Sean Ferguson

Case Study Spring 2018

April 7, 2018

IMRT Prostate Plan for Patient Enrolled in RTOG 0924 Clinical Trial

History of Present Illness: The patient, RC, is a 76-year-old male of reasonably good health

who has been followed for progressively rising PSA readings since 2014. His PSA reading in

2014 was 2.8 and increased to 4.68 in 2016. Both PSA readings were completed in Nevada and

only a brief medical discussion is included in his current records with Bassett Healthcare.

RC had an initial urology consult at Bassett Healthcare in November of 2016 to discuss

his most recent PSA test results. The urologist discussed possible reasons for the elevated PSA as

well as next steps of care based on the PSA reading and The American Urological Association

recommendations. A Sexual Health in Men (SHIM) questionnaire1 was completed to assist in the

discussion of care. It was decided that an updated and local PSA reading combined with a second

consult was the most appropriate course of action. An updated PSA was obtained, and RC

returned to the urologist to discuss the result on January 3, 2017. The new PSA reading increased

to 5.90. Reasoning for the rising PSA and recommendations for next steps of care were again

discussed. The urologist recommended a biopsy of the prostate to screen for cancer. The

pagreed, and biopsy was scheduled for February 16, 2017.

At his point in RC’s plan of care, RC seemed to become either unsure of instructions or

somewhat unwillingly to seek further results. The February 16, 2017 biopsy is cancelled by RC.

RC claims that he accidently took ibuprofen the night before against recommendations. A new

biopsy was scheduled for March 30, 2017but cancelled by RC due to complaints of flu-like

symptoms. The biopsy was rescheduled for April 28, 2017 but again cancelled by RC because of

claims that the pre-surgical medication that was prescribed was causing his flu-like symptoms to

continue. The urologist phoned RC and assured him that the medication was not causing his

symptoms and offered to prescribe alternative medication. RC opted to continue with current

medication but stated he would not be available to reschedule until the end of June. The biopsy

was rescheduled for June 24, 2017. The urologist explained that at this point, the procedure

would be based on 6 months old tests, but the biopsy is still crucial for diagnosis. The option to

re-draw blood for an updated PSA was also discussed. RC opted for the rescheduled biopsy. RC

arrived for the 6/24/17 biopsy appointment. The procedure is explained to RC, informed consent

is obtained, and the procedure begins. Upon insertion of the ultrasound probe into the rectum,

RC states that the pain is unbearable and does not wish to continue. The procedure is terminated.

The urologist discusses options for a biopsy under anesthesia which will need to be schedule in

the future. RC states that he will be going on vacation and will not be available until September.

The biopsy is rescheduled for September 8, 2017.

RC arrives for the 9/8/17 biopsy. The procedure is explained to RC, informed consent is

obtained, anesthesia is administered, and the procedure begins. Twelve ultrasound guided

samples are taken from the prostate. Samples are obtained from the base, middle and apex of the

prostate as well as the lateral and mid-lateral positions from the right and left sides of the gland.

A total of six cassettes are sent to pathology. The pathology results in a diagnosis of intermediate

risk adenocarcinoma of the prostate with a Gleason score of 3 + 4 = 7. The results of the biopsy

were discussed with RC. Treatment options were discussed which included surgery and short-

term androgen deprivation plus external beam radiation therapy (EBRT).

On October 2, 2017 RC arrived for a radiation oncology consult. The results of his biopsy

as well as the treatment options outlined above were discussed. The radiation oncologist

discussed the National Comprehensive Cancer Network (NCCN) guidelines3 with RC. A detailed

explanation of EBRT was discussed which included the CT simulation procedure as well as the

benefits and recommendation of the use of SpaceOAR4 hydrogel to reduce the risks of rectal

toxicity, MRI to aid in the accuracy of identifying the prostate and organs at risk (OAR), and the

implantation of gold fiducial markers into the prostate to aid in daily prostate localization.. It was

also explained to RC that he is a candidate for clinical trial 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.5 RC requests time to consider hos options. A follow-up consult is scheduled for November

29, 2017.

RC elects for androgen deprivation + EBRT and returns for the follow-up radiation

oncology appointment. The radiation oncologist again explains the steps and procedures. RC opt

to enroll in RTOG 0924. RC is schedule for an immediate Lupron injection per RTOG 0924 and

a return visits are scheduled for SpaceOAR, MRI, fiducials, and CT simulation.

Past Medical History: RC presented with a limited medical history. Aside from his elevated

PSA readings in 2016, RC has a history of gout from the 1990’s as well as a basal cell carcinoma

skin lesion that was surgically removed in 2014. RC also has a history of hypertension and an

episode stroke in 2012.

Social History: RC is a retired casino worker who worked in both Reno and Las Vegas, NV. He

is married with no children. RC is an active drinker who confesses to consuming six beers per

day. He is a former smoker with a 30+ pack year history and is an active occasional smoker of

marijuana. Both his mother and father have a history of hypertension and heart failure and both

have a history of melanoma. There is has no noted sibling history in his records.

Medications: The following medications were reported by RC at the time of consult;

Alloprurinol to control uric due to his history of gout and Alprazolam for anxiety. Bicalutamide,

Ciproflaxin HCL, Leuprolide Acetate were prescribed to RC as part of the androgen-deprivation

regimen to control his prostate cancer. These medications are consistent with the protocol

established in RTOG 0924.

Diagnostic Imaging: No diagnostic imaging was required for workup of his disease however an

MRI was ordered as part of his treatment simulation and planning to aid in the identification of

the prostate and other OAR to be discussed in future section.

Radiation Oncology Recommendations: RC elected to enroll in RTOG 0924. The radiation

oncologist explained the rational and justification of the study. The RTOG 0924 was designed to

study whether prophylactic androgen deprivation plus whole pelvis radiation therapy will

provide better overall survives versus androgen deprivation plus EBRT to only the prostate and

seminal vesicles. The study also hopes to identify differences in acute and long-term events

associated with each approach as measured by quality of life indicators. There is considerable

debate within the medical community as to which approach provides the best overall outcome to

the patient. RC was randomly enrolled in Arm 2.

The Plan (Prescription): RC was randomly selected for Arm 2 of RTOG 0924 and therefore

will is schedule to receive 4500cGy for 25 fractions (180 cGy/fraction) to the whole pelvis and

then an additional 3420 cGy to just the prostate and seminal vesicles for 19 fractions

(180cGy/fx). This represents a combined total dose to the prostate and seminal vesicle of 7920

cGy over 44 fractions.

Patient Setup/Immobilization: On January 24, 2018 RC arrived for the placement of the

SpaceOAR hydrogel injection and placement of the gold fiducial seeds. For this procedure, RC

was placed in a semi-reclined position with legs apart and feet placed in stirrups. A trans rectal

ultrasound probe was inserted into the rectum. The SpaceOAR two-part gel is injected, under

ultrasound guidance, through the rectourethralis muscle in the perirectal space between the

rectum and the prostate. This gel creates additional spacing between the prostate and the rectum

to reduce the potential dose to the rectum which in turn reduces the risks of rectal toxicity. Once

the SpaceOAR injection was completed, three gold fiducial markers were inserted into the

prostate, also under ultrasound guidance, to aid with daily localization and positioning.

On January 30, 2018, RC returned for an MRI to be used for contouring and organ

identification. After completion of the MRI, RC was CT simulated for treatment planning. For

the simulation, RC was positioned in a head first supine orientation on the CT table. A small

yellow head cushion was placed under head for comfort. RC’s hands were placed on his chest

and a Vac-lok immobilization device was molded for his legs. RC was scanned head first with a

Philips Brilliance Big Bore CT scanner utilizing 2mm slice thicknesses. An isocenter was placed

in the Philips software by the radiation oncologists and external tattoo marking were made on

RC’s skin in an Anterior/Posteror and right and left lateral positions (Figures 1-4).

Anatomical Contouring: The simulation CT data set was imported into the Varian Eclipse

treatment planning system. The MRI from 1/30/18 was fused with the planning CT from 1/30/18

using Varian Velocity to aid in contouring (Figure 5). Contouring of the Organs at Risk (OAR)

was accomplished by the medical dosimetrist using the recommendations and guidelines found

in the RTOG contouring atlas for the male pelvis.6 The organs required by the protocol were to

be name as specified in the protocol and included Femur_L, Femur_R, Bladder, PenileBulb,

Rectum, BowelSpace, and External (body contour). The target volumes were identified and

contoured by the radiation oncologist to include GTV (gross tumor volume of the disease)

CTV_4500, CTV_7920, PTV_4500, PTV_7920, SeminalVesicle, SemVes_Prox (for 3420 boost

plan), and CTVn (pelvic nodes for Arm 2 WPRT) (Figure 6). Allowable margins around the

target organs are defined in the protocol. The protocol also required that NonPTV4500 and

NonPTV7920 were created to measure dose to other tissue. These volumes were defined by the

external volume minus the respective PTVs. Additional contours were added to identify the

SpaceOAR gel and the gold fiducials (Figure 7). A contour peer review by a different oncologist

is accomplished before planning begins.

Beam Isocenter/Arrangement: A 9 field Intensity Modulated Radiation Therapy (IMRT)

arrangement was selected to provide the best coverage to the PTVs while minimizing the dose to

the OAR. The plan was developed in two parts, P1_Prostate Lns to cover Phase 1 which includes

PTV_4500 and P2_Prost Bst to cover Phase 2 and PTV_7920. Isocenter for phases 1 and 2 is

located approximately in the center of the prostate. This coincides with the CT origin placed

during simulation which is also the point triangulated by the external tattoos placed on RC.

Effort was made to maintain this as the isocenter to eliminate the need for shifts from the tattoos

which potentially increase the risk of setup errors (Figures 8-9).

Treatment Planning: The treatment planning was completed using Varian Eclipse treatment

planning system version 11.0. The plan was created to be treated on a Varian 23ix Linear

accelerator. Treatment planning was done in two parts to be consistent with Phase 1 and 2 of the

protocol. The initial (Phase 1) plan was prescribed to a dose of 4500cGy (180cGy over 25 fxs) to

a minimum of 95% of PTV_4500. The PTV_4500 consisted on the volume for the whole pelvis

which included the prostate, seminal vesicles and the pelvic nodes plus a PTV margin as defined

in the protocol. The boost (Phase 2) plan was prescribed to a dose of 3420 cGy (180 cGy over 19

fxs) to a minimum of 95% of PTV_7920. PTV_7920 consisted of just the prostate and seminal

vesicles plus the PTV margin. The combination of the two plans resulted in a dose of 7920 cGy

to the prostate and seminal vesicle and 4500 cGy to the volume defined for the whole pelvis.

Both plans were normalized so that 100% of the dose covers 95% of the PTV utilizing a 9 field

IMRT technique with 6MV beam energy on all fields to accomplish the goals established for

both coverage of the PTVs and limits to the OAR. The PTV minimum and maximum coverage

and dose constraints to the Bladder, Rectum, and PenileBulb were defined in the protocol. For

the dose constraint, the physician restricted the limits to our established departmental constraints

as they were more restrictive then required. This was done to further limit the dose to the OARs.

(Figure 10-14)

Quality Assurance/Physics Checks: The completed plan was peer reviewed by the physician

group. The plan is review consists of a plan evaluation by at least one different oncologist than

the primary oncologist. After review, the plan was signed as planning approved. The plan was

then run through RadCalc for a secondary Monitoring Unit (MU) check. Care is taken to ensure

that an accurate calculation point is used for IMRT plans so that the dose is calculated in an open

area away from field edges. The secondary RadCalc MU check must agree to within 3% of the

planned MU. The plan is then sent for a dosimetry double checked by a dosimetrist other than

the planning dosimetrist. The double checked consists verifying that the field sizes, prescriptions,

MUs, filming intent, treatment parameters, energies, calc. points and dose limits are correct.

Once completed, the plan was then sent to the physicist for IMRT QA. IMRT was accomplished

on the 23ix linear accelerator utilizing a MapCheck 2 diode array. The measure results were

compared with the plan to ensure accurate dose distribution

Conclusion: RC began his EBRT in early February and at the date of this case study was 5

fractions of the boost plan from completions. According to his progress notes, he is tolerating

treatment well with little complaints or complications. Prostate treatments are common and a 9

field IMRT plan is straightforward from a dosimetry point of view. I chose this case to expose

myself to the RTOG 0924 trial to better understand the goals and the slight difference from a

standard, low risk prostate case. Prior to my exposure to RTOG 0924, I had overheard an

oncologist mention how important this study was because it is a question that really needs to be

answered. I had the opportunity to interview one of the Radiation Oncologist to speak to him

about the purpose of the study and he explained to me that there are widely varying opinions on

the correct approach to treating unfavorable intermediate risk and favorable high-risk prostate

cancer. NCCN prostate cancer treatment recommendations are based on the risk category that the

patient falls into. There are now seven risks groups ranging from very low risk (lowest) to

regional disease (highest). All risk groups have explicit recommendation for either

prophylactically threating or not treating the pelvis nodes with the exceptions of the unfavorable

intermediate risk and the high-risk groups. In these two groups, which are the groups included in

RTOG 0924, there is no recommendations other than the treating of the nodes “can be

considered”3.

This case study has given me the opportunity to greatly enhance my understanding of the

approaches to the treatment of prostate cancer. My understanding of the why we chose to treat

pelvic nodes or why we may not will be an invaluable piece of knowledge as I continue in my

study of dosimetry. From a planning prospective, prostate treatments can sometimes seem

routine. There is still much that I must learn about the nuances that go into making an IMRT plan

look routine. I intend to apply both my understanding of the conclusions that will hopefully be

drawn from RTOG 0924 and my close observation of the planning process into future plans.

References

1. Erectile Dysfunction and Prostate Cancer: The SHIM Questionnaire. PCF Website.

https://www.pcf.org/c/the-sexual-health-inventory-for-men-shim-questionnaire/.

Published January 25, 2018. Accessed April 7, 2018.

2. What is a Gleason Score? Prostate Cancer Foundation. PCF.

https://www.pcf.org/c/gleason-score/. Published March 16, 2018. Accessed April 7,

2018.

3. NCCN Guidelines for Patients® Prostate Cancer.

https://www.nccn.org/patients/guidelines/prostate/files/assets/basic-html/page-1.html#.

Accessed April 7, 2018.

4. What is SpaceOAR® Hydrogel? SpaceOAR Hydrogel. https://www.spaceoar.com/what-

is-spaceoar-hydrogel/. Accessed April 7, 2018.

5. Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate

Cancer ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01368588?term=rtog

0924&rank=1. Accessed April 7, 2018.

6. RTOG. Male RTOG Normal Pelvis Atlas.

https://www.rtog.org/CoreLab/ContouringAtlases/MaleRTOGNormalPelvisAtlas.aspx.

Accessed April 8, 2018.

Figures

Figure 1. Yellow headrest and hands on chest for simulation

Figure 2. Patients feet in Vaclok.

Figure 3. Anterior tattoo marking.

Figure 4. Left Lateral Tattoo Marking.

Figure 5. MRI fused with planning CT for contouring.

Figure 6. RTOG 0924 contour requirements

Figure 8. AP Isocenter with contours

Figure 9. Right Lateral Isocenter with contours

Objectives

Importance Target Goal (Gy) Coverage Min (%) Max (%) Achieved (%)

1 PTV4500 4595% Dose to cover

100% of the PTV95% 110% 99.9.%

1 PTV 7920 79.295% Dose to cover

100% of the PTV95% 107% 99.9%

Constraints

Importance Target Limit (Gy) Constraint ( %) Max (Gy) Achieved (Gy)

2 Rectum 40 35       34.6%

            60 25       10.9%

            65 17       7.5%

            70 15       4.3%

            75 12       1.6%

3 Bladder 40 50       33.4%

            65 25       16.2%

            70 20       13.2%

            75 15       9.9%

            80 10       2.2%

4 Femoral Head (Each) 50 10       Rt= 0.04%

5 Penile Bulb Mean <52.5       20.5 Gy

6 Bowel 32 40       15.6%

            45 <150cc       10.cc

            50 0       Max= 49.7Gy

Figure 10. Constraint sheet based on total dose of 7920 cGy

Figure 11. Axial isodose at isocenter

Figure 12. Frontal isodose at isocenter

Figure 13. Sagittal isodose at isocenter

Figure 14. Plan Sum DVH for 7920 cGy