BACKGROUND: Non-small cell lung cancer (NSCLC) presents the most common type of lung cancer, accounting for 80-85% of cases. Combining immunotherapy with radiotherapy (RT) has emerged as a significant research area in recent years. However, the risk of radiation pneumonitis, especially in lung cancer patients, poses a significant concern. Iodine-125 (I METHODS: Retrospective analysis of 95 patients with driver gene-negative NSCLC who presented to the First Affiliated Hospital of Army Medical University was conducted. Among them, 33 cases in the observation group were treated with I RESULTS: mPFS was not reached in the observation group but 11.8 months [95% confidence interval (CI): 9.743-13.857] in the control group, a statistically significant difference (P<
0.001). The restricted mean survival time (RMST) was 22.2 (95% CI: 18.257-26.101) and 13.8 (95% CI: 11.912-15.718) months in both groups at 31.7 months, PFS was better in the observation group than in the control group. In the observation group, two cases (6.1%) developed grade 3 pneumothorax or hemorrhage, and in the control group, 16 cases (25.8%) developed grade 3 radiation pneumonitis, which was higher in the control group than in the observation group (P=0.02). CONCLUSIONS: Compared to RT in combination with CT and immunotherapy, patients with driver gene-negative NSCLC who received I