Impact of radiation dose to the immune cells in unresectable or stage III non-small cell lung cancer in the durvalumab era

Higher estimated radiation doses to immune cells (EDIC) have correlated with worse overall survival (OS) in patients with locally-advanced non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, which established consolidative durvalumab as standard-of-care. Here, we examine the prognostic impact of EDIC in the durvalumab era.This single-institution, multi-center study included patients with unresectable stage II/III NSCLC treated with chemoradiation followed by durvalumab. Associations between EDIC [analyzed continuously and categorically (≤6 Gy vs > 6 Gy)] and OS, progression-free survival (PFS), and locoregional control (LRC) were evaluated by Kaplan-Meier and Cox proportional methods.100 patients were included with median follow-up of 23.7 months. The EDIC > 6 Gy group had a significantly greater percentage of stage IIIB/IIIC disease (76.0 % vs 32.6 %; p < 0.001) and larger tumor volumes (170 cc vs 42 cc; p < 0.001). There were no differences in early durvalumab discontinuation from toxicity (24.1 % vs 15.2 %; p = 0.27). Median OS was shorter among the EDIC > 6 Gy group (29.6 months vs not reached; p < 0.001). On multivariate analysis, EDIC > 6 Gy correlated with worse OS (HR: 4.15, 95 %CI: 1.52-11.33; p = 0.006), PFS (HR: 3.79; 95 %CI: 1.80-8.0; p < 0.001), and LRC (HR: 2.66, 95 %CI: 1.15-6.18; p = 0.023). Analyzed as a continuous variable, higher EDIC was associated with worse OS (HR: 1.34; 95 %CI: 1.16-1.57; p < 0.001), PFS (HR: 1.52; 95 %CI: 1.29-1.79; p < 0.001), and LRC (HR: 1.34, 95 %CI: 1.13-1.60; p = 0.007).In the immunotherapy era, EDIC is an independent predictor of OS and disease control in locally advanced NSCLC, warranting investigation into techniques to reduce dose to the immune compartment.