Efficacy and safety of immunoradiotherapy for advanced non-small cell lung cancer: a retrospective comparative cohort study.

Background: Treatment of radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) may remarkably improve the prognosis in patients with metastatic non-small cell lung cancer (NSCLC). However, the treatment time of RT, irradiated lesion and the optimum combined scheme, have not been fully determined. Methods: Data regarding overall survival (OS), progression-free survival (PFS), treatment response, and adverse events of 357 patients with advanced NSCLC treated with ICI alone or in combination with RT prior to/during ICI treatment were retrospectively collected. Additionally, subgroup analyses for radiation dose, time interval between RT and immunotherapy, and number of irradiated lesions were performed. Results: Median PFS of the ICI alone and ICI + RT groups was 6 and 12 months, respectively (P<0.0001). The objective response rate (ORR) and disease control rate (DCR) were significantly higher in the ICI + RT group than in the ICI alone group (P=0.014; P=0.015, respectively). However, OS, the distant response rate (DRR), and the distant control rate (DCRt) did not differ significantly between the groups. Out-of-field DRR and DCRt were defined in unirradiated lesions only. Compared with RT application prior to ICI, its application concomitant with ICI led to higher DRR (P=0.018) and DCRt (P=0.002). Subgroup analyses revealed that single-site, high biologically effective dose (BED) (≥72 Gy), planning target volume (PTV) size (<213.7 mL) RT groups had better PFS. In multivariate analysis, PTV volume [≥213.7 vs. <213.7 mL: hazard ratio (HR), 1.89; 95% confidence interval (CI): 1.04-3.42; P=0.035] was an independent predictor of immunotherapy PFS. Additionally, radio-immunotherapy increased the incidence rate of grade 1-2 immune-related pneumonitis compared with ICI alone. Conclusions: Combination therapy using ICIs and radiation may improve PFS and tumor response rates in advanced NSCLC patients regardless of programmed cell death 1 ligand 1 (PD-L1) level or previous treatments. However, it may increase the incidence of immune-related pneumonitis.