Risk-adapted use of thoracic radiotherapy in stage IV non-small cell lung cancer: a multicenter prognostic model study.

BACKGROUND: Survival benefit of thoracic radiotherapy (TRT) in patients with stage IV non-small cell lung cancer (NSCLC) receiving first-line chemo-immunotherapy remains uncertain. This study developed and validated an overall survival (OS) prediction model and assessed whether TRT benefit varied across risk strata. METHODS: Patients with stage IV NSCLC treated with first-line chemo-immunotherapy were enrolled. A nomogram was developed using baseline clinical variables to calculate individual risk scores. Patients were classified into high- and low-risk groups according to the median nomogram-derived score. OS was compared between ICI and ICI+TRT groups in the overall cohort and risk subgroups. Treatment-by-risk interaction, 1:1 propensity score matching (PSM), treatment response, TRT pattern, BED10, and metastatic burden subgroup analyses, and safety assessments were performed. RESULTS: Among 514 patients, 284 without TRT were assigned to training and internal validation cohorts at a 7:3 ratio, and 84 non-TRT patients formed an external validation cohort. ECOG performance status, alkaline phosphatase, total protein, platelet-to-lymphocyte ratio, and systemic immune-inflammation index were selected as optimal prognostic factors. The nomogram showed good 1- and 2-year OS discrimination, calibration, and clinical utility. Using a median risk score of 103.1, TRT improved OS only in low-risk patients (HR 0.456, 95% CI 0.285-0.730; P = 0.0011), not high-risk patients (HR 0.914, 95% CI 0.556-1.503; P = 0.7239), with consistent findings after PSM. Treatment-by-risk interaction was significant (P = 0.0309). Grade 1-2 pneumonitis was higher with ICI+TRT than ICI alone (28.8% vs. 10.3%; P < 0.001), without significant differences in severe pneumonitis or immune-related adverse events. CONCLUSION: TRT benefit was risk-dependent, improving OS in low-risk but not high-risk patients.