1 Ashley Pyfferoen Clinical Practicum II July 15, 2013 Intensity Modulated Radiation Therapy (IMRT) for treatment of Non-small

Cell Squamous Carcinoma of the Right Lung History of Present Illness: Patient TB is a 54 year-old man who presented to his primary care provider in June of 2013 after being bitten by a tick. A chest X-ray was ordered and revealed an abnormal mass located in the superior right lung and apex. A chest computed tomography (CT) scan was ordered and revealed a 6 centimeter (cm) soft-tissue mass in the right upper lobe, abutting and invading the mediastinum with mediastinal adenopathy. The patient was referred to pulmonology for further evaluation. To further delineate the superior lung mass and mediastinal node involvement, biopsies of each site were ordered. In June 2013, the patient had an endobronchial ultrasound (EBUS) guided fine needle aspiration biopsy of the mediastinal lymph nodes and a transbronchial biopsy of the right lung nodules. A final pathology report revealed metastatic poorly differentiated squamous cell carcinoma in the mediastinum. The right upper lobe specimen was negative for malignancy; however, moderately differentiated keratinizing malignant epithelium was detected. A Positron Emission Tomography (PET)-CT scan was ordered and confirmed previous suspicions of lesion size and mediastinal involvement with significant F-18 fluorodeoxyglucose (FDG) uptake. A pulmonary function test (PFT) was completed in early to mid-June of 2013 to determine the patients eligibility for surgery. He performed well on the PFT, however, due to tumor size and spread he was not a good candidate for surgical removal. The patient met with the radiation oncologist to discuss a round of radiotherapy to the right upper lobe. The radiation oncologist recommended TB have a Magnetic Resonance Imaging (MRI) scan to investigate the possibility for brain metastasis. The scan was conducted soon thereafter and was negative for metastasis. TB met with the radiation oncologist for a follow-up appointment to discuss treatment options. After a thorough discussion of the risks, benefits, and alternatives to radiation therapy, the patient chose to proceed with radiation treatments to manage his disease. Past Medical History: TB has a past medical history of debilitating chronic back pain. Past surgical histories include back fusion surgery, hernia surgery and arthroscopic knee surgery.

2 Social History: The patient is divorced and unemployed. He receives disability benefits due to his history of chronic back difficulties. TB denies the use alcohol or drugs. He indicates he is an everyday smoker and has a 40-year smoking history. He is currently trying to stop smoking and only smokes 1-2 cigarettes per day. However, he admits to smoking 1-2 packs of cigarettes per day for a majority of his smoking history. He indicates there is no family history of cancer. Medications: TB is currently taking Cyclobenzaprine, Dexamethasone, Duloxetine, Fentanyl, Hydrocodone, Lorazepam and a multivitamin tablet. Diagnostic Imaging: After an irregular mass was detected, the patient received a diagnostic chest CT that revealed a 6 cm lesion located in the superior lobe of the right lung and extended to the superior apex and mediastinum. A subsequent PET-CT scan was ordered to determine if there were any local or distant metastases. The mediastinum and upper right lung lesions were positive for FDG uptake and the scans determined that TBs disease was locally advanced to the mediastinal nodes. A brain MRI was ordered prior to treatment recommendations and was negative for brain metastases. After diagnostic imaging was complete, TB was diagnosed with T4 (Stage 4 primary tumor), N2 (Stage 2 regional lymph nodes), MX (metastasis could not be evaluated) disease. Radiation Oncologist Recommendations: After reviewing the information, the radiation oncologist recommended that TB proceed with external beam radiation therapy treatments. The radiation oncologist elected to treat the superior lung lesion with an IMRT technique. This treatment technique has shown to have significant benefits for these types of patients.1 A study by Sura et al., compared the 3-dimensional (3D) conformal treatment technique with IMRT for the treatment of non-small cell lung cancer demonstrated that IMRT was able to deliver the prescribed dose to the tumor while limiting dose to critical structures.1 The research indicated the IMRT plan had a significantly lower mean lung dose (MLD), lower lung volume receiving 20 Gray (Gy) and lower lung volume receiving 25 Gy then the 3D plan.1 In addition, the benefit was greatest for those patients with medium to large sized non-small cell lung cancer.1 With this research in mind, TB was an ideal candidate for this type of treatment. The Plan (prescription): The radiation oncologists plan to treat the superior lung consisted of an IMRT plan using 6 Megavoltage (MV) energy. The lung lesion was prescribed to a dose of 6000 centigray (cGy) at 200 cGy per fraction for 30 fractions. There was no boost plan for this patient. Because the goal of radiation therapy was local control, the radiation oncologist elected

3 to treat the mass cautiously to avoid causing side effects that could compromise the patients quality of life. Patient Setup/Immobilization: The patient presented to the radiation oncology department in mid-June of 2013 for a 4-dimensional (4D) CT simulation scan. He was placed in the supine position head first into the scanner. A CIVCO wing board was placed under the patient to remove his arms from the fields and maintain immobilization (Figure 1). A Vac-Loc was placed on top of the 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 his knees for lumbar back support (Figure 2). Radiopaque reference markers 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: At the conclusion of the CT simulation, the images were uploaded to the General Electric (GE) 4D workstation. The physicist uploaded the images and averaged the CT slices to create a treatment planning CT. The averaged CT set was sent to the Philips Pinnacle3 8.0 radiation treatment planning system (TPS). The radiation oncologist used the PET and CT scans to contour the internal target volume (ITV) and planning target volume (PTV) to ensure that the lesions were completely encompassed in the treatment field. The medical dosimetrist contoured the organs at risk (OR) including the brachial plexus, left lung, right lung, heart, spinal cord, and esophagus. The radiation oncologist reviewed these OR structures and made necessary adjustments. The medical dosimetrist was then given the prescription of the plan to proceed. The radiation oncologist noted special attention to the brachial plexus dose. The most respected literature on the brachial plexus limitations in radiation therapy indicate that 60 Gy should be the maximum dose allowable, however, information on this dose appears only sporadically.2 Due to the proximity and overlap of the PTV with the brachial plexus, it is essential that the brachial plexus remain at or under prescription dose to eliminate the possibility of radiation-induced brachial plexopathy.3 With this information in mind, the medical dosimetrist proceeded with IMRT treatment planning. Beam Isocenter/Arrangement: The patient was treated on a Varian Clinac 21EX machine. The medical dosimetrist placed the isocenter within tissue that was contoured in the PTV volume. The isocenter was located approximately 1.1 cm from the lung interface to ensure enough dose

4 buildup before entering the lung tissue (Figures 3-5). Seven coplanar beams were placed around the isocenter at 205, 240, 320, 10, 52, 125 and 160 and set to 6 MV 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. The medical dosimetrist inserted the prescription and proceeded to planning. Treatment Planning: Because the goal of this treatment regimen was local control, the dose criteria was more relaxed than typical lung treatments. Due to the proximity of the spinal cord and brachial plexus, the physician did not specify a particular dose to the tumor. He requested that the minimum dose be greater than 45 Gy, however, he also noted to achieve the best coverage possible while meeting the brachial plexus and spinal cord constraints. The physician also listed OR constraints that included the right and left lung, esophagus, spinal cord and brachial plexus. The brachial plexus and spinal cord were of most concern with maximum doses of 6000 cGy and 4500 cGy respectively. The right and left lungs were not allowed to receive more than 2000 cGy to 25% of the contoured volume and 500 cGy to 55% of the contoured volume. The mean dose to the total lung contour was not to exceed 1750 cGy and the mean esophagus dose was to be less than 2500 cGy. Finally, the mean heart dose could not exceed 3000 cGy. Prior to beginning the plan, the medical dosimetrist expanded the PTV volume 1.5 cm to ensure the dose decreased quickly outside the PTV before reaching other tissues. The spinal cord contour was also expanded 5 millimeters (mm) for optimization and margin purposes. As denoted in Figure 6, the brachial plexus contour overlapped the contoured PTV in several slices. The medical dosimetrist subtracted the 2 volumes to create a structure for dose optimization in the overlap (Figure 7). Because the brachial plexus was of higher priority, it was imperative that the TPS deliver less than or equal to the prescription dose to the overlapped area. The medical dosimetrist then proceeded to the direct machine parameter optimization (DMPO) feature to begin IMRT planning. The program used 75 segments to create a suitable plan based on the given constraints. The medical dosimetrist entered the constraints for the PTV and OR to achieve the desired objectives. After initial iterations, the TPS was having difficulty delivering 100% of the dose to the distal and inferior aspects of the PTV. The medical dosimetrist altered the constraints and optimized the plan again. After several more iterations, the TPS was able to deliver sufficient dose to the distal and inferior aspects of the PTV (Figure 10-12). The TPS was also able to give sufficient margin from the prescription dose around the brachial plexus (Figures

5 8-9). Although the medical dosimetrist was not given a PTV constraint, she was able to conform the 5700 cGy isodose curve around the entire PTV, underdosing the brachial plexus. When the medical dosimetrist was satisfied with the dose distribution, the dose volume histogram (DVH) was analyzed to ensure the dose constraints were met (Figure 13-14). The DVH indicated that only 89.5% of the PTV was receiving 6000 cGy (Figure 13). The medical dosimetrist analyzed the areas of the PTV that received less than prescription dose. All of the underdosed areas were near the brachial plexus and therefore, acceptable. The DVH confirmed the brachial plexus was receiving a dose of 6001.3 cGy (Figure 13). The radiation oncologist reviewed the structure and accepted the overdose of 1.3 cGy. The spinal cord with 5 mm margin received a maximum dose of 4375 cGy with the actual spinal cord maximum dose at 3957 cGy (Figure 13). The expanded spinal cord volume ensured the spinal cord would receive a dose lower than 4500 cGy. The total lung volume receiving 2000 cGy was observed at 27% (Figure 14). While the radiation oncologist opted for a percentage less than 25%, he accepted 27% due to the size of the tumor inside the lung cavity. The mean lung dose was 1379 cGy and the volume receiving 500 cGy was 46% (Figure 14). The mean esophagus dose was identified at 3447 cGy. The constraint was listed at 2500 cGy (Figure 14). The physician accepted a higher mean dose to the esophagus due to the proximity of the tumor to the structure. Finally, the mean dose to the heart was 431 cGy and well below the dose constraint (Figure 14). The medical dosimetrist encountered the greatest difficulty in controlling the PTV dose around the brachial plexus and adequately covering the PTV with prescription dose in the lung cavity. The medical dosimetrist also found it difficult to deliver dose in the lung interface due to the lack of tissue buildup. Meeting the lung and esophageal constraints also proved to be difficult for the medical dosimetrist and was thoroughly discussed with the radiation oncologist. The physician accepted the plan and normalized to the 96.5% isodose line to ensure proper dose coverage. 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 within tolerance (3%) of the TPS calculations. The MUs were also within tolerance (5%) based on department protocol. The physicist also verified that the prescription

6 and treatment fields were correct, the digitally reconstructed radiographs (DRRs) were associated properly and the patients treatment schedule was accurate. Conclusion: This IMRT plan presented the medical dosimetrist with a few planning difficulties. It was difficult to limit prescription dose to the brachial plexus because of the proximity and overlap. The radiation oncologist and medical dosimetrist had to settle for less than prescription dose near these areas. In addition, the medical dosimetrist found it difficult to obtain suitable dose near the distal and inferior aspects of the PTV because of the air density in the lung volume. However, increasing the priority and normalizing to a lower isodose curve allowed the TPS to create a suitable plan for treatment. The dose constraints were also difficult to attain for this lung case. The lung and esophageal doses were very dependent on tumor size and proximity. Due to his advanced staging and mediastinal involvement, the medical dosimetrist was not surprised that these constraints were not met. The medical dosimetrist discussed these concerns with the radiation oncologist and he accepted the doses. This treatment plan was very similar to other case studies written previously. It is obvious that department protocol uses the brachial plexus as a dose limiting structure. This plan aided in the understanding of constraints and dose limitations of the brachial plexus and will be referred to often.

7 Figures

Figure 1. Patient is immobilized on a CIVCO wing board and his arms were removed from the field.

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. Overlap between brachial plexus and PTV contour (PTV=cyan, Brachial plexus = purple).

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Figure 7. Brachial plexus and PTV overlap delineated (pink) and given separate constraints in IMRT optimization.

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Figure 8. Superior aspect of PTV (cyan) with isodose curves displayed (red = 6000 cGy, yellow = 5700 cGy)

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Figure 9. Superior aspect of PTV (cyan) with isodose curves displayed (red = 6000 cGy, yellow = 5700 cGy).

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Figure 10. Medial aspect of PTV (cyan) with isodose curves displayed (red = 6000 cGy, yellow = 5700 cGy).

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Figure 11. Inferior aspect of PTV (cyan) with isodose curves displayed (red = 6000 cGy, yellow = 5700 cGy).

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Figure 12. Inferior aspect of PTV (cyan) with isodose curves displayed (red = 6000 cGy, yellow = 5700 cGy).

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PTV

ITV

Brachial Plexus

Spinal Cord (dark green)

Spinal Cord + 5mm

Figure 13. DVH display of critical structures and PTV and ITV volumes for evaluation.

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Esophagus

Total Lung

Heart

Figure 14. DVH display of critical structures for evaluation.

18 References 1. Sura S, Gupta V, York E, et al. Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Radiother Oncol. 2008;87(1):17-23. 2. Truong M, Nadgir R, Hirsch A, et al. Brachial plexus contouring with CT and MR imaging in radiation therapy planning for head and neck cancer. Radiographics. 2010;30(4):10951103. 3. Amini A, Yang J, Williamson R, et al. Dose constraints to prevent radiation-induced brachial plexopathy in patients treated for lung cancer. Int J Radiat Oncol Biol Phys. 2012;82(3): 391398.