Clinical Outcomes of Patients with Stage II-III Non-Small Cell Lung Cancer (NSCLC) Treated with Proton Beam Therapy (PBT) on the Proton Collaborative Group (PCG) Prospective Registry Trial

Abstract

RTOG 0617 demonstrated poorer overall survival (OS) for patients receiving dose-escalated photon-based radiation therapy with concurrent chemotherapy possibly due to increased toxicity. We assessed the outcomes of patients enrolled on the PCG registry trial with stage IIA-IIIB NSCLC treated with PBT. We hypothesized that PBT could be delivered to a high-risk, poor prognostic locally advanced NSCLC population with limited acute and late high-grade toxicity. Between 2010 and 2015, 96 consecutive patients were treated with PBT with curative intent at 4 PCG institutions. Approximately 5 out of every 6 patients were not eligible for PCG-LUN005 or RTOG 1308 study due to poor pulmonary function, co-morbidities, or other contraindications. Freedom from recurrence (FFR) and OS were estimated from PBT completion using the Kaplan–Meier method. Median age was 72 (range, 51-93) years, including 18% over age 80. Sixty-three percent were male and 95% white. Ninety-three percent were current or former smokers. Twenty percent had an ECOG performance status of 2 or 3. Patients had stage IIA (14%), IIB (8%), IIIA (54%), or IIIB (24%) disease. Patients received definitive (83%) or adjuvant (17%) PBT. Eighty-five percent received chemotherapy, including 70% treated with concurrent chemoradiation. A median dose of 70 Gy(RBE) in 35 fractions was administered (range in patients that completed PBT, 48-75 Gy(RBE)). Median follow-up was 10.2 months for all patients and 16.5 months for living patients. Ninety-three percent completed PBT as planned. First site of recurrent disease was locoregional in 21% and distant in 11%. Estimated median and 1- and 2-year OS were 13.2 months, 53.4%, and 39.4%, respectively. Estimated median and 1-year FFR were 13.1 months and 51.8%, and 39.1% respectively. Acute grade 3 and 4 toxicities occurred in 6% (dyspnea, dehydration, radiation dermatitis, skin pain, esophagitis and fatigue) and 1% (myocardial infarction), respectively. Five patients died during or shortly after PBT, (3 due to cardiac arrest/myocardial infarction and 2 for unknown reasons), but only one was felt to be possible or probably related to treatment. Late grade 3 late toxicities occurred in 3% of patients (dyspnea and laryngeal hemorrhage). There was no late grade 4 toxicity. Specifically, grade 3 esophagitis and pneumonitis/dyspnea occurred in 1% and 3% of patients, respectively. Despite being delivered to a generally high-risk, unfavorable population with locally advanced NSCLC, PBT results in limited toxicity. Ongoing prospective trials will further assess the long-term efficacy and toxicity of PBT for stage II-III NSCLC. 5 Gy(RBE).