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

• Higher EDIC was independently associated with worse OS, PFS, and LRC. • EDIC > 6 Gy was associated with shorter time to brain metastasis. • Minimizing EDIC may improve outcomes in patients treated with CCRT and durvalumab. 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. [ABSTRACT FROM AUTHOR]