Investigating prognostic factors of abscopal effect in combined thoracic radiation therapy and immune checkpoint inhibitors for stage IV non–small cell lung cancer

Purpose: This study aimed to identify independent predictors of infield and outfield progression in stage IV non–small cell lung cancer (NSCLC) patients receiving thoracic radiation therapy (RT) combined with immune checkpoint inhibitors (ICI) and evaluate whether local tumor response mediates systemic disease control.Materials and Methods: This retrospective study included 98 patients with stage IV NSCLC receiving thoracic RT combined with ICI between January 2018 and December 2023. Infield and outfield progression were analyzed using a competing risk analysis and survival outcomes were estimated using the Kaplan-Meier method.Results: With a median follow-up time of 11.2 months (range, 1.4 to 84.4), the median overall survival was 24.9 months (95% confidence interval [CI], 18.4 to 31.3) and the median progression-free survival was 4.5 months (95% CI, 3.5 to 6.7). Infield objective response rate was 77.6%. On multivariable analysis, equivalent doses in 2 Gy fractions ≥40 Gy (subdistribution hazard ratio [SHR], 0.32; p = 0.002), concurrent chemotherapy with ICI (SHR, 0.30; p = 0.005), and squamous histology (SHR, 2.33; p = 0.025) were independent predictors of infield progression. Infield response (SHR, 0.28; p = 0.001), ICI-first sequencing (SHR, 0.27; p = 0.002), and Eastern Cooperative Oncology Group performance status 2 (SHR, 5.32; p < 0.001) independently predicted outfield progression.Conclusion: Higher RT dose and infield tumor response independently predicted infield and outfield disease control, consistent with a potential dose-dependent abscopal association in stage IV NSCLC treated with thoracic RT and ICI.