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1 Amanuel Negussie October Case Study Oct.

15, 2013 VMAT for Tonsillar Cancer History of Present Illness: MN is a 65 year old gentleman with chief complaint of the left tonsil. The patient initially presented with a sore throat, poor appetite, hoarseness, and difficulty swallowing. He also complained of being fatigued, experiencing nausea and muscle cramps often. On head, eyes, ears, nose and throat (HEENT) examination, an ulcerated lesion in the left superior tonsillar pole was detected. There was no neck adenopathy. Biopsy of the left tonsil lesion showed invasive moderately differentiated squamous cell carcinoma. The tumor was positive for human papilloma virus (HPV). It was staged T1 (stage 1 primary tumor) N0 (no regional lymph nodes metastasis) M0 (no distant metastasis). A computed tomography (CT) scan of the neck showed soft tissue thickening of the left posterolateral pharyngeal mucosal space. It was located at the junction of the nasopharynx and oropharynx abutting the left base of the soft palate. A few enlarged bilateral lymph nodes were noted in the neck. There was also bilateral carotid bulb calcification. Radiation therapy alone was recommended as a treatment choice in order to achieve a higher likelihood of cure and less morbidity. A study by Chen et al1 showed that definitive radiation therapy without chemotherapy can provide higher rate of 3 year overall survival, locoregional control, and distant metastasis-free survival for patients with HPV positive head and neck cancer. Past Medical History: MN has a past medical history of high blood pressure, retinal detachment, right cataract, and gout involving his hands, elbows, knees and toes. Social History: MN is married with two biological sons, two step daughters, and one step son. He is self employed as courier for a transportation company. MN is a smoker and has a history of 54 packs per year. He drinks three cans of beers per day. The patient has a brother with esophageal cancer diagnosed at age 59. He has no other family history of cancer. Medications: MN currently takes Allopurinol, Alodipine, Lisinopril, Indomethacin, and aspirin. He also uses mouthwash and takes Hydrocodone two or three times per day to manage his throat pain. Diagnostic Imaging: MN had CT of the head and neck that demonstrated a mild left pharyngeal mucosal space soft tissue thickening which measured approximately 1 centimeter (cm. This

2 compared with the right side mass measuring 0.5 cm. A few normal sized bilateral lymph nodes were noted in the neck. There was carotid bulb calcification bilaterally without resulting in hemodynamically significant stenosis. The remainder of soft tissues in the neck were unremarkable. Radiation Oncologist Recommendations: MN was recommended a definitive radiation therapy treatment. The potential benefits and risks were discussed in detail with the patient. The patient was strongly advised to quit smoking and agreed to contact his primary physician for help. Smoking during radiation treatment increases the risk of side effects including mucositis, loss of taste, xerostomia, weight loss, fatigue, bone and soft tissue damage, and damage in voice quality.2 It also compromises treatment outcomes by decreasing oxygenation and reducing the effect of radiation. Head and neck cancer patients who continue to smoke during treatment have poor 5-year survival and higher disease recurrence.3 MN was also recommended to stop drinking beer due to the irritative effects of alcohol on the oropharyngeal mucosa. All of his questions were answered to his satisfaction. The patient agreed to proceed with the recommended treatment. He understood that surgery is an option for salvage if radiation therapy fails. He was recommended to have a positron emission tomography (PET)/CT and a dental evaluation prior to simulation. The Plan (Prescription): After examining the patient and reviewing the diagnostic findings, the radiation oncologist decided to proceed with volumetric modulated arc therapy (VMAT). The treatment was prescribed to 6000 centigray (cGy) in 30 fractions to the left oropharynx and involved high-risk regions. A simultaneous prescription of 5400 cGy in 30 fractions was prescribed to the right elective nodal regions. A boost of 1000 cGy in 5 fractions was prescribed to the left tonsil for a total of 7000 cGy in 35 fractions. Patient Setup/Immobilization: MN was simulated in a supine position with his head towards the scanner. His head was set in an extended position on an accufoam (Figure 1). An aquaplast mask was made by warming a thermoplastic mesh in a warm bath and stretching it over the patients face, neck, and shoulders (Figure 1). The customized mask was used to reproduce the same head position and restrict movement during treatment. A shoulder strap was used to pull the shoulders away from the treatment area (Figure 1). MN had a sponge under his knees for comfort. A General Electric (GE) CT unit was used for the simulation. The head and neck images were taken at 0.25 cm slices.

3 Anatomical Contouring: After the simulation was completed, the CT slices were imported into the Varian Eclipse version 10 treatment planning system (TPS). The medical dosimetrist contoured most of the normal structures including the brain, brainstem, eyes, lenses, optic nerves, lungs, mandible, spinal cord, esophagus, larynx, . The radiation oncologist contoured the parotids, oral cavity, inner ears, pituitary gland, submandibular gland, optic chiasm, gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). The PTVs included PTV54, PTV60, and PTV70 (Figure 2). The dental artifacts were contoured and assigned a density equivalent to water. Metal artifacts can distort dose distribution by creating cold and hot spots.4 This correction method can help reduce such complications. The spinal cord was expanded by 0.3 cm in all directions. Avoidance structures were created for organs at risk (OR) that overlapped with the target with 0.2 cm margin around PTV60. This included left parotid, right parotid, mandible, and oral cavity. An avoidance structure was also created for each shoulder. A 1 cm wide ring was constructed 2 cm away from the PTV60. A PTV54-60 structure was constructed by subtracting PTV54 from PTV60. PTV 60 was enlarged by 0.1cm in all direction for optimization purpose. Beam Isocenter/Arrangement: A Varian 21 IX linear accelerator (Linac) was used to treat the patient. During simulation, the radiation oncologist set an isocenter within the treatment site. Three rotational arcs were arranged for the initial treatment, two in clockwise (CC) direction and one in counter clockwise (CCW) direction. The first beam rotated from 181o to 179o with 15o collimator angle and 15 x 17.1 cm field size (Figure 3). The second beam rotated from 179o to 181o with 345o collimator angle and 15 x 17.1 cm field size (Figure 4). The third beam rotated from181o to 179o with 15o collimator angle and 15 x 19.5 cm field size (Figure 5). The boost plan contained two rotational arcs, CC and CCW direction. The first beam rotated from 181o to 179o with 15o collimator angle and 7.8 x 8.7 cm field size (Figure 6). The second beam rotated from179o to 181o with 345o collimator angle and 7.8 x 8.7 cm field size (Figure 7). The couch rotation was set at 0o for all arcs. A 6 mega volt (MV) photon beam was used for all arcs. Treatment Planning: The medical dosimetrist started the initial plan by setting the appropriate gantry rotation, collimator angle, and field size. These were carefully arranged to allow full PTV exposure for each arc. The inverse planning process included clinical goals to the PTVs and planning constraints to the ring, the avoidance structures, and OR. The progressive resolution optimizer (PRO) algorithm within the Eclipse software generated an ideal intensity map with

4 optimal weighting of each control point. The MLC segments, the gantry speeds, and the dose rates of each control point were generated from the ideal intensity map. The plan was reviewed after each optimization and weightings of the objectives were adjusted based on the information retrieved from the dose volume histogram (DVH) and the isodose lines. The final three dimension (3D) dose distribution was evaluated using DVH analysis as well as viewing the 3D dose distribution in multi-plane view and on individual CT slices. The final dose calculation was performed using the analytical anisotropic algorithm (AAA). The plan was finalized with the 95% isodose line covering the PTV54 with a mean dose of 5568 cGy and maximum dose of 6142 cGy located within the PTV and PTV60 with a mean dose of 6156 cGy and maximum dose of 6656 cGy (Figure 8 and 9). After careful review, the physician accepted the treatment plan. The optimization for the boost plan was conducted with a new avoidance structures for the oral cavity 0.2 cm away from PTV70. A 1 cm wide ring was also created 2 cm away from PTV70. PTV70 was enlarged 0.1 cm in all directions for optimization purposes. The plan was optimized multiple times with the necessary changes made to obtain the utmost OR sparing and target coverage. The plan was finalized with the 95% isodose line covering PTV70 with a mean dose of 1018 cGy and maximum dose of 1076 cGy (Figure 8). All of the clinical goals and planning objectives were met for both the initial and boost plan (Figure 9). The cumulative dose to the parotids, spinal cord, brainstem, oral cavity, larynx, and mandible was kept below their dose limit (Figure 9). Quality Assurance (QA)/Physics Check: A monitor unit (MU) check was performed with RadCalc. At this facility, a 5% deviation in MU is the tolerance for all plans. Anything outside of this range needs to be re-calculated and fixed by the medical dosimetrists or physicists prior to the first treatment. Both the initial plans and the boost plan were approved with an individual MU difference less than 2% (Figures 10 and 11). The rapid arc QAs were generated using the AAA of each arc. The intensity maps were calculated in a flat solid water phantom. The intensity maps were exported to be compared to measurements obtained with the SunNuclear MapCheck device. The initial plan passed the QA with 98% and the boost plan with 98.4%. Conclusion: This case has allowed me to learn the effect of smoking on treatment outcomes. MN has smoked a pack of cigarettes per day for 54 years and continued to smoke after his

5 diagnosis. The radiation oncologist has counseled the patient regarding smoking and the importance of quitting as soon as possible. This will benefit the patient by increasing the survival rate, decreasing the risk of secondary cancers, and improving his quality of life. Smoking during treatment can increase toxicity and affect his treatment outcome. Smoking impairs delivery of oxygen to tissues by constricting small vessels and increasing carboxyhemoglobin levels.5,6 This can compromise the effect of radiation by interfering with the radiosensitivity of tumor cells.

6 Figures

Figure 1. Patients setup position with accufoam, aquaplast mask, and shoulder strap

Figure 2. Axial, coronal, and sagittal view of the PTVs. Yellow represents PTV70, orange represents PTV60, and purple represents PTV54

Figure 3. Collimator angle and field size of the first arc for the initial plan covering PTV54 and PTV60

Figure 4. Collimator angle and field size of the second arc for the initial plan covering PTV54 and PTV60

Figure 5. Collimator angle and field size of the third arc for the initial plan covering PTV54 and PTV60

Figure 6. Collimator angle and field size of the first arc for the boost plan covering PTV70

Figure 7. Collimator angle and field size of the first arc for the boost plan covering PTV70

Figure 8a. Axial view of dose distribution for the cumulative plan. 95% isodose line (blue) conformity around PTV54, 95% isodose line (green) conformity around PTV60, 95% isodose line (red) conformity around PTV70

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Figure 8b. Coronal view of dose distribution for the cumulative plan. 95% isodose line (blue) conformity around PTV54 (purple), 95% isodose line (green) conformity around PTV60, 95% isodose line (red) conformity around PTV70

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Figure 8c. Sagittal view of dose distribution for the cumulative plan. 95% isodose line (blue) conformity around PTV54, 95% isodose line (green) conformity around PTV60, 95% isodose line (red) conformity around PTV70

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Figure 10. DVH of the cumulative plan demonstrating dose distribution to PTVs and OR

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Figure 11. MU check of the initial plan

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Figure 12. MU check of the boost plan

15 References 1. Chen AM, Zahra T, Daly ME, et al. Definitive radiation therapy without chemotherapy for human papillomavirus-positive head and neck cancer. Head Neck. 2013;35(11):16521656. doi:10.1002/hed.23209 2. Tobacco Use During Cancer Treatment. Cancer Web Site. http://www.cancer.net/allabout-cancer/risk-factors-and-prevention/tobacco/tobacco-use-during-cancer-treatment. Accessed Oct. 21 2013. 3. Chen AM, Chen LM, Vaughan A, et al. Tobacco smoking during radiation therapy for head and neck cancer is associated with unfavorable outcome. Int J Radiat Oncol Biol Phys. 2011;79(2):414-419. 4. Kim Y, Tome WA, Todd MB, et al. The impact of metal artifacts on head and neck IMRT dose distribution. Radiother Oncol.2006;79(2):198-202. 5. Jensen JA, Goodson WH, Hopf HW, et al. Cigarette smoking decreases tissue oxygen. Arch Surg. 1991;126(9):1131-1134. 6. Wald NJ, Idle M, Bailey A. Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels. Thorax. 1981;36(5):366-369.

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