1 Dustin Melancon April Case Study April 23, 2013 Stereotactic Body Radiation Therapy for Squamous Cell

Lung Cancer History of Present Illness: The patient, PF, is a 67-year-old female with stage T1N0 squamous cell carcinoma of the left upper lobe. She was originally treated in 2008 for T2N0 small cell lung cancer. Follow-up tests showed a new left upper lung (LUL) lesion. Both computed tomography (CT) and positron emission tomography (PET) scans showed a left upper lobe lesion more superior than in the previously irradiated small cell lung cancer. Her biopsy was positive for a different histology, squamous cell carcinoma. Past Medical History: The patient has a history of chronic bronchitis. She is allergic to aspirin. A left hilar biopsy of a 3.5 centimeter (cm) mass in 2008 revealed stage T2N0M0 small cell lung cancer. She received chemotherapy with three-dimensional (3D) conformal radiotherapy. Her lung treatment was 5,940 centigray (cGy) in 33 fractions at 180 cGy per fraction with two oblique 6 megavoltage (MV) beams. PF also received prophylactic cranial irradiation with equally weighted right and left lateral 4 MV beams. The whole brain plan included lateral opposed fields with a 5-degree posterior tilt to avoid the eyes. A dose of 3,600 cGy in 20 fractions was given at 180 cGy per fraction. As of September 2011, she states having short-term memory loss, which is likely a late effect of her previous radiation treatment. She continues to visit her physician annually with CT scans of the chest to monitor for any changes. Social History: PF has a smoking history. Her paternal aunt had stomach cancer. Medications: The patient uses the following medications: Multivitamin, Evista, Glucophage, Neurontin, Nexium, Norvasc, Toprol XL, Toviaz, and Vytorin. Diagnostic Imaging: MRI of brain with and without contrast was performed in November 2012 due to history of small cell lung cancer. No mass or abnormal enhancement concerning for metastatic disease was observed. The extensive, diffuse white matter hyperintensities are likely related to radiation change. Also, a CT scan of the patients head was performed without contrast and showed no significant changes. Her lung CT showed irregular nodular opacity in the left mid lung. The patient also received a PET/CT)scan in November 2012 that showed a left upper lobe lesion more superior to the previously irradiated small cell lung cancer. Later, a CTguided lung biopsy confirmed the left upper lung lesion to be squamous cell carcinoma.

2 A four-dimensional (4D) CT simulation scan was performed in February 2013. It consisted of 3D CT data sets that assessed motion of the tumor during the respiratory cycle. A box with infrared reflectors was placed on the patients surface. The boxs motion during each respiratory cycle was captured with an infrared camera. The CT simulation scan was fused with the PET/CT scan. Radiation Oncologist Recommendations: The radiation oncologist considered stereotactic body radiation therapy (SBRT) with 5000 cGy. He considered treating with 500 cGy per day in either 10 fractions if there was significant overlap between the former plan and the new target or 5 fractions if there was no significant overlap (Figures 1-3). After reviewing the patients previous radiation therapy records, the radiation oncologist felt that SBRT could be delivered safely to the new lesion. The radiation oncologist planned 5000 cGy to be delivered in 5 fractions of 1000 cGy with 3 fractions per week. The radiation oncologist discussed the benefits of treatment with PF and what she should expect from her treatment. The radiation oncologist explained that possible treatment side effects include rib fracture, chronic nerve pain, more breathing problems, hemoptysis, and a bronchopulmonary fistula that would require a chest tube. The patient understood the risks, benefits, and side effects. PS signed the informed consent form for SBRT. The Plan (Prescription): The patient will be treated with SBRT in the left upper lung with respiratory gating and cone beam CT. The prescription is for 5000 cGy to be delivered in 5 fractions of 1000 cGy with 3 fractions per week. The radiation oncologist intends to use the Varian TrueBeam accelerator with RapidArc 10 MV beams in flattening filter free (FFF) mode to deliver 100% of the dose to 95% of the target volume (Figure 4). Patient Setup/Immobilization: The patient was head-first and supine in a full body Vac-Lok immobilization device. The patients arms were at her sides and her legs were straight. A wing board was used to raise her arms above her head and out of the treatment field. On treatment days, the patient was positioned according to skin marks and setup lasers. She was then vacuumsealed in the full body Vac-Lok bag with plastic wrap to reduce motion. A box with infrared reflectors was placed on the patients surface. The box was tracked with an infrared camera for respiratory gating in Varians Real-time Position Management system (Figure 5). Cone-beam CT was also used to more accurately align structures. A cone-beam CT acquires x-ray tomography using a flat panel radiation detector on the linear accelerator. The equipment rotates

3 around the patient and images are acquired at multiple angles. These images are reconstructed in three dimensions so the anatomy can be seen in transverse, sagittal, and coronal planes. An algorithm is used to reconstruct the volumetric images so we can localize soft tissue organs just prior to treatment.1 Anatomical Contouring: After completion of the four-dimensional (4D) CT simulation scan, the CT data set was transferred into Varian Eclipse 10.0 treatment planning system (TPS). The radiation oncologist and his attending physician determined the treatment volume. They first identified the disease in the LUL, drew an isocenter and the gross tumor volume (GTV). Next, they drew the clinical target volume (CTV) and a planning target volume (PTV) for the treatment area. The radiation oncologist contoured the aorta and chest wall. The medical dosimetrist contoured the esophagus, trachea, spinal cord, and the lungs. The radiation oncologist later reviewed and approved these contours. The medical dosimetrist was sent an electronic prescription objective to begin planning. Beam Isocenter/Arrangement: A TrueBeam linear accelerator with 10 MV beams in FFF mode was used for treatment. Two stereotactic arc beams were planned at 100 cm source to axis distance (SAD) with 2400 monitor units/minute (MU/min). The first arc had the collimator at 30 degrees, started at 181 degrees, and ended at 179 degrees. The second arc had the collimator at 330 degrees, started at 179 degrees, and ended at 181 (Figure 4). Treatment Planning: Varian Eclipse 10.0 was the TPS used to complete the inverse treatment plan. The arc therapy technique utilizes multileaf collimator (MLC) blocking and intensitymodulated radiation therapy (IMRT). RapidArc allows the gantry to rotate 360 degrees around the patient while the leaves are moving.2 The plan was to deliver 100% dose to 95% of the target volume. This was done based on clinical experience and published data. The dosimetrist used the arc geometry tool for optimal arc placement. This tool considers the linear accelerators parameters as well as the tumors size and location. Next, the objective goals were entered in the plans optimization window according to the physicians objectives and the dose constraint sheet; which contains maximum doses and dose volume limits for critical structures. The target and some of the critical structures were dose volume based, which specifies a fractional volume that can receive certain doses. By defining the desired objectives, the computer could calculate the beam weights, intensity

4 modulation, and dynamic MLC motions to produce the requested dose distribution. After plan optimization, the leaf sequence was generated and the dose distribution was calculated. Two arc beams in FFF mode were used with 10 MV photons and a dose rate of 2400 monitor units per minute (MU/min). When adequate prescription dose coverage was achieved in the target, the medical dosimetrist reviewed the organs at risk (OR), the dose volume histogram (DVH), and the isodose lines (Figures 6-7). The OR on the DVH reflected a maximum spinal cord dose of 636.6 cGy. The mean doses included the PTV with 5301.2 cGy, left lung with 786.0 cGy, right lung with 150.8 cGy, and the spinal cord with 344.0 cGy (Figure 7). The dosimetrist reviewed the plan by examining the dose distribution, tolerance doses, and DVH data. The physician later reviewed the plan and approved it for treatment. Quality Assurance/Physics Check: The SBRT plans quality assurance (QA) check was performed along with Real-time Position Management, which is Varians respiratory gating system. The IMRT QA device, Delta4, captures the dose in the cross-section of the beam. Delta4 uses the patient's structures when it compares the measured and the calculated phantom dose. Deviations are shown in figures and a DVH (Figures 8-10). A medical physicist said a correlating calculation point in both the phantom and the measurement device must be within 3% at our facility. A physicist performed the final check by reviewing the plan before treatment began. Conclusion: It was important to treat the target accurately as possible since the patient was previously treated with 3D conformal therapy for her former small cell lung cancer. Patient immobilization is critical in IMRT because of sharper dose gradients, which is why we see more complex immobilization with our SBRT lung patients. We aimed to accurately treat the PTV while sparing OR. Many SBRT approaches today rely on image-guidance, using either planar or volumetric-based imaging techniques. Image guidance grants us the ability to reduce margins, decrease the normal tissue toxicity, and increase dose acceleration.2 For these reasons, this case used respiratory gating and cone-beam CT. Treatment time can be longer with these techniques. Respiratory gating only allows dose to be delivered at certain parts of the respiratory phase. On the other hand, using RapidArc and FFF mode can significantly reduce the treatment time. This was possible in my case because a larger proportion of radiation dose was delivered at a higher rate when the beam was on. This can also reduce the chance of patient motion during treatment and improve their comfort.3

5 The medical dosimetrist experienced challenges during treatment planning. One challenge was to determine the correct parameters so the arcs could provide adequate coverage of the PTV. Another challenge was determining the best dose constraints. I think this was a really interesting case because SBRT allows us to deliver higher, more accurate doses with greater sparing of normal tissues. Its also interesting because I've never heard of small cell lung cancer patients surviving five years then returning with a new histology.

6 Figures

Figure 1. Lung treatment plan with DVH from previous small cell lung cancer.

Figure 2. Lung treatment plan from previous small cell lung cancer.

Figure 3. Whole brain treatment plan from previous small cell lung cancer.

Figure 4. Treatment plan report.

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Figure 5. 4D CT simulation scan.

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Figure 6. Lung plan with the viewing plane intersection at the PTV.

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Figure 7. DVH for the SBRT plan.

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Figure 8. Dose QA for SBRT plan.

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Figure 9. Dose QA for SBRT plan.

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Figure 10. Dose QA for SBRT plan.

16 References 1. Khan FM. The Physics of Radiation Therapy. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2010. 2. Khan FM, Gerbi BJ. Treatment Planning in Radiation Oncology. 3rd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2012. 3. Ting J. Commissioning of Varian TrueBeam with Flattening Filter Free - FFF Design. AAPM Annual Meeting Online Submission Web site. http://amos3.aapm.org/abstracts/pdf/68-19886-230349-89966.pdf. Accessed April 23, 2013.