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.