1 Ashley Pyfferoen Clinical Practicum II June 26, 2013 Intensity Modulated Radiation Therapy (IMRT) Technique to Treat Squamous

Cell Carcinoma of the Right Lung History of Present Illness: Patient BN is a 74 year-old woman who presented to her primary care provider in November of 2012 with several episodes of hemoptysis. A chest Computed Tomography (CT) scan was ordered and revealed a large cavitary mass located in the apical interface of the right lung. The patient was referred to a pulmonologist for further evaluation but declined the recommendation and opted for a 3 month follow-up with repeat imaging. The patient presented for the 3 month follow up appointment and imaging with a new complaint of right shoulder pain. A repeat CT revealed the mass was aggressively growing. A biopsy of the mass was ordered and revealed poorly differentiated squamous cell carcinoma. A diagnostic Positron Emission Tomography (PET) scan was ordered to further delineate the mass. The scan was negative for adenopathy or metastatic disease but confirmed a mass greater than 5 centimeters (cm) with possible upper chest wall and brachial plexus involvement. Magnetic Resonance Imaging (MRI) scans of the brain and shoulder were also ordered to identify any brain metastases and determine the source of her shoulder pain. The brain MRI was negative but the patient was unable to complete the shoulder MRI due to increasing pain. The patient met with a surgeon to discuss options to remove the lesion. A pulmonary function test (PFT) was ordered to determine if BN was a candidate for surgery. The PFT results were poor, therefore, BN was not a good candidate for surgery. In May of 2013, the patient met with the radiation oncologist to discuss a round of radiotherapy to the right upper lobe. After a thorough discussion of the risks, benefits, and alternatives to radiation therapy, the patient chose to proceed with treatments to manage her disease. Past Medical History: The patient has a past medical history of stage 4 chronic kidney disease, anxiety, bipolar disorder, hyperlipidemia, osteoporosis, urinary incontinence due to stress and tobacco abuse. Past surgical procedures include a tonsillectomy and appendectomy. Social History: The patient is divorced with living children and friends whom she relies on for daily activities. She denies any alcohol or drug use. She currently smokes 1 pack of cigarettes per

2 day and has for the last 60 years. The patient indicated that both her mother and father deceased in the 7th decade of life. There was no history of cancer indicated. Medications: The patient is currently taking Diazepam, Hydrocodone and Olanzapine. Diagnostic Imaging: BN underwent a diagnostic chest CT scan in early November 2012 that revealed a lesion located in the apical interface of the right lung. After declining further evaluation, the patient returned 3 months later for a follow-up appointment, imaging and complaints of worsening pain in her right shoulder. A CT scan indicated the lesion significantly increased in size. A PET scan was requested in early May of 2013 to further delineate the lesion and identify possible metastatic spread. The PET scan revealed a 4.0 x 2.4 x 5.8 cm mass involving the right lung apex compatible with primary bronchogenic neoplasm. There was concern for possible chest wall and brachial plexus invasion. The scan also revealed scattered areas of nodular septal thickening involving the right upper lobe indicating lymphangitic tumor spread. No other hypermetabolic adenopathy was identified. An MRI scan was performed just prior to the patient beginning treatments to address BNs worsening shoulder pain and investigate the possibly of brain metastases. The brain MRI was negative for lesions; however, the patient was unable to complete the shoulder MRI due to worsening pain. BN was diagnosed with non-small cell lung cancer with a stage of T4, N0, M0 involving the right superior sulcus. Radiation Oncologist Recommendations: After reviewing the information, the radiation oncologist recommended that BN 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 comparing 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 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, BN 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. Because the goal of radiation therapy was

3 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 mid-May of 2013 for a 4-dimensional (4D) CT simulation scan. 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 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 her 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 Varian Eclipse Version 10.0 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. With the proximity of the tumor to the brachial plexus, he was concerned especially with overdosing the structure. There have been studies outlining the limitations of the brachial plexus in head and neck cancer research, however, little research exists on thoracic patients.2 With this information in mind, the medical dosimetrist proceeded with the plan. 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 1.35 cm from the lung interface to ensure enough dose buildup before entering the lung tissue (Figures 3-5). Five coplanar beams were placed around

4 the isocenter at 197 degrees (), 250, 328, 10, 153 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 (Figure 6). 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 PTV objective instructed by the radiation oncologist requested that 100% of the prescription dose cover 95% of the delineated PTV. The physician noted accepting a lower dose in the area surrounding the brachial plexus to ensure no overdose as noted above. 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 30% of the contoured volume and he noted the esophagus mean was to be less than 3200 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. Finally, the brachial plexus contour was expanded 2 mm to give margin for optimization. As denoted in Figure 7, the 2 mm margin 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 8). 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 sliding window IMRT optimization. The medical dosimetrist entered the constraints for the PTV and OR to achieve the desired objectives. After the initial iterations, the PTV was not receiving any of the prescription dose indicated (Figures 9-10). Several more iterations were performed and overall, the plan was insufficient. Based on these results, the medical dosimetrist opted to use the plan as a base dose plan. She reduced the number of fractions to half of the original prescription (17 fractions) and proceeded to another trial. Figures 9 and 10 demonstrate the TPSs inability to deliver adequate dose to the PTV. In a new trial, the medical dosimetrist selected the previous dose plan (base dose plan) as a starting point to continue the previous optimization. After several iterations, the TPS was able to calculate a suitable PTV dose that met the constraints requested by the physician

5 (Figure 11-17). After more optimizations, the medical dosimetrist was successful in sculpting the 6468 Gy isodose line around the expanded brachial plexus (Figures 11-12). To confirm dose constraints were met, the medical dosimetrist analyzed the dose volume histogram (DVH) (Figure 18). The DVH indicated that only 80% of the PTV was receiving 6600 cGy (Figure 18). The medical dosimetrist confirmed that the physician would accept a lower PTV dose near areas abutting the brachial plexus. The DVH confirmed the brachial plexus was receiving a dose of 6599.5 cGy, the spinal cord received a dose of 4330 cGy and the right and left lungs received mean doses of 1522 cGy and 380 cGy, respectively (Figure 18). In addition to the mean doses, the volume receiving 20 Gy was 24.7% for the right lung and 1.5% for the left lung (Figure 18). Finally, the mean dose of the esophagus was 1379 cGy (Figure 18). 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 radiation oncologist reviewed the plan and accepted the under-dosed PTV near the brachial plexus. The physician normalized the plan to 99.2% 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 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 several difficulties. It was difficult to deliver sufficient dose to the PTV. Because the tumor was located at the lung interface, there was no tissue for the photons to build up and deliver dose to the most posterior portions of the PTV. While optimizing the plan, the medical dosimetrist was able to achieve the dose conformity necessary to reach the plan goal; however, the calculated plan provided a far worse dose distribution then indicated in the optimization window. While the pencil beam algorithm (PBC) expressed that all the constraints had been met in the optimization, the anisotropic analytic algorithm (AAA) was unable to successfully calculate the doses. Secondly,

6 the medical dosimetrist found it difficult to sculpt prescription dose perfectly around the brachial plexus, especially when a majority of the brachial plexus overlapped the delineated PTV. The medical dosimetrist was able to achieve the constraints by entering optimization parameters and weighting them accordingly. As noted previously, the dose limit to the brachial plexus while treating thoracic patient is not well documented and it is important to be mindful of the information that is available and follow guidelines. While the PTV around the brachial plexus was significantly underdosed, the margin accounts for any set-up errors or patient movement during treatment. Overall, the plan was suitable for the patient. The medical dosimetrist was able to attain the parameters specified by the radiation oncologist while considering the highest priority objectives. This plan took a significant amount of time to complete. However, the extra time spent optimizing the plan was an obvious benefit to the patient and significantly impacted my clinical experience. A great deal was learned about base dose plans and will be referred to often.

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.

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Figure 5. Isocenter placement in sagittal view.

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Figure 6. IMRT field size determined by TPS.

Figure 7. Expanded brachial plexus volume (pink) that overlapped PTV (cyan).

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Figure 8. Expanded brachial plexus volume (pink) detracted from PTV volume (cyan). The overlapped area is denoted in blue.

Figure 9. Superior PTV on the base dose plan.

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Figure 10. Inferior PTV on base dose plan.

Figure 11. Isodose distribution around the brachial plexus (red= 6600 cGy, purple= 6468 cGy, yellow=brachial plexus).

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Figure 12. Isodose distribution around the brachial plexus (red= 6600 cGy, purple= 6468 cGy, yellow=brachial plexus).

Figure 13. Isodose distribution around PTV (red=6600 cGy, yellow=brachial plexus).

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Figure 14. Isodose distribution around PTV (red=6600 cGy).

Figure 15. Isodose distribution around PTV (red=6600 cGy).

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Figure 16. Isodose distribution around PTV (red=6600 cGy).

Figure 17. Isodose distribution around PTV (red=6600 cGy).

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PTV (red), CTV (blue), GTV (green)

Brachial Plexus

Rt Lung
Esophagus Spinal cord Total Lung

Heart

Lt Lung

Figure 18. DVH

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. Kong F, Ritter T, Quint D et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs and brachial plexus. Int J Radiat Oncol Biol Phys. 2011;81(5):1442-1457.