Proton therapy for thymic malignancies: multi-institutional patterns-of-care and early clinical outcomes from the proton collaborative group and the university of Florida prospective registries.

Objective: Thymic malignancies (TM) are rare tumors with long-term survivorship, causing concerns for radiotherapy-related late side effects. Proton therapy (PT) reduces the radiation dose to organs at risk, potentially decreasing long-term toxicities while preserving disease control. We report patterns-of-care and early clinical outcomes after PT for thymoma and thymic carcinoma. Methods: Between January 2008 and March 2017, 30 patients with TMs enrolled on one of two IRB-approved prospective protocols and received postoperative or definitive PT. Clinical outcomes, pathology, treatment dose, toxicities, and follow-up information were analyzed. Results: Twenty-two thymoma patients with a median age of 52.1 years (range, 23-72) received a median RT dose of 54 Gy (RBE) (range, 45-70) either postoperatively (91%) or definitively (9%); 23% received adjuvant chemotherapy. Among eight thymic carcinoma patients, the median age was 65.5 years (range, 38-88) and median RT dose was 60 Gy (RBE) (range, 42-70) delivered postoperatively (75%) or definitively (25%); 50% received chemotherapy. Median follow-up for all patients was 13 months (range, 2-59 months). Five patients relapsed, one locally (3%). Three patients died of disease progression, including two thymomas and one thymic carcinoma patient; a fourth died of intercurrent disease. One patient with thymic carcinoma and 1 with thymoma are alive with disease. No patients treated with PT for their initial disease (de novo) experienced grade ≥3 toxicities. The most common grade 2 toxicities were dermatitis (37%), cough (13%), and esophagitis (10%). Conclusion: Adjuvant and definitive PT are being used in the treatment of TMs. Early results of the largest such cohort reported to date demonstrates an acceptable rate of recurrence with a favorable toxicity profile. Longer follow-up and a larger patient cohort are needed to confirm these findings.

Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy.

PURPOSE: To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT). MATERIAL AND METHODS: From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1 < 1.0 or O2 dependency, prior lung cancer, prior lung surgery, prior 2nd cancer in the past 3 years, and prior chest irradiation were evaluated. All patients received standard fractionation of 1.8-2 Gy(RBE) (median dose, 70 Gy[RBE]). Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. The impact of unfavorable factors was analyzed in Cox regression models. RESULTS: Twenty-six percent were favorable-risk, while 42%, 22%, and 10% had 1-, 2-, or ≥3 unfavorable factors. The 2-year OS was 52% and 45% (p = .8522), and 2-year PFS was 21% and 44% (p = .0207), for favorable and unfavorable risk patients, respectively. Among patients with stage III-IV, only PS ≥2 adversely impacted OS (p = .0015). CONCLUSION: Most patients treated with PT for LA-NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients. Enrollment in future clinical trials may improve if eligibility is less restrictive.

Rationale and early outcomes for the management of thymoma with proton therapy.

BACKGROUND: Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution. METHODS: From January 2008 to March 2017, six patients with de novo Masaoka stages II-III thymic malignancies were treated with PT on an IRB-approved outcomes tracking protocol. Patients were evaluated weekly during treatment, then every 3 months for 2 years, then every 6 months for 3 more years, and then annually for CTCAE vs. four toxicities and disease recurrence. Comparison intensity-modulated radiotherapy (IMRT) plans were developed for each patient. Mean doses to the heart, esophagus, bilateral breasts, lungs, and V20 of bilateral lungs were evaluated for the two treatment plans. RESULTS: At last follow-up (median follow-up, 2.6 years), there were two patients with recurrences, including metastatic disease in the patient treated definitively with chemotherapy and PT without surgery and a local-regional recurrence in the lung outside the proton field in one of the post-operative cases. No patients with de novo disease experienced grade ≥3 toxicities after PT. The mean dose to the heart, lung, and esophagus was reduced on average by 36.5%, 33.5%, and 60%, respectively, using PT compared with IMRT (P<0.05 for each dose parameter). CONCLUSIONS: PT achieved superior dose sparing to the heart, lung, and esophagus compared to IMRT for thymic malignancies. Patients treated with PT had few radiation-induced toxicities and similar survival compared to historic proton data.