Medical Dosimetry 46 (2021) 269–273

Medical Dosimetry
journal homepage: www.meddos.org

A predictive model for determining rectum and bladder dose

constraints in prostate volumetric modulated arc therapy
Menglei Chao, MRT ∗,∗∗, Natalie Coburn, BAppSc ∗, Eireann Cosgriff, DPhil ∗,1, Chris Brown, MBiostat ‡,
Kevin Van Tilburg, DipAppSc ∗, Amy Hayden, MBBS, FRANZCR ∗,†
∗
Nepean Cancer Care Centre, Nepean Hospital, Kingswood, New South Wales, 2747, Australia
†
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia
‡
NHMRC Clinical Trials Centre, The University of Sydney, Campbelltown, New South Wales, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Generic dose-volume constraints of the rectum/bladder (R/B) are used in inverse planning to reduce doses
Received 17 August 2020 to these organs for patients undergoing prostate radiotherapy. A retrospective study was undertaken to
Revised 22 November 2020
assess correlations between the overlap of the R/B with the planning target volume (PTV) and the dose
Accepted 5 February 2021
received during planning to organs at risk (OARs). Data for 105 prostate cancer patients who had vol-
umetric modulated arc therapy (VMAT) to the intact prostate and proximal seminal vesicles at Nepean
Keywords: Cancer Care Centre from 2011 to 2015 were analyzed. R/B volume, R/B-PTV overlap volume, and R/B-PTV
Volumetric modulated arc therapy overlap percent metrics were collected with VMAT planning objectives. Characteristics were evaluated
Inverse radiation treatment planning for correlation with different planning outcomes. The percentage overlap between the R/B and PTV were
Prostate cancer
highly correlated to the doses to the relevant OAR, with a coefficient of determination (R2 ) of 0.63 for the
Organs at risk dose sparing
Predictive model rectum volume percentage receiving more than 75 Gy (RV75Gy ) and R2 of 0.91 for the bladder volume per-
centage receiving more than 70 Gy (BV70Gy ). We identified a cut-off value of 10.14% (sensitivity 84.62%,
specificity 80.43%) as predictive of RV75Gy < 10% and a cut-off of 7.95% (sensitivity 97.62%, specificity
92.06%) as predictive of BV70Gy < 15%. A 95% prediction interval assisted in identifying individualized R/B
planning goals. The R/B-PTV percentage overlap has a high reliability in estimating sparing of the R/B.
This prediction model can be used to improve planning efficiency and create customised automated OAR
planning goals in prostate VMAT plans. By doing this, the radiation doses received by these OARs can be
minimized.
Crown Copyright © 2021 Published by Elsevier Inc. on behalf of American Association of Medical
Dosimetrists. All rights reserved.

Introduction there is considerable overlap of the rectum/bladder (R/B) with the

Volumetric modulated arc therapy (VMAT) is a widely used
technique for treating prostate cancer patients.1 Compared to other
radiation treatment modalities such as 3D conformal radiation
therapy, VMAT, as a sophisticated version of intensity modulated
radiation therapy (IMRT), shows its superiority in terms of achiev-
ing organ-at-risk (OAR) sparing while maintaining sufficient plan-
ning target volume (PTV) coverage and reduced beam-on time.1 , 2
However, VMAT planning can become more time consuming when
∗∗
Reprint requests to Menglei Chao, MRT, Nepean Cancer Care Centre, Nepean
Hospital, Cnr Great Western Highway and Somerset Street, Kingswood, New South
Wales, 2747, Australia.
E-mail address: menglei.chao@health.nsw.gov.au (M. Chao).
1
Present address: Crown Princess Mary Cancer Centre, Westmead Hospital,
Westmead, New South Wales, Australia.
PTV. Overlap can occur because of poor bowel and bladder prepa-
ration, variations in the PTV expansion, or the anatomical location
of R/B with respect to the PTV.3 If difficulties in achieving R/B dose
constraints can be predicted effectively, radiation oncologists can
be consulted at an earlier stage of planning to determine if PTV
coverage can be compromised or rescan the patient with better
bowel/bladder preparation as soon as possible, and clinical inter-
ventions such as space OAR insertion can be applied if needed. If
clinical intervention is not applicable, a set of more realistic plan-
ning constraints are needed in the patients’ best interest. This will
improve planning efficiency by reducing time spent on difficult
plans by planners with variable planning experience. There is also
a possibility to tighten R/B planning goals for patients with rela-
tively small R/B overlaps who can easily achieve current standard
OAR constraints.

https://doi.org/10.1016/j.meddos.2021.02.005
0958-3947/Crown Copyright © 2021 Published by Elsevier Inc. on behalf of American Association of Medical Dosimetrists. All rights reserved.
270 M. Chao, N. Coburn and E. Cosgriff et al. / Medical Dosimetry 46 (2021) 269–273

Table 1 Table 2
Prescription goals and OAR constraints of the VMAT prostate plans Pearson correlation between the rectum overlap volume (ROV), rectum overlap per-
centage (ROP), and plan parameters
Dose (Gy) Volume Abbreviation
ROV ROP
CTV 78 >99% (accept CTV D99%
>98%) p value R2 p value R2
PTV 74.10 >99% (accept PTV D99% RV75Gy <0.01 0.42 <0.01 0.63
>98%) RV70Gy <0.01 0.390 <0.01 0.64
Max dose 83.46 <1 cc RV60Gy <0.01 0.30 <0.01 0.56
RV40Gy 0.01 0.07 <0.01 0.16
Rectum 78 <2 cc RVLG78Gy
RVLG78Gy <0.01 0.18 <0.01 0.12
75 <10% RV75Gy
LHOF V30Gy 0.08 0.03 0.39 0.01
(accept <15%)
RHOF V30Gy 0.15 0.02 0.28 0.01
70 <20% RV70Gy
Max dose 0.54 0.0037 0.04 0.04
60 <35% RV60Gy
CTV D99% 0.01 0.06 <0.01 0.08
40 <60% RV40Gy
PTV D99% 0.01 0.06 <0.01 0.16
Bladder 78 <2 cc BVLG78Gy
70 <20% BV70Gy
50 <50% BV50Gy
Head of femur 50 <5% HOF V50Gy were established based on knowledge and understanding of the Cancer Institute
30 <60% HOF V30Gy NSW eviQ external beam radiotherapy guidelines for prostate cancer.10 , 11 All pa-
tients were treated with either one or two full arcs on an Elekta Synergy S linear
accelerator (Elekta, Crawley, UK). The VMAT prostate plans in this study were de-
livered clinically, and the prescription goals for the CTV and PTV in all plans were
Mathematical models have been established to predict dose– met.
volume histograms (DVHs) based on individual patient anatomy
prior to optimization of radiation therapy treatment plans for head Data collection
and neck cancer and prostate cancer patients.4 , 5 As the PTV gets
the prescription dose in VMAT prostate plans, the portion of R/B The percentage volumes of the CT V or PT V receiving 78 Gy or
overlapping with the PTV receives a comparatively higher dose 74.1 Gy were recorded (denoted V78Gy and V74.1Gy , respectively).
than the area outside the PTV. Some studies have demonstrated The maximum dose was defined as the highest dose in each plan.
that the magnitude of R/B–PTV overlapping volume has a strong The volume of tissue receiving more than 83.46 Gy (107% of the
correlation with doses to the relevant OAR in both IMRT and VMAT prescription dose) was also computed. The volume of the R/B
plans.6 , 7 (RV/BV) as well as the overlapping volume of R/B with the PTV
The goal of this study was to identify the relationship between (ROV/BOV) was recorded. The percentage of R/B overlapping with
/BOV
R/B–PTV overlaps and the achieved R/B DVHs in prostate VMAT the PTV (ROP/BOP) was defined as ROV RV/BV . DVHs of each OAR
plans and establish an efficient and reliable model to predict doses were evaluated, as per department guidelines (Table 1).
to the R/B for future cases. It is expected that patients with un-
achievable R/B goals can be identified prior to plan optimization Statistical methods
and that physician intervention could then occur earlier in the
Pearson correlations were computed to assess the relationships between the
planning process. For plans that exceed the OAR dose limits, this dose volume constraints of each OAR and the BOV/ROV and BOP/ROP. The correla-
model can be used to guide the planner in achieving realistic OAR tion was summarised as the coefficient of determination (R2 ). A p-value <0.01 (for
sparing and eventually improve plan quality. The same mathemat- the test against R2 = 0) was considered indicative of correlation. Predictive factors
ical method can be applied to patients with smaller R/B-PTV over- for the R/B constraints in the VMAT prostate plans were used to determine a pre-
dictive equation using linear regression analysis applied to the most correlated dose
laps in order to establish customized planning goals and achieve
volume parameters. Scatterplots were created to present the correlations between
lower radiation doses to these OARs. Customized planning goals the ROV/BOV and ROP/BOP with the dose volume outcomes. A 95% prediction inter-
can also be adapted within an automated planning programme to val was computed to assess the magnitude of variation. Receiver operating charac-
guide the planner to reach an optimal plan sooner.8 , 9 teristic (ROC) curves were computed to determine optimal cut-off values for future
clinical application. The analysis was performed using SAS (version 9.4).
Methods
Results
Patient selection and radiation technique
The rectum and bladder total volumes (RV/BV) varied among all recruited pa-
A total of 108 consecutive prostate cancer patients who received VMAT radio- tients as well as the R/B–PTV overlap volume and percentage. The RV ranged from
therapy at the Nepean Cancer Care Centre (NCCC) between Dec 2011 and May 2015 24.83 cm3 to 140.64 cm3 (median = 53.53 cm3 ), and the ROV ranged from 0.58 cm3
were enrolled in this retrospective study. All patients were diagnosed with low or to 16.12 cm3 (median = 4.51 cm3 ). The ROP values ranged from 1.13% to 19.19% (me-
intermediate risk prostate cancer with no metastatic lymph nodes. Three patients dian = 8.24%). The BV ranged from 47.93 cm3 to 849.67 cm3 (median = 247.05 cm3 ),
with hip prostheses were excluded from this database. This project has been ap- and the BOV ranged from 3.52 cm3 to 42.78 cm3 (median = 17.23 cm3 ). The BOP
proved by Nepean Blue Mountains Local Health District (NBMLHD) Human Research values ranged from 0.79% to 28.76% (median = 7.06%).
Ethics Committee. The Pearson correlation between the ROV/ROP and BOV/BOP with the plan pa-
All patients underwent a simulation CT using a GE Lightspeed RT (Boston, MA). rameters are shown in Tables 2 and 3. Both the ROV and ROP have significant as-
Patients were scanned supine with an empty bowel and a comfortably full blad- sociations with the rectum dose volume constraints (RV75Gy , RV70Gy , RV60Gy , and
der, as per the department’s prostate bladder/bowel preparation guideline. Any pa- RV40Gy ; p < 0.01). The ROP has a higher R2 value than that of the ROV. There are
tients with unsatisfactory bowel or bladder preparation required a rescan. The clin- also significant correlations between the BOV/BOP and bladder dose volume con-
ical target volume (CTV) included the intact prostate and proximal seminal vesicles straints (BV70Gy and BV50Gy ; p < 0.01), and the BOP has a higher R2 value than that
and was expanded to form the PTV by 7 mm in all directions except posteriorly, of the BOV. Among all the rectum constraints, RV75Gy and RV70Gy have the two high-
where a margin of 5 mm was applied. The rectum was outlined by the radiation est R2 values (R2 = 0.63 and R2 = 0.64 respectively, both p < 0.01) and BV70Gy has
oncologist from the level of ischial tuberosities to the rectosigmoid junction. The the highest R2 value within the bladder constraints (R2 = 0.91, p < 0.01). No signif-
bladder and head of femur contours were completed by the radiation therapist ac- icant correlation was observed in the rectum and bladder overlap and plan maxi-
cording to departmental policy. The Pinnacle3 treatment planning system (versions mum dose or head of femur constraints. Rectum and bladder overlap also have a
9.6, 9.8 and 9.10, Radiation Oncology Systems, Fitchburg, WI) was used to generate significant correlation with the PTV coverage (p < 0.01).
all the prostate VMAT plans in this study by using generic inverse planning objec- Predictive equations were generated using linear regression analysis. The
tives to satisfy the dose prescription and OAR constraints as per the departmental equation to predict RV75Gy using the ROP is y = 56.51x + 2.72 with a R² of
prostate planning objectives listed in Table 1. The standard prescription dose for 0.62 (y = RV75Gy , x = ROP). The equation to predict BV70Gy using the BOP is
VMAT prostate treatments at NCCC is 78 Gy in 39 fractions. The plan objectives y = 114.94x + 3.64 with a R² = 0.91 (y = BV70Gy , x = BOP). The R² values of these two
 M. Chao, N. Coburn and E. Cosgriff et al. / Medical Dosimetry 46 (2021) 269–273 271

Fig. 1. Rectum volume percentage receiving more than 75 Gy as a function of the (a) rectum overlap percentage and (b) rectum overlap volume. Bladder volume percentage
receiving more than 70 Gy as a function of the (c) bladder overlap percentage and (d) bladder overlap volume.

Table 3 der are the two main organs of concern. Some researchers have
Pearson correlation between the bladder overlap volume (BOV), bladder overlap
found that a 10% increase in bladder volume will reduce the blad-
percentage (BOP), and plan parameters
der mean dose by 5.6% and the presence of gas in the rectum may
BOV BOP alter its received dose.12 Overlap of these 2 organs and the PTV
p value R2 p value R2 have been noted in almost all prostate plans in our study due to
BV70Gy <0.01 0.16 <0.01 0.91
the anatomical location of these organs and the PTV. The size of
BV50Gy <0.01 0.14 <0.01 0.84 the overlapping area will have an impact on the quality of the
BVLG78Gy <0.01 0.17 <0.01 0.15 IMRT/VMAT prostate radiation treatment. When the PTV overlaps
LHOF V30Gy 0.04 0.04 0.26 0.01 too much with the bladder or rectum, it will be difficult or even
RHOF V30Gy 0.49 0.0047 0.17 0.02
impossible to meet their corresponding OAR dose volume con-
Max dose 0.02 0.05 0.01 0.06
CTV D99% 0.37 0.01 0.07 0.03 straints without compromising PTV coverage. The planning process
PTV D99% <0.01 0.19 <0.01 0.18 can be prolonged by attempting to satisfy planning goals which are
unachievable. Planners with various levels of planning experiences
equations indicate the reasonable predictive ability of the model. In Fig. 1, scatter might struggle to achieve a consistent optimal plan in the end. As
plots show comparisons between the ROV and ROP as well as the BOV and BOP. a consequence, patient treatment could be delayed and clinical re-
The ROP and BOP show a stronger linear correlation with the dose volume param- sources wasted. Therefore, it would be helpful in the early stages
eters than the ROV and BOV. From the ROC curves in Fig. 2, the ROP cut-off value of planning, if we could recognize plans that result in unachiev-
that could be used to predict RV75Gy < 10% is 10.14% (sensitivity 84.62%, specificity
able planning goals and implement effective interventions. In con-
80.43%). The BOP cut-off value to predict BV70Gy < 20% is 7.95% (sensitivity 97.62%,
specificity 92.06%). The 95% prediction intervals in Fig. 1 account for 95% of the trast, when the R/B overlap volumes are relatively small and their
variables of the RV75Gy and BV70Gy constraints in the recruited patients. The area OAR dose goals are easily achieved, planners may be satisfied with
between the 2 intervals indicates the predictive constraint values with the corre- their plan and stop the optimization. In this case, the treatment
sponding ROP or BOP values.
plan could be suboptimal according to the ALARA radiation safety
principle. Literature has shown correlations between the overlap-
Discussion
ping volume and radiation dose received by R/B and the possibility
of predicting OAR dose by using the degree of overlap in IMRT and
The development of advanced radiotherapy techniques such as
VMAT prostate radiotherapy plans.6 , 7 Our study has applied these
IMRT and VMAT aims to achieve better therapeutic dose escalation
previous theories to our centre’s practices and developed a suitable
and OAR sparing. In prostate radiotherapy, the rectum and blad-
predictive model.
272 M. Chao, N. Coburn and E. Cosgriff et al. / Medical Dosimetry 46 (2021) 269–273
Fig. 2. Receiver operating characteristic curves of the (a) rectum overlap percentage and (b) bladder overlap percentage.
In this study, we have shown that the ROV/BOV and ROP/BOP
are both highly correlated with the dose received by the R/B not
only in the high-dose region but also in the low-dose region of the
R/B DVH. We also found that the ROP/BOP has a much stronger
association than that of the ROV/BOV especially for high-dose R/B
goals (RV75Gy and RV70Gy or BV70Gy and BV50Gy ). This means that
the ROP/BOP has better predictive ability than the ROV/BOV for
VMAT prostate plans and could be used to acquire estimated R/B
doses accordingly by applying the linear equations presented here.
The R/B overlaps were also found to be adversely associated with
the 99% PTV coverage but to a lesser extent with the 99% CTV cov-
erage. This is because the CTVs in prostate VMAT plans do not
overlap with either the bladder or rectum. The plan maximum
dose and head of femur doses were not significantly affected by
the R/B overlaps from our study results. To determine an optimal
cut-off value of the ROP for predictive purposes, the current rec-
tum constraint of 75 Gy was reduced from 15% to 10% (all our re-
cruited plans met the RV75Gy < 15% constraint). RV75Gy can be con-
sidered as an ideal predictive variable given its high sensitivity and
specificity. Similarly, the BOP cut-off value with its high sensitivity
and specificity can be used as a predictive factor prior to the plan-
ning process. These cut-off values alert planners to VMAT prostate
plans that might have unachievable RV75Gy and BV70Gy goals. In ad-
dition to these cut-off values derived from the ROC curves, we can
also use the 95% prediction interval to predict the dose range for
an individual patient. Theoretically, the mass majority of the blad-
der/rectum dose (RV75 Gy/BV70 Gy dose) should fall in the dose
range between the 95% prediction interval based on the degree of
overlap. The planner should aim to achieve bladder/rectum doses
below those indicated by the central line in the scatter plot graphs.
Patients present with various degrees of PTV–OAR overlap, and the
estimated dose constraint range can be used as customized plan-
ning goals.
The outcome of our study is consistent with the findings of pre-
vious studies. Moore et al.13 developed a quality control tool by us-
ing the percentage OAR–PTV overlap in both prostate and head and
neck IMRT plans and successfully reduced mean dose to critical or-
gans. Mattes et al.6 have demonstrated a significant correlation be-
tween the ROP/BOP–PTV overlap and the dose sparing of that or-
gan in VMAT prostate treatments. A similar method can be applied
to other VMAT treatment sites such as head and neck. Tol et al.14
applied a predictive DVH to auto-planning for individualized qual-
ity assurance setup in head and neck patients using VMAT treat-
ment and managed to lower the salivary gland, oral cavity, and
swallowing muscle mean dose by 3, 5, and 7 Gy, respectively. Some
cancer care centres in Australia have also come to a similar conclu-
sion by using different analysis methods. Caine et al.7 concluded,
when using classification and regression tree (CART) analysis that
the ROP and BOP have a strong predictive ability in IMRT and
VMAT prostate plans. The principle of using the OAR–PTV overlap
to assess adequate DVH parameters can be extended to other treat-
ment modalities such as Tomotherapy and other treatment sites
such as head and neck and prostate with nodal treatment.7 , 15 Yang
et al.16 used predicted R/B doses to set up planning objectives in
an automatic treatment planning system for 5-field IMRT prostate
treatment and achieved acceptable clinical plans.
The selection of gantry angles, collimator angles and number of
arcs were not considered variables in this study. It is the planner’s
choice to choose appropriate technique settings in the planning
software to fulfil the planning goals as long as the settings com-
ply with the departmental prostate VMAT planning protocol. PTV
margins might also vary between doctors and centres. Our results
are based on the ROP/BOP. Different PTV margins might lead to
different ROV/BOV. However, ROP/BOP is a relative measure which
takes into account the overlapping volume as well as PTV volume.
The results of this study can be applied to all centres using the
same planning goals and OAR constraints. Different planning sys-
tems might have different calculation algorithms, but they should
be able to create similar treatment plans that are clinically approv-
able.
As this is a retrospective study, the recruited VMAT plans are
from planners with variable planning experience. A more experi-
enced planner might be able to achieve lower R/B doses than a
novice when planning with large R/B-PTV overlaps. By using differ-
ent optimisation methods, some unachieved planning goals might
have been improved. The quality of the plan can also be affected
by planning time constraints due to radiation-oncology-specified
timeframes. A validation cohort of 5 patients has been investigated
to assess the changes in OAR doses when applying the predictive
equations determined in this project. We found that the OAR DVHs
of the validation plans were consistent with those of the origi-
nal plan. By using the estimated OAR target, the volume of rec-
tum/bladder receiving >78 Gy were reduced in 4 out of 5 cases.
Therefore, it is feasible to apply the results of this study in the
clinic setting in terms of streamlining plan quality and improving
planning efficiency, regardless of planner experience.
With an increasing number of departments implementing an
automated planning program or knowledge based planning system,
 M. Chao, N. Coburn and E. Cosgriff et al. / Medical Dosimetry 46 (2021) 269–273
our predictive model is a precursor to more advanced versions of
planning system. The predictive model provides customized plan-
ning goals that are more realistic based on overlapping percentage.
On the other hand, for centres that have not invested in autoplan-
ning, this tool improves prostate VMAT plan quality and planning
efficiency.
Conclusions
The extent of the overlap between the R/B and PTV in VMAT
prostate radiotherapy has an impact on the radiation doses re-
ceived by these 2 organs. ROP and BOP are stronger predictive
factors than the ROV and BOV especially in the high-dose region
of each organ’s DVH. Cut-off values and 95% prediction intervals
can be used for personalised planning based on individual patient
anatomy characteristics, as opposed to applying generic planning
techniques.
Declaration of Competing Interest
The authors declare no conflicts of interest.
Ethical Standards
NBMLHD Human Research Ethics Committee (HREC).
Acknowledgments
The authors acknowledge Rachael Beldham-Collins and Andrew
Martin for their assistance in this project. This research did not re-
ceive any specific grant from funding agencies in the public, com-
mercial, or not-for-profit sectors.
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