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Offline Adaptive Radiation Therapy in the Treatment of Prostate Cancer

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

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 These organs at risk (OR) are highly mobile,
morphing shapes that can make dose delivery highly speculative, creating questionable dose to
the OR. Even as sophisticated as the plans have become for radiation therapy, they cannot
account for daily changes in patient anatomy.3
Adaptive radiation therapy (ART) has been around for decades.3 However, technical
complications can make ART difficult to come to fruition, namely the timely efforts in
recontouring and re-planning each patient who is receiving radiation therapy treatment.3 Cone
beam CT (CBCT) 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 genitourinary (GU) and gastrointestinal (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
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regular reports be completed on the received dose to the planning organ 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.7 MIM software has been utilized in an
accurate and automated ART workflow in conjunction with methods that use deformable CBCT
contours.6 The goal of this research is 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 retrospective as well as prospective manner. Each
patient had to have a diagnosis of 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.
For the simulation, patients were placed in the supine position with a pillow under the
head and arms high on 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 had to empty the rectum and fill the 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 treatment planning system (TPS) or
Varian Eclipse 13.7 TPS. The clinical target volume (CTV) was contoured by the physician on
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the CT dataset. The planning target volume (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

The treatment goals, as specified by the physician, 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. Patient 2 was treated to the prostate fossa using static IMRT with a nine-beam
arrangement. 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 RTOG were used for the intact prostate plans,
and QUANTEC as well as RTOG constraints were using for prostate fossa plans. The specific
dose volume constraints can be found in Table 2. For example, V6550% means that no more
than 50% of the OR volume can receive more than 65 Gy.
For each patient, the daily CBCT was completed and imported into MIM software, where
shift information was updated, to be analyzed. The software then automatically fused the CBCT
with the planning CT and deformed and transferred the contours. These contours were reviewed
and, if necessary, edited by the 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.
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Plan Analysis and Evaluation

Patient 1 was analyzed retrospectively for all 30 treatment fractions. The comparative
cumulative dose-volume histogram (DVH) showed significant variations in the actual delivered
dose when compared to the planning dose (Figure 1). The PTV coverage was less than
anticipated, with only 74.81% 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.
The dose to the rectum was also significantly lower than planned, with 15% of the volume
receiving 31.13 Gy vs. 52.63 Gy. Doses to the CTV and bladder were 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
received less dose than planned, 95% of the dose received by 88.8% of the volume vs. the
planned 98.29% of the volume. The dose received by 15% of the rectum was 48.99 Gy, which
was lower than the planning dose of 51.46 Gy. The dose to the bladder was higher for the 60% of
the volume, 46.52 Gy vs. 39.75 Gy.
The reports were generated for each daily fraction for all the patients. The DVH was
created showing the variations between planning doses and actual single fraction doses. Daily
variations of dose received by the OR as well as daily variations in OR volume were also
recorded. Figures 3a-b show the daily OR dose variations for 15% of the organ volume and
figure 3c shows the daily OR volume changes for Patient 1. Figures 4a-4c show the same
information for Patient 2.

Conclusion

For each patient, there were notable variations when comparing planning dose with the
actual dose delivered to the target and OR on the daily basis. 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. 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, rendering the software most useful for the patients that are currently on
treatment, as analyzing all the CBCTs retrospectively has proven to be too time consuming.
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
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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.
Since the software keeps track of 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. 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 seen 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 Dos.
2015;40:222-225. 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
Dos. 2014;39:38-43. http://dx.doi.org/10.1016/j.meddos.2013.09.003
6. 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.
7. 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. http://dx.doi.org/10.1088/0031-9155/55/1/005
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Figures

Figure 1. Patient 1 - cumulative DVH showing planned dose vs. total delivered dose.
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*will insert when the patient completes tx

Figure 2. Patient 2 - cumulative DVH showing planned dose vs. total delivered dose.
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Figure 3a. Daily variations of dose received by 15% of the rectal volume for Patient 1.

Figure 3b. Daily variations of dose received by 15% of the bladder volume for Patient 1.
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Figure 3c. Daily variations in OR volumes for Patient 1.

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Figure 4a. Daily variations of dose received by 15% of the rectal volume for Patient 2.

Figure 4b. Daily variations of dose received by 15% of the bladder volume for Patient 2.

Figure 4c. Daily variations in OR volumes for Patient 2.

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Tables
Table 1. Prescription details for Patients 1-3
Case Patient 1 Patient 2 Patient 3
Site Prostate Prostate fossa
Prescription Dose 54 Gy in 30 Fx 50.4 Gy in 28 Fx
Planning Dose VMAT, 2 full arcs IMRT, 9 beams

Table 2. Constraints from QUANTEC and RTOG for OR

QUANTEC RTOG
Bladder V65 50 % V40 70 %
V70 35 % V65 50 %
V75 25 %
V80 15 %
Rectum V50 50% V40 55 %
V60 35% V65 35 %
V65 25%
V70 20%
V75 15%