept, an example is given in Figure 8.13
for an HDR schedule with 4 fractions of brachyther- Dose reporting
apy and a planning-aim absorbed dose of 7 Gy for † TRAK
the CTVHR. A similar example is the use of the † Point A dose
† Recto-vaginal reference point dose
60 Gy volume for cases in which the planning aim
† D0:1cm3 , D2cm3 for the bladder, rectum
and dose prescription is linked to the CTVIR.
(Compare tables for the clinical examples in the
Appendix A.1.4-A.9.4.)
Level 2: Advanced standard for reporting
All that is reported in level 1 plus

Dose reporting for defined volumes

† D98 %, D90 %, D50 % for the CTVHR
† (D98 %, D90 % for the CTVIR if used for prescription)
† D98 % for GTVres
† D98 % for pathological lymph nodes
Dose reporting OARs
† Bladder reference-point dose
† D0:1cm3 , D2cm3 for the sigmoid
† Dcm3 for the bowel
† Intermediate- and low-dose parameters for the bladder,
rectum, sigmoid, and bowel (e.g., V15 Gy, V25 Gy, V35 Gy, V45 Gy, or
D98 %, D50 %, D2 %)
† Vaginal point doses at level of sources (lateral at 5 mm)a
† Lower and mid-vagina doses (PIBS, PIBS + 2 cm)a

a
Surrogate points for volumetric vaginal-dose assessment.

Level 3: Research-oriented reporting

All that is reported in Level 1 and 2 plus

Figure 8.13. Schematic drawing illustrating the absorbed-dose Absorbed-dose reporting for the tumor:
distribution in relation to the CTVHR. The dotted lines illustrate † D98 %, D90 % for the CTVIR even if not used for prescription
the situation for a standard loading intracavitary-only plan † D90 % for the GTVres
with normalization to Point A, while the solid lines are for † DVH parameters for the PTV
an optimized combined intracavitary/interstitial plan. During † D50 % for pathological lymph nodes
the planning process, a planning-aim absorbed dose of 7 Gy is † DVH parameters for non-involved nodes (ext/int iliac, common
normalized to 100 %, which is also the dose to Point A in the iliac)
standard plan. For this non-optimized plan, the D90 % reached OAR volumes and points
only 6.1 Gy, while after optimization, the D90 % was increased to † Additional bladder and rectum reference points
8 Gy. The finally prescribed dose is related to the D90 %, which is † OAR sub-volumes (e.g., trigonum or bladder neck, sphincter
indicated in blue. It is important to note that, despite a large muscles)
increase for the D90 %, the overall isodose volumes that are achieved † Vagina (upper, middle, lower)
after optimization remain similar or can become even smaller than † Anal canal (sphincter)
the volumes using standard loading. The geometrical configuration † Vulva (labia, clitoris)
changes significantly with optimization, which is seen in this case as † Other volumes/sub-volumes of interest (e.g., ureter)
a larger right-lateral width at the level of the residual parametrial Dose–volume reporting for OARs
tumor (Point A) and a reduced length at the upper tandem according † Dose–volume and DSH parameters for additional OARs and
to the limited residual-tumor spread into the uterine corpus. On the sub-volumes
other hand, the length and width was changed very little at the † Vaginal dose profiles, dose–volume, and DSHs
vaginal level, as no major optimization was performed in this region. † Length of treated vagina
The thickness might be less affected by these geometrical changes. Isodose surface volumes
The 7 Gy isodose surface volume was, by chance, in the standard and † 85 Gy EQD2 volume
optimized case identical with 112 cm3, because the optimization † 60 Gy EQD2 volume
decreased the volume in the uterine direction and increased it in the
right-lateral direction.

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8.9 Summary The vagina, both as a potential target and

an OAR, needs appropriate metrics for a comprehen-
This section has given the relevant background
sive volumetric dose assessment covering high-,
and recommendations to prescribe, record, and
intermediate-, and low-dose regions. Due to inher-
report dose distributions for cervical cancer treat-
ent problems in dosimetric assessment of thin-wall
ments. The complete information requires reporting
structures in the vagina, alternative strategies are
the detailed spatial distribution of dose in relation to
recommended, including a specific set of dose points.
target structures and OAR, sometimes with specific
Other OARs such as urethra, ano-rectum, and
parameters for their sub-structures. With volumet-
ureter might also be considered.
ric imaging, defined volumes can be contoured, and
In general, DVHs for gross OAR contours lack in-
consequently DVH parameters can be utilized to
formation on the spatial dose distribution within
quantify dose distributions resulting from treatment
organ sub-structures, which are in turn respon-
planning. Although parameters such as D90 %,,
sible for various morbidity endpoints. This fact
D2cm3 , and others are linked to fixed dose or volume
might substantially limit the current understand-
values on the DVH, they lose spatial information.
ing of dose/volume-effect relations. The need for
For that reason, reference points remain important.
future research on sub-volume analysis is empha-
For both the CTVHR and the CTVIR, the D90 % and
sized for specific morbidity endpoints together
the near minimum dose, D98 %, are recommended,
with reference points or volumes for these struc-
as they have been demonstrated to be representative
tures (bladder/vagina/anus).
clinically relevant-dose levels. In addition, the
Absorbed-dose reporting to Point A and TRAK
median dose, D50 %,, is also suggested . Together
remains a minimum standard requirement for any
with D98 % and D90 %, D50 % characterizes the large
brachytherapy treatment, although volumetric assess-
dose inhomogeneity within the CTV and, in particu-
ment is recognized as the method of choice. Point A and
lar, the dose to the high-dose volume, which is
TRAK reporting is reproducible and straightforward;
typical in intracavitary treatments. As the use of a
moreover it enables comparisons among present, past,
PTV is not straightforward for intracavitary brachy-
and future clinical practice and among different levels
therapy, reporting of DVH parameters for the PTV is
of complexity for dose reporting.
currently limited to research. The D98 % is recom-
The use of “isodose surface volumes” is introduced
mended for reporting absorbed dose to the GTVres
to compare treatment strategies between Centers
and to pathological lymph nodes.
and during the planning process within Centers.
For OARs, such as the bladder and rectum, the
These are volumes contained within an encompass-
DVH parameters D2cm3 and D0:1cm3 are recommended
ing isodose surface. The term “reference volume,” the
to describe the high-dose regions within these OARs.
volume receiving 60 Gy, as introduced for target-
Furthermore, these parameters are regarded as being
related reporting in ICRU Report 38 is no longer
sufficient to assess brachytherapy-related morbidity if
recommended in this report.
the relative contributions of EBRT and brachytherapy
The whole process of treatment planning, dose pre-
to the overall treatment dose remain constant.
scription, and reporting as traditionally performed for
Additional DVH parameters for the intermediate-
cervical cancer brachytherapy is redefined and ampli-
and low- dose regions are important to characterize
fied by introducing “planning aims” and “final pre-
morbidity (e.g., stenosis, stricture) related to larger
scription.” The planning aims are dose and volume
irradiated volumes of the OAR. These parameters
values defined prior to treatment planning and might
can be essential in situations in which larger contri-
ultimately not be achievable. The prescription defines
butions to the total absorbed dose are delivered with
the finally accepted set of values, after treatment-
EBRT. In the case of brachytherapy-only treatments,
plan acceptance. It can differ from the planning aims
the high-dose parameters D2cm3 and D0:1cm3 are es-
as a result of compromises among target and OAR
sential but not sufficient for comparison to treat-
doses.
ments with a large component of EBRT (e.g., 45 Gy).

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