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Offline Adaptive Radiation Therapy in the Treatment of Prostate Cancer: A Case Study

Authors: Heath Bonsall, B.S., CMD, R.T.(T), Beverly Meyer, B.A., R.T.(R)(T), Evgenia Nigay,
B.S., R.T.(T), Ashley Hunzeker, M.S., CMD, Nishele Lenards, M.S., CMD, R.T.(R)(T),
FAAMD
Medical Dosimetry Program at the University of Wisconsin La Crosse, WI

Abstract
Introduction: The purpose of this case study is to develop a method to account for the
difference in the daily volumes in the bladder, rectum, and targets in prostate radiotherapy and to
compare the predicted dose to the actual dose to these organs.
Case Description: Five patients, both prospectively and retrospectively, were selected from two
different cancer centers with a biopsy confirmed diagnosis of prostate cancer. The patients
planning target volume (PTV) and organs at risk (OR) were contoured on the CT dataset using
either Eclipse or Monaco treatment planning systems (TPSs). Cone-beam CT (CBCT) scans
were collected prior to each daily treatment and exported to MIM software for analysis. The
automatically generated reports evaluated the organ volume changes, the actual dose received
during a single fraction, and the projected dose to each organ at the completion of the treatment
course via comparative cumulative dose-volume histograms (DVHs).
Conclusion: Volume changes in the bladder and rectum can cause notable variations in the
prescribed dose versus the actual dose received. MIM software was proven to have utility
prospectively by tabulating daily dose and projecting final doses, potentially aiding physicians in
decisions about the boost plans, thus making offline adaptive radiation therapy (ART) clinically
manageable.
Key Words: Adaptive radiation therapy, prostate cancer, MIM software

Introduction
Among men in the United States, prostate cancer is the second most common cancer and
one of the most common causes of death.1 Radiation therapy for prostate cancer is a highly
utilized form of treatment in cancer centers throughout the United States. Delivery of a sufficient
dose to the prostate or prostate bed while limiting dose to adjacent radiosensitive structures, such
as the bladder and rectum proves to be difficult.2 Organs at risk are highly mobile, morphing
shapes that can make dose delivery highly speculative, creating questionable dose to the OR.
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Even as sophisticated as the plans have become for radiation therapy, they cannot account for
daily changes in patient anatomy.3
Adaptive radiation therapy has been around for decades.3 However, technical
complications can make ART difficult to come to fruition, namely the timely efforts in re-
contouring and re-planning each patient who is receiving radiation therapy treatment.3 Cone
beam CT is considered to be the standard check utilized for online ART prior to daily radiation
treatments. As studies have shown, the use of CBCT can decrease the acute and chronic side
effects to the GU and GI systems.4
Adaptive radiation therapy can play an important role in decreasing unwanted dose to
critical structures and normal tissues. Prostate bed and intact prostate radiation treatments are
heavily reliant upon proper and consistent bladder filling as well as rectal emptying. When these
two criteria are not adequately reproduced according to the CT planning scan, the dose delivered
to the target can be considerably altered.2 Basing the plan on one CT scan, daily changes in
patient positioning by even a few millimeters can result in deviation from the intended dose.4
The International Commission on Radiological Units and Measurements (ICRU) recommends
regular reports be completed on the received dose to the planning organs at risk volume (PRV),
which is now available through the use of daily CBCT.5
Daily changes in positions of OR and their respective volumes can alter dose
considerably, warranting investigation. Retrospectively analyzing the dose to the target can
reveal a high fluctuation in minimum dose to the prostate.6 MIM software has been utilized in an
accurate and automated ART workflow in conjunction with methods that use deformable CBCT
contours.7 The goal of this research study was to develop a method to account for the actual
difference in the volumes from day to day and to compare the predicted dose to the actual dose
delivered to the bladder, rectum, and targets.

Case Description
Patient Selection
Patients for this study were selected in a retrospective as well as prospective manner.
Each patient was diagnosed with prostate adenocarcinoma confirmed via biopsy. Selected
patients were to have the treatments to the intact prostate with or without nodal involvement or to
the prostate bed.
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For the simulation, patients were placed in the supine position with a pillow under the
head and arms high on their chest, holding a ring. The legs were immobilized in a Vac-lok. Each
patient received a set of permanent marks in the pelvic region, anteriorly and on either side, to
provide a reference point for treatment planning. Radiopaque markers were placed on these
marks to visualize them during the scan. Patients were scanned head first, using 2 mm slices on
either Siemens Emotion 16 or Siemens Somatom Definition AS CT scanner.
As per the clinics protocol, the patients were instructed to empty their rectum and fill
their bladder prior to the simulation and each day before treatment. If the rectum was too full,
patients were asked to have a bowel movement before repeating the scan. Patients were also
instructed to have a low-residue diet for the duration of the treatment to help prevent or reduce
diarrhea.

Target Delineation
Once the simulation scan was complete, the target delineation and treatment planning
were performed using either the Elekta Monaco 5.11.01 TPS or Varian Eclipse 13.7 TPS. The
clinical target volume (CTV) was contoured by the physician on the CT dataset. The PTV was
created by expanding the CTV by 3 mm posteriorly and 5 mm in all other directions for the
intact prostate or 8 mm in all directions for the prostate fossa. Once the CT data set was received
by the medical dosimetrist, OR were contoured. The OR of interest for this study included the
rectum and bladder volumes.
Prior to each treatment, the patients were imaged using CBCT. The scans were matched
to the initial planning CT scan to ensure the precise target location as well as consistency in
bladder filling and rectal emptying during each treatment. The CBCT scans along with any shifts
made were sent to the MIM software for analysis.

Treatment Planning
Specified by the physician, the treatment goals included uniform coverage of the PTV
while keeping the dose to the bladder and rectum as low as possible. The prescription dose
varied depending on whether the target was the intact prostate or the prostate fossa. The
treatment plans were created using either the volumetric arc therapy (VMAT) or static intensity-
modulated radiation therapy (IMRT). Patient 1 was treated to the intact prostate using a two-full
arc VMAT. Patients 2 through 5 were treated using static IMRT with a nine-beam arrangement.
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The prescription for each patient is summarized in Table 1. For the purpose of this study only the
initial plans without the boost were used.
Desired dose to critical structures was not to exceed the guidelines set forth by the
Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) and the Radiation
Therapy Oncology Group (RTOG). Constraints by the RTOG were utilized for both prostate and
prostate fossa plans; additionally, QUANTEC constraints were used for the prostate fossa plans.
As per QUANTEC constraints volume of rectum receiving 50 Gy (V50) cannot exceed 50% of
the total organ volume (V50 50%), volume receiving 60 Gy cannot exceed 35% (V60 35%),
and volume receiving 65 Gy cannot exceed 25% (V65 25%). For the bladder, volume receiving
65 Gy cannot exceed 50% of the organ volume (V65 50%) and volume receiving 70 Gy cannot
exceed 35% (V70 35%). Following the RTOG constraints, volume of the rectum receiving 40
Gy cannot exceed 55% (V40 55%) and volume of the bladder receiving 40 Gy cannot exceed
70% (V40 70%). The summary of the dose volume constraints can be found in Table 2.
For each patient, the daily CBCT was completed and imported into MIM software, where
shift information was updated to be analyzed. The software automatically fused the CBCT with
the planning CT, deformed and transferred the contours. These contours were reviewed and, if
necessary, edited by the medical dosimetrist prior to generating the reports. The reports were
created automatically and provided information on the organ volume changes, planning dose to
each organ compared to the actual dose received during a single fraction, and the projected dose
to each organ at the completion of the treatment course.

Plan Analysis and Evaluation

Patient 1 was analyzed retrospectively for all 30 treatment fractions. The comparative
cumulative DVH showed no significant variations in the actual delivered dose when compared to
the planning dose (Figure 1). The PTV coverage was slightly less than anticipated, with 95.85%
of the volume being covered by 95% of the prescription dose vs. 98.07% of the volume covered
by 95% of the prescription dose during the initial planning. Overall, the actual dose to the
bladder was slightly lower than the planned dose, and the actual dose to the rectum was slightly
higher than the planned dose but without significant variation. Doses to the CTV were also
comparable.
Patient 2 was analyzed while on treatment. The comparative cumulative DVH showed
actual dose delivered to the CTV to be comparable to the planning dose (Figure 2). The PTV
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received less dose than planned, 95% of the dose received by 95.53% of the volume vs. the
planned 98.29% of the volume. The dose received by the rectum was consistent during daily
treatments, but was overall higher than the initially planned dose. The dose to the bladder was
comparable and slightly lower than the planned dose.
The comparative cumulative DVH for Patient 3, who was analyzed while on treatment,
showed a comparable coverage of the CTV and the PTV (Figure 3). The actual dose to 15% of
the rectum was 36.75 Gy, an increase from the planned dose of 32.91 Gy. The rectal volume
overall also received a higher dose than planned. The dose received by the bladder was very
comparable.
Patient 4 was analyzed while on treatment using a hypo-fractionated prescription and
showed no deviation in CTV coverage on the comparative cumulative DVH (Figure 4). The PTV
coverage was reduced from 96.66% of the volume covered by the prescription dose to 91.25%.
The bladder received the dose very similar to the planned dose. The dose to the rectal volume
was higher than planned, with 15% of the volume receiving 43.36 Gy vs. 37.47%.
Patient 5 was analyzed while on treatment. The CTV and the PTV coverage was
comparable between the planned dose and actual received dose (Figure 5). The cumulative dose
to the bladder volume also did not deviate from the initial planned dose. Rectal volume,
however, received a higher than anticipated dose. The dose to 15% of the rectal volume was
43.29 Gy, an increase from 40.55 Gy.
The reports were generated for each daily fraction for all the patients. The DVH created
showed the variations between planning doses and actual single fraction doses. Daily variations
of dose received by the OR were recorded. Overall the dose received by the OR on the daily
basis fluctuated only slightly, with more notable changes recorded in the dose received by the
rectal volume. The greatest variation in dose for the 15% of the rectal volume between all five
patients was 15.72% more dose received than planned. The dose received by 15% of the bladder
volume was 3% less than the planned dose. Daily variations in OR volumes were also recorded
with significant fluctuations from fraction to fraction. Figure 6 shows the variations in bladder
volume between the initial planning CT and each daily fraction for all five patients. Figure 7
shows the daily variations in rectal volume for all patients.
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Conclusion
For each patient, there were notable variations when comparing planning dose with the
actual dose delivered to the target and OR, especially the rectum daily dose. The daily changes in
turn add up to a cumulative dose that differs from the initial planning dose. These findings prove
that there is utility in using the MIM software to track the changes. When completed while the
patients are on treatment, the entire process from uploading the daily CBCT scan into the
software to editing the contours and generating the reports takes between 5 to 10 minutes.
Analyzing all the CBCTs retrospectively was proven to be too time consuming. This renders the
software most useful for the patients that are currently on treatment.
Dose tracking during the initial portion of the plan will provide useful information when
designing the boost plan. Since the actual delivered dose will be available from the initial plan, it
will provide the planner with a better idea of how much dose is still allowable to the OR. The
target coverage can also be adjusted for the boost plan if it was not adequate during the initial
plan. In addition, knowing the actual doses received might aid physicians in deciding whether
further dose escalation is feasible or if the OR would be overdosed. The next step in utilizing the
software could be to re-optimize the plan prior to the daily treatment if the variations are
significant enough.
Since the software monitors daily doses, it takes each fraction into account and not only
compares the daily variations, but also creates a projected final dose. This function of MIM
software makes analyzing the dose delivered on the daily basis very useful. It makes possible for
detecting changes that are so significant that they might prompt another planning scan and a new
treatment plan. Despite some of the software limitations, such as the need to manually edit
deformable contours, the workflows designed by the MIM software engineers make the process
of offline adaptive therapy as automated as possible, making it clinically manageable. Based on
the study findings, the changes displayed during daily treatments as well as the actual cumulative
dose variations justify the extra workload that goes into analyzing the daily CBCTs with MIM
software.
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References
1. Prostate Cancer Statistics. Centers for Disease Control and Prevention Web site.
https://www.cdc.gov/cancer/prostate/statistics. Updated May 23, 2017. Accessed June
21, 2017.
2. Huang TC, Chou KT, Yang SN, Chang CK, Liang JA, Zhang G. Fractionated changes in
prostate cancer radiotherapy using cone-beam computed tomography. Med Dosim.
2015;40(3):222-225. http://dx.doi.org/10.1016/j.meddos.2014.12
3. Lim-Reinders S, Keller BM, Al-Ward S, Sahgal A, Kim A. Online adaptive radiation
therapy. Int J Radiat Oncol Biol Phys. In Press.
http://dx.doi.org/10.1016/j.ijrobp.2017.04.023
4. Tonlaar NY, Marina O, Brabbins DS, et al. Use of weekly cone beam CT for adaptive
radiation therapy decreases toxicity for prostate cancer patients treated with IMRT. Int J
Radiat Oncol. 2013;87(2,Supplement):S176.
http://dx.doi.org/10.1016/j.ijrobp.2013.06.454
5. Prabhakar R, Oates R, Jones D, et al. A study on planning organ at risk volume for the
rectum using cone beam computed tomography in the treatment of prostate cancer. Med
Dosim. 2014;39(1):38-43. http://dx.doi.org/10.1016/j.meddos.2013.09.003
6. Noel CE, Santanam L, Olsen JR, Baker KW, Parikh PJ. An automated method for
adaptive radiation therapy for prostate cancer patients using continuous fiducial-based
tracking. Phys Med Biol. 2010;55(1):65-82. http://dx.doi.org/10.1088/0031-
9155/55/1/005
7. Pirozzi S, Piper J, Nelson A, Shen Z, Gardner S. Evaluation of deformable prostate cone
beam computed tomography (CBCT) contouring methods for adaptive radiation therapy.
Int J Radiat Oncol. 2013;87(2, Supplement):S719.
http://dx.doi.org/10.1016/j.ijrobp.2013.06.1904.
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Figures

Figure 1. Patient 1 - cumulative DVH showing planned dose vs. total delivered dose; 30
fractions (fx).

Figure 2. Patient 2 - cumulative DVH showing planned dose vs. total delivered dose; 28 fx.
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Figure 3. Patient 3 - cumulative DVH showing planned dose vs. total delivered dose; 25 fx.

Figure 4. Patient 4 - cumulative DVH showing planned dose vs. total delivered dose; 20 fx.
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Figure 5. Patient 5 - cumulative DVH showing planned dose vs. total delivered dose; 25 fx.

Figure 6. Daily variations in bladder volume for Patients 1-5 (fx. 0 = initial planning volume).
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Figure 7. Daily variations in rectal volume for Patients 1-5 (fx. 0 = initial planning volume).
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Tables
Table 1. Prescription details for the initial plan for Patients 1-5.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Prostate
Site Prostate Prostate Prostate Prostate
fossa
54 Gy / 30 50.4 Gy / 28 45 Gy / 25 50 Gy / 20 45 Gy / 25
Prescription Dose
fx fx fx fx fx
VMAT, 2 IMRT, 9 IMRT, 9 IMRT, 9 IMRT, 9
Planning Technique
full arcs beams beams beams beams

Table 2. Constraints from QUANTEC and RTOG for OR.

QUANTEC RTOG
V65 50%
Bladder V40 70%
V70 35%
V50 50%
V40 55%
Rectum V60 35%
V65 25%