Oral 2.01: Proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma

Background: Radiation therapy is a critical component of treatment for thymic tumors. However, radiation-induced toxicity may reduce benefit, particularly in the adjuvant setting. Proton beam therapy (PBT), due to its characteristic Bragg peak, is ideally suited to treat the anterior mediastinum while sparing organs at risk. To date, PBT to treat thymic tumors has only been reported in three single-patient case studies. In this study, we evaluated patterns of failure and toxicity in patients treated for thymoma and thymic carcinoma using PBT and hypothesized that PBT can achieve excellent local control with limited high grade toxicity.

Methods: All patients with thymoma or thymic carcinoma treated with PBT between 2011–2015 were analyzed. Either double scattered proton therapy (DS-PT) or pencil beam scanning (PBS) were used. Toxicity was assessed using CTCAE v 4.2. Local control, distant control, and overall survival were analyzed by the Kaplan-Meier method from the time of PBT completion.

Results: Twenty-seven patients were included. Patients were a median age of 56 years, predominantly female (56%), and had thymoma (85%) or thymic carcinoma (15%). They were treated with definitive (22%) or salvage (15%) PBT or adjuvant (63%) PBT following resection with predominantly close (23%) or positive (50%) margins. Forty-one percent also received chemotherapy. Patients were treated to a median of 61.2 Gy (range 50.4–70.2 Gy) using DS-PT (85%) or PBS (15%). Median mean lung dose, volume of lung receiving ≥20 Gy (V20), and V5 were 98 cGy (1–2,050 cGy), 18% (0–38%), and 26.2% (0–55%). Median mean heart and esophagus doses were 1,065 cGy (105–3,356cGy) and 1,072cGy (0–4,655 cGy). No patient experienced grade ≥3 acute or chronic toxicity. Acute grade ≥2 toxicities included fatigue (11%), esophagitis (7%), dermatitis (37%), and pneumonitis in one patient (4%) who received 2 prior thoracic radiotherapy courses. Late grade ≥2 toxicity was limited to a single patient with chronic dyspnea (grade 2). At a median follow-up of 1.8 years, 100% local control was achieved. Regional control rates at 1, 2, and 3 years were 96% (95% CI, 76–99%) and distant control was 85% (95% CI, 59–95%), 85% (95% CI, 59–95%), and 74% (95% CI, 41–90%). Two unresectable patients (B3, C histologies) died from disease progression, with overall survival at 1, 2, and 3 years of 96% (95% CI, 73–99%), 89% (95% CI, 61–97%), and 89% (95% CI, 61–97%).

Conclusions: PBT in the definitive, adjuvant, and salvage treatment of thymoma and thymic carcinoma has very low acute and chronic toxicity and excellent 3-year outcomes. Longer follow-up and additional studies are required to determine whether PBT has improved clinical outcomes over photon therapy.

Keywords: Thymoma; thymic carcinoma; proton therapy; external beam radiation