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Background  Preclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC).    Methods  The National Cancer Database was queried for patients with stage IV NSCLC receiving chemotherapy or immunotherapy from 2013 to 2014. RT modality was classified as stereotactic radiotherapy (SRT) to intra- and/or extracranial sites or non-SRT external beam RT (EBRT). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards models.    Results  In total, 44,498 patients were included (13% immunotherapy, 46.8% EBRT, and 4.7% SRT). On multivariate analysis, immunotherapy (hazard ratio [HR]:0.81, 95% confidence interval [CI]:0.78–0.83) and SRT (HR:0.78, 95%CI:0.70–0.78) independently associated with improved OS; however, the interaction term for SRT + immunotherapy was insignificant ( p  = 0.89). For immunotherapy patients, the median OS for no RT, EBRT, and SRT was 14.5, 10.9, and 18.2 months, respectively ( p  < 0.0001), and EBRT (HR:1.37, 95%CI:1.29–1.46) and SRT (HR:0.78, 95%CI:0.66–0.93) associated with OS on multivariate analysis. In the SRT subset, median OS for immunotherapy and chemotherapy was 18.2 and 14.3 months, respectively ( p  = 0.004), with immunotherapy (HR:0.82, 95%CI:0.69–0.98) associating with OS on multivariate analysis. Furthermore, for patients receiving SRT, biologically effective dose (BED) > 60 Gy was independently associated with improved OS (HR:0.79, 95%CI:0.70–0.90,  p  < 0.0001) on multivariate analysis with a significant interaction between BED and systemic treatment ( p  = 0.008).    Conclusions  Treatment with SRT associated with improved OS for patients with metastatic NSCLC irrespective of systemic treatment. The high survival for patients receiving SRT + immunotherapy strongly argues for evaluation in randomized trials.

Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer: a National Cancer Database analysis