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Clinical Oncology Assignment

Jenna Payne
April 26, 2024

Introduction
The patient is a 66-year-old male who initially presented to urgent care in 2023 with
hematuria, dysuria, and a PSA of 8.10 nanograms per milliliter (ng/mL). He was treated with
Bactrim which resolved the urinary symptoms; however, his PSA remained elevated at
6.31ng/mL a few months later. A subsequent biopsy revealed a Gleason score of 3 + 5 = 8
adenocarcinoma with 11 of the 15 cores positive for disease. Additional imaging studies
demonstrated no evidence of nodal or distant metastatic disease and multiparametric magnetic
resonance imaging (mpMRI) results provided a final clinical stage of high-risk, stage IIIB (cT3a,
cN0, cM0, Grade Group: 4) adenocarcinoma of the prostate. A clinical stage of T3a indicates
extraprostatic extension that does not invade adjacent structures.1 The patient reported once
nightly nocturia and only rare occurrences of urinary symptoms such as incomplete emptying of
the bladder, frequency, urgency, and weak stream.

Radiation Prescription
This patient received consultations for both surgical and radiation therapy interventions
and chose to proceed with androgen deprivation hormonal therapy (ADT) and definitive external
beam radiation therapy (EBRT) with a low-dose rate (LDR) brachytherapy boost. He was
prescribed 46gray (Gy) to the prostate and pelvic nodes which was to be delivered in 23 fractions
at 2 Gy per fraction. After finishing this course of treatment, the patient later received permanent,
interstitial LDR brachytherapy to the prostate, prescribed to 100 Gy with Palladium-103 seeds.
This course of treatment was presented as an option due to the patient’s high-risk of recurrence
following the National Comprehensive Cancer Network (NCCN) guidelines.1 The ASCENDE-
RT clinical trial demonstrated that patients diagnosed with intermediate or high-risk prostate
cancer, who received LDR brachytherapy boost following initial pelvic/prostate EBRT, were half
as likely to experience biochemical failure when compared to patients who received a dose
escalated EBRT boost.2 Utilizing LDR brachytherapy boosts allows for doses to be prescribed
that are 1.5-2 times higher than EBRT alone, which is more limited due to constraints of nearby
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normal structures. These increased doses of brachytherapy offer up to 3 times greater biologic
effective dose (BED), which is shown to predict better clinical outcomes in these patients.
Although effective, the ASCENDE-RT trial did report worse acute and late genitourinary (GU)
symptoms in the group of patients that underwent the brachytherapy implant.3 The patient was
provided this information as well as risk factors and side effects of all treatment options during
his consultations to make an informed decision. The forthcoming information provided will
discuss the EBRT portion of this patient’s treatment.

Simulation
A computed tomography (CT) simulation was scheduled, and the patient received
instructions to have a bowel movement prior to the appointment, then arrive with a comfortably
full bladder. This preparation is necessary for planning and treatment because changes in rectal
and bladder fill can significantly change the prostate’s location within the pelvis and it also aims
to decrease side effects and toxicity. An empty rectum and full bladder will reduce the volume of
each receiving the high treatment doses and a full bladder also shifts the small bowel away from
the irradiated volume. On the day of CT-simulation, after the patient’s preparation was
confirmed, he was given 2 pillows then positioned head-first and supine on the scanning table.
The patient held onto a ring across his chest and the Vac-Lok bag beneath him was molded
around his legs and feet to capture his position. This exact setup was documented and the Vac-
lok stored for this patient to ensure a reproducible setup for daily treatment. The CT was then
acquired using 2 mm slices from the second lumbar vertebrae (L2) through the entire pelvis to
include the upper femurs.

Treatment Planning Targets and OAR

The CT-simulation data set was imported into the treatment planning system (TPS) and
fused with T1 and T2 axial slices of the patient’s most recent MRI. The prostate and seminal
vesicles were then contoured utilizing the enhanced soft tissue visualization from the MRIs and a
clinical target volume (CTV_High) was defined as the prostate + seminal vesicles. An additional
CTV was created for nodal volumes (CTVn) which would be combined with CTV_High to
create CTV_pelvis. The planning target volume (PTV) is defined as the CTV_pelvis + a 0.5 cm
margin (Figure 1). This is further explained under the Anatomical Boundaries section.
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The organs at risk (OAR) contoured for this treatment included the bladder, rectum,
bilateral femoral heads, small bowel with potential bowel space, and the penile bulb (Figure 1).
The desired dose constraints for OAR are shown below as well as QUANTEC
recommendations.4 The prescription for this patient’s EBRT (46Gy) is lower than typical dosing
due to his course of treatment including a brachytherapy boost. Therefore, the QUANTEC values
found do not necessarily apply. The clinical protocol followed, during the planning of this
treatment, adapted constraints to better represent the desired sparing of OAR (Table).

Table. OAR Planning Objectives and Outcomes

Normal Desired planning Treatment plan QUANTEC Contraindications of
structure/OAR objectives outcome recommendations4 exceeding OAR tolerances5
Bladder V47Gy < 25% V47Gy = 3.22% V80Gy <15% Grade ≥3 late toxicity:
V43Gy < 35% V43Gy = 17.55% V75Gy < 25% Severe frequency and
dysuria,
V37Gy < 50% V37Gy = 29.52% V70Gy < 35% Frequent hematuria,
V65Gy < 50% Reduction in bladder
capacity,
Severe telangiectasia
Rectum V43Gy < 15% V43Gy = 10.34% V75Gy < 15% Grade ≥2&3 late toxicity:
V40Gy < 25% V40Gy = 12.87% V70Gy < 20% Diarrhea (requiring
parasympatholytic drugs or
V37Gy < 35% V37Gy = 15.25% V65Gy < 25% parenteral support),
V34Gy < 50% V34Gy = 17.77% V60Gy < 35% Severe mucous or bloody
discharge,
V50Gy < 50% Obstruction
Femoral Heads V21Gy < 50% V21Gy = 33.71 Fracture,
Joint stiffness/pain
V23Gy < 40% V23Gy = 28.31

Small Bowel V45Gy < 65cc V45Gy = 65.07 V45Gy < 195cc Grade ≥3 enteritis:
V40Gy < 100cc V40Gy = 115.82 Weight loss,
Bowel stricture,
V35Gy < 180cc V35Gy = 173.53 Bowel obstruction,
D0.03cc < 5000cGy D0.03cc = 4808.13cc Ulceration,
Bleeding
Penile Bulb V40Gy < 50% V40Gy = 66.11% Mean dose to 95% Severe erectile dysfunction
of volume < 50Gy
D70 ≤ 70Gy
D50 ≤ 50Gy
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Figure 1. Contours of PTV and OAR

A Axial view

B Sagittal view C Coronal view

Treatment contours are outlined in multiple planes: PTV (shaded green), small bowel space (magenta), bilateral femoral heads (orange),
bladder (yellow), rectum (blue), and the penile bulb (light purple).
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Lymph Nodes
The CTVn was contoured to include the external, internal, and common iliac lymph
nodes, as well as the presacral and obturator nodes. Although this patient presented clinically as
node negative, his 3 + 5 = 8 Gleason score (Grade Group: 4), staging, and 11/15 positive biopsy
cores classified his cancer as high-risk. According to NCCN guidelines and RTOG 0924,
prophylactic pelvic lymph node irradiation is recommended for patients with high-risk prostate
cancer.1,6 In a consensus gathering of specialized GU Radiation Oncologists, data presented
showed lymph node drainage to the previously mentioned nodal areas and alluded that during
dissection, as more lymph nodes are removed, more would be found positive.7 Based on
Briganti’s (2012) nomogram, this patient has a 66% calculated probability of lymph node
involvement based his disease characteristics.8 For these reasons, this patient did receive
prophylactic nodal irradiation with EBRT (Figure 2).

Anatomical Boundaries
The CTV_high and CTVn volumes were combined with a Boolean operation to create a
CTV_pelvis. According to RTOG 0924, the superior border of this volume was to include the
sub-aortic common iliac nodes which begin at the aorto-iliac bifurcation which typically
corresponds to the level of L4-L5. For this patient, the location of the bifurcation was slightly
superior to this associated vertebral level. The CTV_pelvis includes a 7 mm margin around the
iliac vessels and extends laterally beyond the pelvic brim at least 1 cm. Inferiorly, the entire
prostate must be included, as is the extent of the external iliac and obturator lymph nodes, at the
top of the femoral heads and pubic symphysis, respectively. Posteriorly, the border includes the
presacral nodes from about S1-S3, splitting the sacrum at about S3 to reduce rectal dose. The
anterior border is drawn to the pubic symphysis to include the full obturator nodal area and must
include the anterior portion of the external iliac node and prostate.9 The CTV_pelvis was then
given a 0.5cm margin, defining the PTV. A visualization of the PTV anatomic boundaries is
demonstrated in Figure 3.
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Figure 2. Nodal Volumes Included in Whole Pelvis EBRT
A Volume containing common iliac nodes B Volumes containing internal and external iliac nodes

C Volume containing presacral nodes D Sagittal view of presacral and common iliac nodes

E Volumes containing obturator nodes

B) Pink arrow indicates region of internal iliac lymph nodes. Green arrow indicates region of external iliac lymph nodes. D) Yellow arrow
indicates region of common iliac nodes. Blue arrow indicates region of presacral nodes. E) Red ovals indicate regions of obturator nodes.
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Figure 3. Anatomical Borders of PTV (green)

RT Treatment Technique
Volumetric modulated arc therapy (VMAT) was the technique chosen to deliver this
patient’s EBRT treatment, utilizing a combination of 2 partial and 2 full arcs, and an energy of 10
megavolts (MV) for all beams. There are often field size limitations when employing multi-
collimator leaves (MLCs), which are located along the X-jaws. To not exceed these limitations,
the fields for each arc split the PTV. The first partial arc started at 181 degrees moving clockwise
ending at 0 degrees. The second continues this trajectory beginning at 0 degrees and ending at
179 degrees. Both partial arcs have the collimator set at 23.7 degrees to reduce the interleaf
radiation transmission. The fields for these partial arcs split the PTV from right/left as seen in
Figure 3, to ensure individual MLC leaves did not overextend into the fields. The third and
fourth arcs were full arcs, each traveling 358 degrees counterclockwise and clockwise,
respectively, with 2-degree spacing between control points. The collimator was set at 92 degrees
for these full arcs and the fields split the PTV in the superior and inferior direction (Figure 4).
Changing the orientation of how the PTV was split allowed for the MLCs to be utilized in tissue
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sparing from different vantage points while still ensuring adequate coverage of the PTV from the
overlap in the fields.

Figure 4. Field Parameters

A Arc 1: 181°- 0° B Arc 2: 0°- 179°

C Arc 3: 179°- 181° D Arc 4: 181°- 179°

Once the geometry was set for radiation delivery, optimization was used to define dose
constraints and control overall dose distribution within the plan. Specific optimization structures
had been created during the contouring process after the definition of the target volumes. The
PTV_OptiPelvis is an expansion of the PTV, superiorly and inferiorly by 0.3 cm, laterally and
anteriorly by 0.2 cm, and no expansion posteriorly to avoid the rectum. This structure assists in
ensuring adequate coverage to the actual PTV, especially superiorly/inferiorly. During
optimization high-priority objectives can be set for this optimization structure to match or exceed
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PTV objectives, and though they likely will not be met for the PTV_OptiPelvis, the actual PTV
within this structure is better able to meet its desired objectives. The Recto_PTV_OVL and
Bladder_PTV_OVL structures removed rectum and bladder, respectively, from extending into
the PTV by a margin of 0.4 cm. Both were created to enable better sparing of their associated
structures during optimization while not compromising PTV coverage.

Final DVH and Plan Evaluation

The final dose volume histogram (DVH), showing target and normal structures for this
EBRT treatment plan, is displayed in Figure 5. Following the RTOG 0924 protocol, the plan was
normalized to have 98% of the PTV receiving 100% of the prescribed dose of 46 Gy and the
minimum dose to the PTV was 4303.4cGy. The maximum PTV dose (Dmax), defined as the
dose to a volume of 0.03 cubic centimeters (D0.03cc) was about 4825cGy, which was less than
the protocol’s allowed Dmax of 5060cGy.6 Meeting these coverage objectives indicates this is a
quality VMAT plan with acceptable homogeneity. The dose constraints for all OAR were met
apart from the penile bulb (V40 Gy < 50%) and small bowel space (V45 Gy < 65cc and V40 Gy
< 100cc). These parameters were discussed with the prescribing radiation oncologist to
determine if further efforts were needed to meet these constraints. The physician’s stance aligned
with the RTOG 0924 protocol, regarding the penile bulb constraint as a guideline which should
not compromise PTV coverage.6 Also, due to (1) the physician’s desire to include the common
iliac nodes extending to the aorto-iliac bifurcation, rather than commencing at the L4-L5
interspace, (2) the small bowel contour including potential bowel space, and (3) the treatment
plan’s values for these constraints being only slightly greater than the desired values, he was
lenient on meeting these constraints and approved the plan.
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Figure 5. Final DVH

PTV
CTV
Femoral Penile Bulb High
Heads

Rectum
Small Bowel Bladder
(Space)

DVH demonstrating the target volumes and OAR. The crosshair (dark blue line) is indicating that 98% of the PTV is receiving the
prescribed dose of 4600cGy.

Conclusion
There are many aspects to consider during the development of a treatment plan in
radiation oncology. Accurate delineation of treatment volumes, OAR, and other normal tissues is
a crucial process that ensures appropriate evaluation can occur. Understanding capabilities and
limitations of the equipment used to deliver radiation is not only useful in creating optimal plans
but also for solving issues with undesirable dose distributions, such as the elimination of hotspots
or increasing coverage to target volumes. Simple adjustments to the geometry of the gantry,
collimator, or couch may also enable improvements in a treatment plan. Patient comfort is
another detail to regard when determining the best treatment technique. For example, this patient
was required to have a full bladder prior to and for the duration of his treatment, which becomes
more complicated as his side effects worsen. The use of VMAT, instead of static beam IMRT that
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usually requires 8+ beams, reduces the total time of treatment and limits the likelihood of
intrafraction changes, such as bladder loss or patient movement. Every component of this
planning process requires vigilant attention to detail to avoid any undue harm to patients and to
ensure they receive high quality care throughout their full courses of treatment.

References
1. Schaeffer EM, Srinivas S, Adra N, et al. NCCN clinical practice guidelines in oncology
(NCCN guidelines®: prostate cancer. Published March 8, 2024. Accessed April 26, 2024.
https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

2. Riegel AC, Nosrati JD, Sidiqi BU, et al. Determining combined modality dosimetric
constraints by integration of IMRT and LDR prostate brachytherapy dosimetry and
correlation with toxicity. Adv Radiat Oncol. 2022; 8(3)101156.
doi.org/10.1016/j.adro.2022.101156

3. Stish BJ, Davis BJ, Mynderse LA, McLaren RH, Deufel CL, Choo R. Low dose rate prostate
brachytherapy. Transl Androl Urol. 2018; 7(3). doi.org/10.21037/tau.2017.12.15

4. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative analyses of normal tissue effects in
the clinic (QUANTEC): An introduction to the scientific issues. Int J Radiat Oncol Biol
Phys. 2010;76(3). doi:10.1016/j.ijrobp.2009.09.040

5. Choa KSC, Perez CA, Wang TJC. Late effects of cancer treatment and the QUANTEC
review. Radiation Oncology: Management Decisions. 4th ed. Philadelphia, PA: Wolters
Kluwer; 2019:117-135.

6. Roach M, Hsu I-C, Chung H, et al. RTOG 0924 - androgen deprivation therapy and high
dose radiotherapy with or without whole-pelvic radiotherapy in unfavorable intermediate or
favorable high risk prostate cancer: a phase III randomized trial. Published December 13,
2018. Accessed April 26, 2024. https://www.vumc.org/radiation-oncology/sites/vumc.org.
radiation-oncology/files/RTOG0924-URO%20R0924%20Protocol%20Amendment%205%
202018DEC13_Change%20Memo%20for%20Protocol%20and%20Consent%20Form.pdf

7. Lawton CAF, Michalski J, El-Naqa I, Buyyounouski MK, et al. RTOG GU radiation

oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate
cancer. Int J Radiat Onocol Biol Phys. 2009; 47(2):383-387.
doi.org/10.1016/j/ijrobp.2008.08.002

8. Predicting lymph node involvement in prostate cancer patients. Evidencio Medical Decision
Support. Updated 2015. Accessed April 26, 2024.
https://www.evidencio.com/models/show/797
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9. De Hertogh O, Le Bihan G, Zilli T, et al. Consensus delineation guidelines for pelvic lymph
node radiation therapy of prostate cancer: on behalf of the francophone group of urological
radiation therapy (GFRU). Int J Radiat Oncol Biol Phys. 2023; 118(1):29-40.
doi.org/10.1016/j.ijrobp.2023.07.020