The efficacy and toxicity of TRT on metastatic NSCLC in patients treated with targeted therapy and chemoimmunotherapy

Abstract Purpose The role of thoracic radiotherapy (TRT) combined with first-line systemic therapy for metastatic non-small cell lung cancer (NSCLC) remains controversial. Its application is not routinely recommended due to inconsistent efficacy and toxicity risks. This study aims to identify specific patients most likely to benefit from TRT in advanced NSCLC. Methods A cohort included 523 patients with metastatic NSCLC from 2019–2024. Kaplan–Meier curves and log-rank tests were used to analyze progression-free survival (PFS) and overall survival (OS). Risk factors were identified using univariate and multivariate Cox regression analysis. Results The entire cohort median OS was 60 months and median PFS was 22 months. TRT improved both PFS (25 vs. 13 months, P < 0.001) and OS (Not Reached NR vs. 46 months, P < 0.001). In the targeted therapy group, TRT improved PFS (27 vs. 13 months, P < 0.001) and OS (NR vs. 47 months, P < 0.001). In the chemoimmunotherapy group, TRT improved OS (NR vs. 41 months, P = 0.042) but not PFS (18 vs. 14 months, P = 0.115). Exploratory analysis found TRT increased hematologic toxicity (e.g., ≥ grade 2 lymphopenia: 67.18% vs. 11.33%, P < 0.001) and pneumonitis (any grade: 71.31% vs. 17.68%; ≥ grade 2: 17.83% vs. 4.88%, both P < 0.001). Multivariate analysis identified Planning target volume (PTV) as an independent negative predictor for PFS in the TRT group (P = 0.003). Conclusion Adding TRT to first-line systemic therapy improves survival in metastatic NSCLC. Treatment strategies should be personalized based on molecular subtype and toxicity risk.