Phase II study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III non-small cell lung cancer.

Abstract

7017 Background: Concurrent chemotherapy and radiotherapy to 60 to 66 Gy have been standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) with median survival time of about 17 months and with more than 50% patients developing grade 3 toxicities. We sought here to improve the toxicity and survival in this group of patients by using proton-beam therapy to escalate the radiation dose to the tumor. We report early results of a phase II study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Methods: Forty-four patients with stage III NSCLC were enrolled our phase II clinical trial and treated with 74 Gy(RBE) proton therapy with weekly carboplatin (AUC 2) and paclitaxel (50 mg/m2). Disease was staged with positron emission tomography/computed tomography (PET/CT) and treatments were simulated with 4-dimensional CT to account for tumor motion. Protons were delivered as passively scattered beams and treatment simulation was repeated during the treatment process to determine the need for adaptive re-planning. Results: Median follow-up was 19.7 months (range, 6.1-44.4 months) and median overall survival was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n=5), esophagitis (n=5), and pneumonitis (n=1). Nine patients (20.5%) experienced local disease recurrence but only 4 (9.1%) had isolated local failure. Four patients (9.1%) had regional lymph node recurrence but only one (2.3%) had isolated regional recurrence. Nineteen patients (43.2%) developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Conclusions: High-dose proton therapy with concurrent chemotherapy is well tolerated and the 29.4-month median survival time and 20.5% total local failure rate are encouraging for inoperable stage III NSCLC. These findings lead to an ongoing prospective phase II randomized study comparing proton therapy vs. intensity-modulated (photon) radiation therapy to 74 Gy with concurrent chemotherapy for stage III NSCLC.