1 Ashley Pyfferoen Clinical Practicum III October 21, 2013 IMRT to treat small cell lung cancer located

in the right lung apex History of Present Illness: Patient LH is a 74 year-old male who presented to his primary care physician in late August of 2013 with complaints of worsening back pain. A thoracic spinal x-ray was ordered and revealed a lung mass located in the right superior lung measuring approximately 3 centimeters (cm) in size. Subsequent imaging was ordered to further delineate the lung lesion. A diagnostic thoracic Computed Tomography (CT) scan confirmed the presence and size of the lesion. In addition, substantial hilar and mediastinal adenopathy and a positive supraclavicular lymph node were noted adjacent to the lesion suggesting nodal expansion. The radiologist also noted the presence of an 8 millimeter (mm) lesion located in the inferior portion of the left lung. A Positron Emission Tomography (PET) scan was ordered to confirm the CT results. The superior right lung pulmonary lesion was positive for Fludeoxyglucose (FDG) uptake and suggested malignancy. The supraclavicular and mediastinal regions were also positive for FDG uptake. Upon review of the imaging studies, an endoscopic bronchoscopy was performed to determine the histology of the right lung apex lesion. The bronchoscopy was performed in early September and revealed small cell lung cancer. The left lung lesion was not investigated. Based on these findings, a Magnetic Resonance Imaging (MRI) Scan of the brain was ordered to determine the possibility of brain metastasis. Literature dating back to the 1980s demonstrated that patients with small cell lung cancer have an increased probability of developing brain metastasis.1 More recent research suggested that as many as 50% of patients diagnosed with this disease develop brain metastases sometime in the remainder of their life.1 The MRI was negative for metastases in this case. With this information, the patient was referred to radiation oncology to discuss the possibility of radiation therapy treatments for the lung and mediastinal nodules. After a thorough discussion of the risks, benefits, and alternatives to radiation therapy, the patient chose to proceed with treatments to manage his lung disease. Past Medical History: LH has a past medical history of hypogonadism, diverticulosis, Diabetes mellitus type II, hypertension, hypercholesterolemia, benign prostatic hyperplasia (BPH) and an adenomatous colon polyp. Past surgical history includes rectal polypectomy, excision of basal cell carcinoma, bilateral cataract surgery, appendectomy and carpal tunnel disease.

2 Social History: LH is widowed with living children who assist in his transportation to and from the clinic. The patient admits to a 35-year cigarette smoking history, smoking approximately 2 packs of cigarettes per day. He also indicated his mother deceased from colon cancer; however, no other family history of cancer was reported. Medications: The patient is currently taking acetic acid, asprin, Fenofibrate, Glimepiride, Lisinopril-hydrochlorothiazide, Metformin and Pravastatin. Diagnostic Imaging: In August 2013, LH underwent a thoracic spinal x-ray to determine the source of his recent back pain. The x-ray demonstrated a suspicious 3 cm lesion located in the apex of the right lung. A CT scan confirmed the lesion size and demonstrated significant hilar and mediastinal adenopathy with the addition of an enlarged supraclavicular node. The CT scan also identified the possibility of a metastasis or new primary cancer located in the inferior lobe of the left lung. A PET scan was ordered to determine the extent of involvement. The left and right lung lesions, mediastinal, and supraclavicular nodal regions were positive for FDG uptake. A biopsy of the right lung nodule identified small-cell lung cancer. An MRI was ordered to determine the presence of brain metastases and confirm the most optimal treatment regimen. The MRI was negative for brain metastasis and the patient was diagnosed with T2 (Stage 2 primary tumor), N0 (no nodal involvement indicated), M0 (no metastatic spread indicated) disease. Radiation Oncologist Recommendations: After reviewing the information, the radiation oncologist recommended LH proceed with external beam radiation therapy treatments. The radiation oncologist elected to treat the superior lung lesion with an intensity modulated radiation therapy (IMRT) technique. This treatment technique has shown to have significant benefits for these types of patients.2 Sura et al,2 demonstrated a study comparing the 3-dimensional (3D) conformal treatment technique with IMRT for the treatment of Non-small cell lung cancer (NSCLC). The study demonstrated that IMRT was able to deliver the prescribed dose to the tumor while limiting dose to critical structures. The IMRT plan had a significantly lower mean lung dose (MLD), a lower lung volume receiving 20 Gray (Gy) and a lower lung volume receiving 25 Gy then the 3D plan.2 With this research in mind, LH 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 was prescribed to 6600 centigray (cGy) at 200 cGy per fraction for 33 fractions. There was no boost plan for this patient. Because

3 the goal of radiation therapy was curative, the radiation oncologist elected to treat the mass aggressively for the best possible outcome for the patient. Patient Setup/Immobilization: The patient presented to the radiation oncology department in September 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-Lok 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 axial images were uploaded to the General Electric (GE) 4D workstation, where the physicist averaged the CT slices to create a data set for treatment planning. The physicist sent the averaged CT data set to the Phillips Pinnacle Version 8.0 radiation treatment planning system (TPS). The radiation oncologist used the PET and CT scans to contour 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 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 and the dose constraints of limiting structures to proceed. The physician noted specific instructions to limit dose to the brachial plexus. 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.3 Due to the proximity and overlap of the PTV with the brachial plexus, it is essential that the brachial plexus remain under prescription dose to eliminate the possibility of radiation-induced brachial plexopathy.4 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 the right lung located centrally in the PTV

4 volume (Figures 3-5). Because the central portion of the tumor was not inside a tissue interface, a calculation point was placed inferiorly inside the mediastinum to ensure adequate dose buildup when entering the lung tissue (Figure 6). Five coplanar beams were placed around the isocenter at 220, 345, 25, 145 and 175 and set to 6 MV photon energy. No collimator rotations were necessary. The field size apertures were expanded approximately 1 cm from the PTV interface to achieve the best dose distribution. The medical dosimetrist inserted the prescription and proceeded to planning. Treatment Planning: While the goal of this treatment regimen was curative, the medical dosimetrist was cautious while approaching the plan due the proximity of dose limiting structures. The optimal PTV objective given by the radiation oncologist stated that 100% of the prescription dose covers 95% of the delineated PTV. However, the physician noted accepting a lower dose in the area surrounding the brachial plexus to ensure no overdose. If the optimal PTV objective was not attainable, he noted an acceptable does of 6000 cGy to 95% of the PTV. The physician also listed OR constraints that included the right and left lung, esophagus, spinal cord, heart 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 35% of the contoured volume and required a mean dose of less than 2000 cGy. In addition, he noted the esophagus mean dose was to be less than 3400 cGy. The heart was not allowed to receive more than 6000 cGy to 33% of the contoured volume, 4500 cGy to more than 67% of the contoured volume and 4000 cGy to more than 100% of the contoured volume. 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 mm for optimization and margin purposes. As denoted in Figure 7, 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 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

5 100% of the dose to the inferior aspect of the PTV. The medical dosimetrist altered the constraints and optimized the plan again. After several more iterations, the TPS was able to deliver 6600 cGy to the inferior aspect of the PTV (Figure 10-11). The TPS was also able to give sufficient margin from the prescription dose around the brachial plexus (Figures 8-9). The medical dosimetrist was able to conform the 6270 cGy isodose curve around the 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 12). The DVH indicated that only 87% of the PTV was receiving 6600 cGy (Figure 12). The medical dosimetrist analyzed the areas of the PTV that received less than prescription dose. Although the PTV was not receiving the optimal PTV dose, the secondary PTV constraint was achieved (99% of the PTV received 6000 cGy). All of the underdosed areas were near the brachial plexus and therefore, acceptable. The DVH confirmed the brachial plexus was receiving a dose of 6211 cGy (Figure 12). The radiation oncologist reviewed the structure and accepted the overdose of 211 cGy. The spinal cord with 5 mm margin received a maximum dose of 4595 cGy with the actual spinal cord maximum dose at 4361 cGy (Figure 12). 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 33% and the mean lung dose was 1880 cGy (Figure 12). The mean esophagus dose was identified at 2559 cGy. Finally, all of the heart constraints were exceptionally satisfied. The heart volume receiving 6000 cGy was observed at 2%, the volume receiving 4500 cGy was observed at 4% and the volume receiving 4000 cGy was 5% (Figure 12). 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. The physician accepted the plan and normalized to the 97% 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

6 tolerance (5%) based on department protocol. The physicist also verified that the prescription 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 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. 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.

Figure 2. A cushion was used for patient comfort and a Vaclok 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.

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Figure 6. Placement of calculation point in axial view.

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Figure 7. Overlap between brachial plexus and PTV contour (PTV=red, Brachial plexus = blue).

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Figure 8. Superior aspect of PTV (red) with isodose curves displayed (yellow = 6600 cGy, purple = 6270 cGy).

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Figure 9. Medial aspect of PTV (red) with isodose curves displayed (yellow = 6600 cGy, purple = 6270 cGy).

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Figure 10. Medial aspect of PTV (red) with isodose curves displayed (yellow = 6600 cGy, purple = 6270 cGy).

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Figure 11. Inferior aspect of PTV (red) with isodose curves displayed (yellow = 6600 cGy, purple = 6270 cGy).

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PTV

Esophagus Right Brachial Plexus Spinal Cord Total Lungs

Heart

Figure 12. DVH display of critical structures for evaluation.

17 References 1. Postmus P, Haaxma-Reiche H, Smit E, et al. Treatment of brain metastases of small cell lung cancer: comparing tenoposide with teniposide with whole-brain radiotherapy-a phase III study of the European organization for the research and treatment of cancer lung cancer cooperative group. J of Clin Oncol. 2000;18(19):3400-3408. 2. 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. 3. 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):1095-1103. 4. 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): 391-398.