Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A YYY Phase 1/2 Trial.

Abstract

Introduction: Hypofractionated radiotherapy has been safely implemented into the treatment of early-stage non-small cell lung cancer (NSCLC), but not locally advanced (LA-) NSCLC due to prohibitive toxicities with photon therapy. Proton therapy, however, may allow for safe delivery of hypofractionated radiotherapy. We sought to determine whether hypofractionated proton therapy with concurrent chemotherapy improves overall survival.

Methods & materials: The YYY conducted a phase 1/2 single-arm nonrandomized prospective multicenter trial from 2013 through 2018. Thirty-two patients were consented; 28 were eligible for on-study treatment. Patients had AJCCv7 stage II or III unresectable NSCLC and received hypofractionated proton therapy at 2.5-4 Gy per fraction to a total 60 Gy with concurrent platin-based doublet chemotherapy. The primary outcome was 1-year overall survival comparable to that reported for RTOG 9410 of 62%.

Results: The trial closed early due to slow accrual, in part, from a competing trial, NRG 1308. Median patient age was 70 (range, 50-86) years. Patients were predominantly male (N=20), white (N=23), and prior smokers (N=27). Most had stage III NSCLC (N=22), 50% of whom had adenocarcinoma. After a median follow-up of 31 months, the 1- and 3-year overall survival rates were 89% and 49%, and progression-free survival rates were 58% and 32%, respectively. No acute grade 3 or higher esophagitis occurred. Only 14% developed a grade 3 or higher radiation-related pulmonary toxicity.

Conclusion: Hypofractionated proton therapy delivered at 2.5-3.53 Gy per fraction to a total 60 Gy with concurrent chemotherapy provides promising survival and additional examination through larger studies may be warranted.