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Curtis Wilgenbusch February Case Study February 28, 2014 Volumetric Modulated Arc Therapy (VMAT) for Prostate Cancer History of Present Illness: Patient EC is an 82 year-old male with a history of an elevated prostate specific antigen (PSA) dating back to 2006. EC underwent his first prostate biopsy in 2006. At the time of that biopsy, his PSA level was 4.6 nanograms (ng)/milliliter (mL). The biopsy was negative. EC was then followed closely through the years. His PSA originally decreased to 2.2 ng/mL in 2007 but then gradually increased until he was sent for another biopsy in August of 2011 when his PSA reached 5.6 ng/mL. This biopsy revealed that 4 of the 14 cores were positive for adenocarcinoma of the prostate gland. The Gleason score at that time was 6. EC opted for active surveillance. The next documented PSA in July 2013 was 2.7 ng/mL. The patient then underwent his third set of prostate biopsies in August 2013. The biopsy revealed one of 12 cores positive for Gleason 7, involving 30% of the right mid apex. The patient was staged as T1cN0M0 with intermediate adenocarcinoma of the prostate. The patient was referred to the radiation oncology department and met with the radiation oncologist in January 2014 to discuss treatment options. Due to the patient's age and multiple comorbidities, the radiation oncologist did not believe that short-term androgen ablation would benefit the patient. The radiation oncologist recommended external beam irradiation of the prostate with the use of intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Past Medical History: EC has a past medical history of asthma, thrombocytopenia, anemia, epilepsy, umbilical hernias, left eye blindness, right eye cataract, abdominal adhesions, and small bowel obstruction. The patient also has a history of gastric lymphoma, which was treated with chemotherapy in 1993. The patient did not receive radiation therapy for the gastric lymphoma. Social History: EC is originally from Cuba. The patient was in the insurance business but retired a few years ago. The patient is married with two children. EC quit smoking 45 years ago but smoked two packs per day for 25 years. He is a recovering alcoholic who started drinking alcohol at the age of 12 and quit at the age of 37. Medications: EC takes the following medications: Flomax, Ketoconazole, Dilantin, Zantac, Symbicort, and topical 5-Fluorouracil (FU) for the treatment of keratoses.

Diagnostic Imaging: EC had a transrectal prostate ultrasound (TRUS) performed in August 2013. Although there were areas of hyperdense echoes seen that were suggestive of calculi in the capsule, the TRUS did not reveal any hypoechogenic areas suggestive of cancer. The seminal vesicles and bladder were normal. An ultrasound guided biopsy was performed on the abnormal appearing areas in the base, mid-gland, and apex bilaterally. Results of the biopsy revealed adenocarcinoma of the prostate with a Gleason score of 7. The prostatic tissue involved by tumor was roughly 30%. After agreeing with the recommendation for external beam radiation the radiation oncologist sent the patient for a total body bone scan in January 2014. The bone scan did not reveal any evidence of bony metastases. Radiation Oncologist Recommendations: After a review of EC's diagnostic studies, biopsy report, and pathology, the radiation oncologist recommended that EC receive external beam radiation to the prostate. The recommendation included definitive IMRT/IGRT using a volumetric modulated arc therapy (VMAT) technique. Before the introduction of IMRT, the doses delivered via 3-dimensional (3-D) conformal radiotherapy to the organs at risk (OR) were much greater. Higher doses to the OR such as the rectum and bladder increase the likelihood of grade 2 toxicity.1 It has been shown that IMRT can dramatically reduce the doses to small bowel, rectum, bladder, and pelvic bones.2 However, one of the downsides to static field IMRT is the length of time it takes to deliver the complete treatment for several static fields. The VMAT technique has been shown to dramatically reduce the treatment time, which has many benefits including the reduction of intrafraction motion.3 In a study by Quan et al,4 the quality of the VMAT plans were superior to the 8-field IMRT plans used at their institution when comparing dose to the rectum and treatment delivery efficiency. The Plan (prescription): The treatment plan recommended by the radiation oncologist was high dose irradiation of the prostate with IMRT/IGRT utilizing the VMAT technique. This plan was designed to deliver a total of 7740 centigray (cGy) to the planning target volume (PTV) at 180 cGy per fraction, for a total of 43 fractions. The PTV included the prostate gland plus a 0.8 cm uniform margin, with the exception of the posterior aspect of the gland. The posterior margin was set at 0.5 cm due to the close proximity of the rectum. These margins were included to account for uncertainties such as motion and setup errors. Patient Setup / Immobilization: The Philips Brilliance Big Bore CT/simulator (Sim) was used for the simulation. The patient was placed in the supine position with his hips and legs

immobilized in a Civco Vac-Lok cradle (Figure 1). The hands were placed on the chest holding a blue ring. A urethrogram was performed to help visualize the apex of the prostate as there was no magnetic resonance imaging (MRI) study to fuse with the planning CT. Once the patient was immobilized properly, a CT scan of the abdomen and pelvis using 0.3 cm axial slices was performed to obtain a treatment planning data set. The radiation oncologist was called to the simulator to draw the prostate gland. The isocenter was placed in the center of the target volume drawn by the radiation oncologist and reference marks were put on the patient using the LAP laser system in the CT/Sim room (Figure 2). Anatomical Contouring: The CT data set was exported to the Varian Eclipse 11.0 treatment planning system (TPS). The medical dosimetrist contoured the left and right femoral heads, pubic symphysis, bladder, and rectum. A structure that included the bladder minus the PTV plus an additional 2 mm margin and a structure that included the rectum minus the PTV plus an additional 2 mm margin were created for planning purposes only. The radiation oncologist contoured the prostate during the CT/Sim. All of the contours were then reviewed and subsequently approved by the radiation oncologist. Beam Isocenter / Arrangement: A Varian TrueBeam STX was used to plan this patient. The medical dosimetrist placed the beam isocenter in the geometrical center of the prostate (Figures 3-9). The VMAT plan consisted of 2 full arcs: the first arc rotated clockwise from 181.0 degrees to 179.0 degrees in the Varian International Electrotechnical (IEC) 61217 scale and the second arc rotated counter-clockwise from 179.0 degrees to 181.0 degrees. The collimator angle for the first arc was set at 30.0 degrees (Figure 8). The collimator angle for the second arc was set at 330.0 degrees (Figure 9). The couch angle was set at 0.0 degrees. The energy used for each arc was 6 megavolts (MV). Once the treatment objectives were entered into the TPS, the field sizes and multileaf collimator (MLC) positions were automatically set to deliver the optimal target coverage, while sparing the OR and the normal tissue. The monitor units (MU) for the first and second arc fields were 297 and 334, respectively. Treatment Planning: Treatment planning was performed using Eclipse 11.0. The radiation oncologist outlined the treatment prescription and the dose constraints to the OR. The patient received a total of 7740 cGy in 43 fractions at 180 cGy per fraction. The objectives for the target were a maximum and minimum dose, which corresponded to the treatment prescription. The goal was to achieve 95% coverage of the target volume with 100% of the prescribed dose. The

objectives for the bladder were a maximum volume of 15% to receive 6500 cGy and a maximum volume of 40% to receive 4000 cGy. The objectives for the rectum were a maximum volume of 15% to receive 6500 cGy and a maximum volume of 35% to receive 4000 cGy. After several iterations, the TPS achieved an acceptable dose distribution, which included sufficient coverage of the target while maintaining acceptable doses to the OR (Figures 5-7, 10). The plan was designed for treatment on a Varian TrueBeam STX with 120 leaf high-definition MLC (HDMLC). The energy used for both arcs was 6 MV. The maximum dose rate of 600 MU per minute was chosen. The angular resolution value was set at 5 degrees. The plan was normalized to 100% at the primary reference point after being reviewed and approved by the radiation oncologist. Quality Assurance/Physics Check: A quality assurance (QA) plan was delivered to a Sun Nuclear ArcCHECK phantom as well as a Sun Nuclear MapPhan device and subsequently evaluated by Sun Nuclear's SNC Patient software. The measured plan was then compared with the expected plan that was exported by the Eclipse TPS and was within tolerance. The treatment plan and QA measurements were then reviewed by the radiation oncologist and a medical physicist as a final check before treatment began. Conclusion: According to the American Cancer Society, there will be an estimated 233,000 new cases of prostate cancer in 2014.5 They also estimate that there will be 29,480 deaths related to prostate cancer, which is second only to lung and bronchus cancers.5 Although prostate cancer is very common, it can be well controlled with high doses of radiation. Before the introduction of IMRT, 3-D conformal therapy was able to successfully deliver a high dose of radiation to the target but fell short in limiting the doses to the OR. Intensity-modulated radiation therapy delivered utilizing the VMAT technique has been able to deliver high doses to the target, limit the doses to the OR, and reduce the total treatment time. There were several challenges with this case such as reproducibility of bladder, rectal filling, and finding the right optimization objectives. The planning structures created by subtracting the PTV plus a margin assisted in overcoming the challenges of delivering the prescribed dose to the target while minimizing the dose to the normal structures. Overall, the VMAT technique was an excellent option for achieving the planned objectives.

References 1. Sveistrup J, Rosenschold P, Deasy J, Hun Oh J et al. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Radiat Oncol. 2014; 9(1):44. doi:10.1186/1748-717X-9-44 2. Kopp R, Duff M, Catalfamo F, Shah D, Rajecki M, Ahmad K. VMAT vs. 7-field IMRT: Assessing the dosimetric parameters of prostate cancer treatment with a 292-patient sample. Med Dosim. 2011;(36):365-372. doi:10.1016/j.meddos.2010.09.004 3. Palma D, Vollans E, James K, Nakano S et al. Volumetric modulated arc therapy for delivery of prostate radiotherapy: comparison with intensity-modulated radiotherapy and three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72(4):996-1001. doi:10.1016/j.ijrobp.2008.02.047 4. Quan E, Xiaoqiang L, Yupeng L, Xiaochun W et al. A comprehensive comparison of IMRT and VMAT plan quality for prostate cancer treatment. Int J Radiat Oncol Biol Phys. 2012;83(4):1169-1178. doi:10.1016/j.ijrobp.2011.09.015 5. American Cancer Society. Cancer Facts and Figures 2014. Atlanta: American Cancer Society; 2014.

Figures

Figure 1. Image of leg cradle system used. Image courtesy of http://www.civco.com/ro/products/Vac-Lok-Positioning-Cushions.htm.

Figure 2. LAP laser system in the CT/Sim. Image courtesy of www.lap-laser.com.

Figure 3. Anterior-Posterior (AP) Beams Eye View of Treatment Isocenter

Figure 4. Right Lateral Beams Eye View of Treatment Isocenter

Figure 5. Axial view of treatment isocenter. Green isodose line is 100%, blue isodose is 98%, and purple isodose line is 50%.

Figure 6. Coronal view of treatment isocenter. Green isodose line is 100%, blue isodose is 98%, and purple isodose line is 50%.

Figure 7. Sagittal view of treatment isocenter. Green isodose line is 100%, blue isodose is 98%, and purple isodose line is 50%.

Figure 8. Beams Eye View of the first arc field.

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Figure 9. Beams Eye View of the second arc Field.

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Figure 10. Dose Volume Histogram (DVH).