Assessment of the Effective Dose to Immune Cells as an Independent Predictor of Durvalumab Response in Patients With Non-Small Cell Lung Cancer After Chemoradiotherapy: A Multicenter Study.

Abstract

The effective dose to immune cells-radiotherapy course-adjusted (EDRIC) is a dosimetry-based metric that estimates radiation exposure to circulating immune cells during radiotherapy. Elevated EDRIC is linked to lymphopenia, immune dysfunction, and poor tumor control in unresectable non-small cell lung cancer (NSCLC) after chemoradiation. However, it is unclear if EDRIC directly correlates with clinical outcomes and particularly with durvalumab consolidation, or if confounding factors drive this association. This study examined whether EDRIC independently correlates with progression-free survival (PFS). Data from 286 patients with unresectable stage III NSCLC treated with definitive-intent radiation therapy between 2017 and 2024 at 3 tertiary centers were collected. EDRIC was calculated using mean heart, lung, body doses, and the number of fractions. Maximally selected rank statistics identified the optimal EDRIC cutoff for PFS. Univariable and multivariable Cox regression models were used to assess the association between EDRIC and clinical outcomes. Following the exclusion of patients who did not meet the inclusion criteria, 251 patients remained in the final analysis dataset. Using a cutoff of 9.57 Gy, 53 patients were classified as having high EDRIC and 198 as low EDRIC. Patients with low EDRIC had significantly longer median PFS (23.7 vs 11.7 months; hazard ratios (HR) 0.56; 95% CI, 0.39-0.82; P = .003). In a multivariable analysis including EDRIC, PD-L1 (programmed death ligand-1) expression, N stage (N3 vs N0-2), and PTV (planning target volume), lower EDRIC remained directionally associated with longer PFS (low vs high HR = 0.67; 95% CI, 0.45-1.01; P = .053), PD-L1 positive status remained associated with longer PFS (vs PD-L1 negative: HR = 0.64; 95% CI, 0.44-0.94; P = .021), and N3 was directionally adverse (HR = 1.56; 95% CI, 0.99-2.46; P = .054). In patients receiving durvalumab after chemoradiation for unresectable stage III NSCLC, lower EDRIC was associated with longer PFS. This effect was limited to patients with positive PD-L1 tumors.