Long-term Outcomes of Proton Beam Re-irradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer

Abstract

The management of locoregionally recurrent NSCLC in the setting of prior radiation therapy is challenging. Proton radiotherapy (PRT) may be ideally suited to minimize toxicity to previously irradiated organs. We report the long-term outcomes of PRT for NSCLC reirradiation in a prospective study. Between October 2010 and December 2015, 41 patients who completed an initial course of radiotherapy at least 3 months prior for lung cancer with local and/or regional recurrence of NSCLC in or near their prior radiation field were treated with PRT with or without concurrent systemic therapy, at the University of Pennsylvania. Patients were stratified into cohorts by tumor volume (< 0r > 250 cm3 clinical target volume (CTV)). Toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Survival outcomes were estimated by using Kaplan-Meier analysis. Thirty-six patients (88%) completed the planned course of reirradiation. Median age in the cohort was 65 years (range 47-86). There were 5 patients with CTV ≥250 cm3 and this cohort was closed to enrollment owing to infeasibility in August 2012. Median time between radiation courses was 19 months (4- 151). The median total dose of reirradiation was 6660 cGy (3000-7200), and the median prior dose was 6660 cGy (3260-7200). PET/CT simulation was used for planning in all patients. Concurrent systemic therapy was delivered to 80% of patients. Seven patients had local (17%) and nine had regional (22%) recurrence after reirradiation. Distant metastases developed in fourteen patients (34%). There was one grade 5 toxicity (pleural effusion, hypoxia), and 48% had a grade 3 or higher acute or late toxicities. The 2- and 5-year rates of overall survival were 34% and 21%, respectively. In this prospective study, PRT for recurrent NSCLC is feasible with encouraging long-term survival but significant risk of toxicities. Providers should remain cautious in reirradiating NSCLC, paying close consideration to tumor volume. A prospective phase II trial is currently underway assessing proton reirradiation with concurrent chemotherapy followed by immunotherapy (NCT03087760).