1 Ashley Pyfferoen Clinical Practicum II June 5, 2013 Intensity-Modulated Radiation Therapy (IMRT) for Treatment of Pancreatic Adenocarcinoma History

of Present Illness: JI is a 75 year-old female who presented to her primary physician with complaints of debilitating lower back pain and loss of appetite over the previous 2 weeks. After further evaluation, the patient underwent a computed tomography (CT) scan that revealed a 3.5 centimeter (cm) lesion located on the pancreatic head that appeared to have mixed cystic and solid characteristics. The lesion included benign and malignant entities and a serous neoplasm. There was also suspicion of common hepatic artery encasement and a positive 2.5 cm adjacent portacaval lymph node. After the results were obtained, the patient was transferred to a larger clinic to undergo treatment. Upon arrival, the patient underwent a Magnetic Resonance Cholangiopancreatography (MRCP) to further investigate the pancreatic lesion. The results indicated diffuse small cystic changes in the head of the pancreas but were inconclusive regarding a malignant mass. Because of the cystic position, the lesion was not amenable to fine needle aspiration and the patient was discharged with improving symptoms. Approximately 2 weeks later, the patient reported to her primary care physician that symptoms had returned more severe. A repeat CT indicated an increase in the size of unciate process lesions and a 2.8 cm x 2 cm lesion that tracked posterior to the superior mesenteric vein (SMV) and portal confluence. An endoscopic ultrasound (EUS) was performed in early May of 2013 that revealed Stage IIB pancreatic adenocarcinoma. The patient also underwent a chest CT that was negative for any metastases. The patient was again transferred to a larger local clinic to pursue treatment. The patient met with a surgeon to determine eligibility for a pancreaticoduodnectomy. Because of tumor abutment to the SMV, celiac axis, and possible involvement of the common hepatic artery; the patient was a borderline resectable candidate. The surgeon recommended neoadjuvant chemoradiation to improve the possibility of surgery in the future. JI met with a radiation oncologist in late May of 2013 to discuss a course of radiotherapy for her pancreatic cancer. After a thorough discussion of the risks, benefits, and alternatives to a course of neoadjuvant radiotherapy, the patient chose to proceed with radiation treatments.

2 Past Medical History: The patient has a past medical history of hypertension, gastroesophageal reflux disease, chronic kidney disease, overactive bladder and restless leg syndrome. The patient has also undergone several surgical procedures including a total abdominal hysterectomy with bilateral salpingoophorectomy, tonsillectomy and total right hip arthroplasty. Social History: JI is married and a retired office assistant. She denies tobacco use and consumes alcohol approximately once per week. The patient indicated her paternal grandfather died from pancreatic cancer, however, she reported no other close family members have a history of cancer. Medications: The patient is currently taking Norvasc, asprin, Hydrocodone, Zestril, Nitroquick, Prilosec, Zofran, Miralax and Prochlorperazine. Diagnostic Imaging: The patient underwent a CT scan in early April of 2013 after complaints of appetite loss and lower back pain. The scan revealed a 3.5 cm pancreatic head lesion which appeared to have a mixed cystic and solid appearance. A follow-up MRCP was performed to further delineate the pancreatic lesion and provided inconclusive results. In early May, another CT was ordered and determined an increase in size of the unciate process and a 2.8 cm by 2 cm lesion that tracked posterior to the SMV and portal confluence. An EUS was performed and revealed Stage IIB pancreatic adenocarcinoma. Radiation Oncologist Recommendations: The radiation oncologist reviewed the information documented by the surgeon and medical oncologist. After a long discussion with JI, he decided to proceed with external beam radiation therapy to the pancreas. The radiation oncologist elected to treat the lesion using a 5-field IMRT technique. The use of IMRT to treat pancreatic lesions is appreciated in radiation oncology because of the proximity of critical structures such as the kidneys, spinal cord and liver.1 The Plan (prescription): The radiation oncologists plan to treat the pancreas consisted of a 5field IMRT plan using 6 Megavoltage (MV) energy. The pancreas was prescribed to 5040 centigray (cGy) at 180 cGy per fraction for 28 fractions. Because the goal of the entire treatment regimen was curative, the radiation oncologist elected to treat the mass aggressively for the best possible outcome for the patient heading into surgical evaluation. Patient Setup/Immobilization: In May 2013, the patient presented for a CT simulation scan in the radiation oncology department. She was placed in the supine position head first into the scanner. A CIVCO wing board was placed under the patient to remove her arms from the fields

3 and maintain immobilization (Figure 1). A Vac-Loc was placed on top of wing board and conformed to the patients anatomical contour to aid in immobilization (Figure 2). A head and neck rest was secured to the table for patient comfort and a cushion was placed under her knees for lumbar back support (Figure 2). BBs were placed anteriorly and laterally (left and right) on the patients skin to define a reference point for treatment planning. Exac-Trac imaging was used to aid in daily reproducibility and immobilization. Anatomical Contouring: In conclusion of the CT simulation, the axial images were uploaded in the Philips Pinnacle3 8.0 radiation treatment planning system (TPS). The radiation oncologist contoured the gross tumor volume (GTV), clinical target volume (CTV) and planning target volume (PTV) to ensure that the disease was completely encompassed in the treatment field. The medical dosimetrist contoured organs at risk (OR) including left lung, right lung, spinal cord, stomach, liver, left kidney, right kidney, small bowel and large bowel. The medical dosimetrist also contoured the contrast located in the patients stomach and small bowel and administered a density of soft tissue to ensure the contrast would not influence the plan. The radiation oncologist reviewed these OR structures and made necessary adjustments. The medical dosimetrist was then given the prescription of the plan to proceed. Beam Isocenter/Arrangement: The patient was treated on a Varian Clinac 21EX machine. The medical dosimetrist placed the isocenter centrally within the PTV contour to ensure proper dose coverage (Figures 3-5). Because of the uniform shape and size of the PTV, 5 coplanar photon beams were arranged at gantry angles of 236 degrees (), 331, 50, 124, 180 and set to 6MV photon energy. No collimator or couch rotation was necessary. The field size apertures were set automatically by the TPS during configuration to determine the best dose distribution (Figure 6). The medical dosimetrist inserted the prescription and proceeded to planning. Treatment Planning: Because the surgeon thought JI would be a good candidate for surgery with an adequate response from chemotherapy and radiation therapy, the goal of this treatment regime was curative. However, with the proximity of high dose intolerant structures, the radiation oncologist was cautious while determining the best approach to the patients treatment. The PTV objectives instructed by the radiation oncologist were entered in the TPS and included constraints for uniform dose, maximum doses and minimum doses. In addition, several dose constraints were given for OR as well and included: the spinal cord was to be less than 4500 cGy, the right and left kidneys were to have a mean dose less than 1800 cGy and the volume

4 receiving 1800 cGy was to be less than 30%, the small bowel and stomach were not allowed to receive a dose over 5500 cGy and 25%-30% of the volumes could not receive a dose over 4500 cGy, and the mean dose of the liver could not exceed 2500 cGy. While meeting each of these constraints was important, the radiation oncologist indicated that the most important objectives were the spinal cord and kidneys. If proper precautions are not taken to protect the spinal cord, chronic progressive radiation myopathy can develop and significantly decrease the patients quality of life.2 A 1.5 cm uniform structure was created surrounding the PTV and given an objective to ensure the dose decreased quickly outside the PTV before reaching other tissues. A normal tissue objective was also created to control dose outside of the PTV. The TPS used the direct machine parameter optimization (DMPO) feature with 55 segments to create a suitable plan based on the given constraints. After the dosimetrist was satisfied with the PTV dose coverage, she reviewed the dose volume histogram (DVH) to evaluate the OR (Figure 7). The OR displayed by the DVH indicated that the maximum spinal cord dose was 4312 cGy, the right and left kidneys received a mean dose of 4960 cGy and 2945 cGy respectively (Figure 8-9). Additionally, the mean for the left kidney was 960 cGy and mean for the right kidney was 1650 cGy (Figure 8-9). The small intestine and stomach received maximum doses of 5209 cGy and 5130 cGy respectively and 7% of the small bowel volume and 3% of the stomach volume received 4500 cGy (Figure 8-9). Finally, the liver received a mean dose of 570 cGy (Figure 8-9). With so many dose constraints, the dosimetrist found it difficult to analyze, however, each of these doses were within the tolerance indicated by the radiation oncologist. After all the constraints had been met, the dosimetrist attempted to achieve better conformity around the PTV which proved to be more difficult than meeting the constraints. The radiation oncologist reviewed the plan and allocated a normalization of 98.6%. Quality Assurance/Physics Check: To ensure the plan was treatable and to verify monitor units (MU), the physicist transferred the plan to the treatment console and administered the quality assurance (QA) program MapCheck 6.2.3. The physicist treated the plan on the phantom and collected data and measurements. The measured dose grid was compared to the dose grid produced by the TPS and verified an absolute point dose and relative dose fluence. Each of these comparisons were in tolerance (3%) of the TPS calculations. The MUs were also within tolerance (5%) based on department protocol. The physicist also verified that the prescription

5 and treatment fields were correct, the digitally reconstructed radiographs (DRRs) were associated properly and the patients treatment schedule was accurate. Conclusion: The 5-field IMRT plan presented the medical dosimetrist a few difficulties. First, it was difficult to achieve conformity outside of the PTV. While there were no areas of the PTV receiving 105% of the dose, the TPS struggled to conform the 100% isodose line perfectly around the delineated PTV. Several optimizations were required before the dose conformity improved within standards. Also, there were several structures with multiple constraints to account for in the optimization. While achieving the objectives instructed by the radiation oncologist didnt require several optimizations, it was troublesome to analyze. Overall, I am very pleased with this plan. I was able to achieve the dose conformity I was looking for while achieving all of the constraints for my first IMRT plan. This plan had a significant impact in my planning experience. I was able to create a great plan based on the radiation oncologists parameters, but I think it is important to realize that meeting the constraints will not always be as easy. Considering this is my first IMRT plan, I am excited but cautious for my next experience.

6 Figures

Figure 1. Patient is immobilized on a CIVCO wing board.

Figure 2. A cushion was used for patient comfort and a Vac-loc was used for immobilization.

Figure 3. Isocenter placement in axial view.

Figure 4. Isocenter placement in sagittal view.

Figure 5. Isocenter placement in coronal view.

Figure 6. IMRT field sizes determined by TPS.

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Figure 7. Display of isodose curves in several axial slices. The red isodose line is indicative of prescription dose.

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Figure 8. Dose Volume Histogram (DVH).

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Figure 9. Dose Volume Histogram (DVH).

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References

1. Milano M, Chmura S, Garofalo M, et al. Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome. Int J Radiat Oncol Bio Phys. 2004;59(2):445-453. 2. Gocheva, L. Radiation tolerance of the spinal cord: doctrine, dogmas, data. Arch Oncol. 2000;8(3):131-134.