Salvage thoracic reirradiation for recurrent non-small cell lung cancer: Clinical efficacy and the impact of consolidative immunotherapy

PURPOSE: To describe clinical outcomes in a large patient cohort treated with salvage thoracic reirradiation (reRT) for isolated locoregional recurrence of non-small cell lung cancer (NSCLC). METHODS: Between 2011 and 2021, 1219 patients received thoracic radiotherapy for NSCLC; 130 patients underwent reRT, with doses ranging from 60-72 Gy. Primary outcomes were overall survival (OS), progression-free survival (PFS), and reRT toxicity; secondary outcomes were locoregional failure (LRF) and distant failure (DF). The Kaplan-Meier method and cumulative incidence with death as a competing risk were used for analysis, with multivariable modeling via Cox proportional hazards. Toxicity outcomes included grade 3 + non-hematologic event, hospitalization within 90 days of reRT, and grade 5 toxicity per Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: Median OS and PFS for the entire cohort were 17.4 months (95 % CI 14.1-22.9) and 8.1 months (95 % CI 6.7-10.8), respectively. 3-year OS was 25.9 % (95 % CI 19.3-34.8 %). The 3-year cumulative incidence of DF and LRF were 44 % and 46 %, respectively. Recipients of consolidative immunotherapy after reRT had improved OS (27.8 months [95 %CI 18.4-not reached] vs 15.8 months [95 %CI 12.1-22.1]; p = 0.035) and locoregional-free survival (22.8 months [95 %CI 9.8-not reached] vs 8.8 months [95 %CI 7.6-12.6]; p = 0.009). Multivariable analysis showed consolidative immunotherapy (HR 0.56, 95 %CI 0.32-1.03, p = 0.065) and hospitalization within 90 days of reRT (HR 2.03, 95 %CI 1.24-3.33, p = 0.005) were associated with OS. Nine patients (6.9 %) experienced grade 5 toxicities. CONCLUSION: Thoracic reRT is a safe treatment option associated with long-term cure in select patients. Immunotherapy consolidation was associated with improved clinical outcomes.