Brain Radiotherapy Combined with Immune Checkpoint Inhibitors and Chemotherapy as First-Line Treatment for Advanced Non-Small Cell Lung Cancer with Brain Metastases: A Retrospective Study

Background Brain metastasis (BM) remains a major therapeutic challenge in non-small cell lung cancer (NSCLC) without actionable driver mutations. Radiotherapy combined with immune checkpoint inhibitors (ICIs) may enhance intracranial control through synergistic immune activation. This study evaluated the efficacy of radiotherapy plus immunotherapy and explored prognostic factors influencing outcomes in patients with NSCLC-BM. Methods We retrospectively analyzed 116 patients with measurable, driver-negative NSCLC-BM treated between June 2019 and December 2024. Patients were divided into two groups: ICI plus radiochemotherapy (RT + ICI, n = 56) and ICI plus chemotherapy (ICI, n = 60). Intracranial and systemic objective response rates (iORR, ORR) and progression-free survival (PFS) were compared. Prognostic factors, including the prognostic nutritional index (PNI), were assessed using Cox regression analyses. Results The RT + ICI group achieved a higher iORR (78.6% vs 40.0%, P < 0.001) and longer survival than the ICI group. Median intracranial PFS (iPFS) was 11.8 vs 7.9 months (HR = 0.48, 95% CI 0.30–0.77, P = 0.002), and systemic PFS (sPFS) was 8.9 vs 5.9 months (HR = 0.58, 95% CI 0.38–0.89, P = 0.014). High PNI (≥ 42.15) was independently associated with prolonged iPFS (HR = 8.77, 95% CI 2.91–26.47, P < 0.001) and sPFS (HR = 8.46, 95% CI 3.39–21.10, P < 0.001). Conclusion Radiotherapy combined with immunotherapy provides superior intracranial and systemic efficacy over immunotherapy alone in driver-negative NSCLC-BM. PNI serves as a simple and reliable biomarker for predicting therapeutic benefit and may help guide individualized treatment strategies.