Efficacy of radiotherapy combined with immunotherapy in driver gene-negative non–small cell lung cancer with brain metastases: A single-center retrospective analysis

ObjectiveTo evaluate the efficacy and safety of radiotherapy plus immune checkpoint inhibitors versus radiotherapy plus chemotherapy in driver gene-negative patients with non-small cell lung cancer and brain metastases.MethodsThis single-center retrospective cohort study (Strengthening the Reporting of Observational Studies in Epidemiology-compliant) enrolled 60 consecutive driver gene-negative patients with non-small cell lung cancer and brain metastases (29 radiotherapy plus immune checkpoint inhibitors, 31 radiotherapy plus chemotherapy) treated between June 2018 and December 2023, with follow-up until July 2025. Survival, tumor response, and immune-related adverse events were analyzed using Kaplan-Meier methods, Cox models, and chi-square tests. The study was approved by the Institutional Review Board and used deidentified data.ResultsRadiotherapy plus immune checkpoint inhibitors significantly prolonged median overall survival (586 vs. 509 days, p = 0.0208) and progression-free survival (494 vs. 383 days, p = 0.0127) as well as improved objective response rate (34.48% vs. 19.35%, p = 0.0394) and disease control rate (75.86% vs. 51.61%, p = 0.0265) compared with radiotherapy plus chemotherapy. Favorable prognostic factors included age <60 years, Eastern Cooperative Oncology Group Performance Status <2, programmed death-ligand 1 tumor proportion score ≥50%, and absence of extracranial metastasis. Radiotherapy plus immune checkpoint inhibitors-related immune-related adverse events (24.14%) were mostly grades 1-2, with no grade ≥4 events.ConclusionsRadiotherapy plus immune checkpoint inhibitors may confer survival benefits and favorable safety in driver gene-negative patients with non-small cell lung cancer and brain metastases. However, caution is warranted in interpreting these findings, which require validation in large-scale prospective studies.