Proton Therapy for Thymic Malignancies: Multi-institutional Patterns-of-Care and Early Clinical Outcomes from the Proton Collaborative Group Registry & UF Catherine Mercado, MD Department of Radiation Oncology University of Florida College of Medicine October 23rd, 2017

Disclosures None of the authors have conflicts of interest

Background Thymoma and thymic carcinoma are rare malignancies arising in the anterior mediastinum from the thymus. Median age of diagnosis: 40-60 years old Treatment: Surgery +/- RT, chemo If unresectable, chemoRT

Background Long term survivorship common, causing concerns for radiotherapy related late side effects (i.e. cardiac disease or secondary malignancies) OS (RT vs. no-RT) 5yr: 95% vs. 90% 10yr: 86% vs. 79 % Rimner et al. J Thorac Oncol. 2016

Background NCCN Guidelines RT Techniques for TM: “...Since these patients are younger and mostly long-term survivors, the mean dose to the total heart should be as low as reasonably achievable.” Proton therapy (PT) reduces the radiation dose to organs at risk, potentially improving disease control and decreasing long-term toxicity

Colorwash isodose distribution for IMRT (left) and PT (right). Background Photon vs. Proton: Dosimetry demonstrates reduced RT dose to the OARs with PT Colorwash isodose distribution for IMRT (left) and PT (right).  DVH representing the percentage of each organ irradiated at each RT dose level with IMRT or PT. Figura et al., J Thorac Oncol. 2013 May;8(5):e38-40.

Background Parikh et al. demonstrated significant reductions in heart, lung, and esophagus dose in PT plan compared to analogous IMRT plan Parikh et al., Clin Lung Cancer. 2016 Vogel et al. assessed risk of predicted secondary malignancies (SMNs) following adjuvant proton vs. photon therapy in thymoma patients Results: 5 excess SMNs per 100 patients can potentially be avoided using protons vs. photons Vogel et al., Int J Radiation Oncol Biol Phys, Vol. 99, 2017

Objective This study reports on the patterns-of-care and early clinical outcomes of patients treated with PT for thymoma and thymic carcinoma.

Methods From January 2008 to March 2017 30 patients received post-operative or definitive proton therapy for thymoma or thymic carcinoma All patients were treated on the institutional review board-approved University of Florida outcomes tracking protocol or PCG registry Clinical outcomes, pathology, treatment dose, acute toxicities, and follow-up information were analyzed.

Patient Characteristics Thymoma Thymic Carcinoma Characteristic Thymoma (n=21) Median Age 52 years (range, 23-72) Median RT dose 54 CGE (range, 45-70) Post-operative RT 86 % (18) Definitive RT 14 % (3) Adjuvant chemotherapy 24 % (5) Characteristic Thymic Carcinoma (n=9) Median Age 65 years (range, 38-88) Median RT dose 60 CGE (range, 45-70) Post-operative RT 67 % (6) Definitive RT 33 % (3) Adjuvant chemotherapy

Clinical Outcomes Median follow-up: 22 months (range, 3-60 months) Local recurrence: 2 thymoma and 1 thymic carcinoma patient Median time from completion of PT to local recurrence: 13 months (range, 2-26) Patient deaths: 3 1 patient died who also had locally recurrent thymic carcinoma 1 patient died due to metastatic disease 1 patient died due to intercurrent disease No patient experienced grade ≥3 toxicities after PT

3 patients with recurrence after PT Disease Status at Last Follow-Up Clinical Outcomes 3 patients with recurrence after PT Patient Diagnosis Def vs. Post-op PT Dose Time to Recurrence (months) Type of Recurrence Disease Status at Last Follow-Up 1 Thymic Ca Definitive 70 CGE 13 months Local and Distant (In and out of field) Dead 2 Thymoma Post-op 50 CGE 2 months Local Only (subpleural nodules, out of field) Alive 3 45 CGE 26 months 1 patient in cohort had oligometastatic disease prior to PT, at last follow-up patient died with distant metastasis

Discussion Single institution, 27 patients Median follow-up: 2 years No patient experienced grade ≥3 toxicities At 3 years: Regional control 96%, Distant control 74%, Overall Survival 94% Vogel et al., Radiotherapy and Oncology 118 (2016) 504–509

Discussion Comparable Results: Institution Regional Control Distant Control Overall Survival Toxicity PCG + UF (22 mo f/u) 90% 93% Grade ≥3 toxicities UPenn (36 mo f/u) 96% 74 % 94 % Vogel et al., Radiotherapy and Oncology 118 (2016) 504–509

Conclusions Adjuvant and definitive PT is being used in the treatment of thymic malignancies. Early results demonstrate an acceptable rate of recurrence with a tolerable toxicity profile. Longer follow-up and a larger patient cohort are needed to confirm these findings.

Acknowledgements Questions Bradford Hoppe, MD Randal Henderson, MD Amanda Price PCG Collaborators: Henry Tsai, MD (NJ Procure Proton Therapy Center) Carlos Vargas, MD (Mayo Clinic Arizona) George E. Laramore, MD, PhD (University of Washington) Shahed Badiyan, MD (University of Maryland) William Hartsell, MD (Northwestern Chicago Proton Center) Gary Larson, MD (Oklahoma City Procure Proton Therapy Center) Questions