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.

Abstract

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 ICI 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: Radiotherapy combined with ICI plus chemotherapy (RT + ICI, n = 56) and ICI plus chemotherapy (ICI, n = 60). Intracranial and systemic objective response rates (iORR, sORR) and progression-free survival (iPFS, sPFS) were analyzed. Prognostic factors, including the prognostic nutritional index (PNI), were assessed using Cox regression analyses.

Results: Compared with the ICI group, the RT + ICI group demonstrated a significantly higher iORR (78.6% vs 40.0%, P < 0.001) and significantly longer median iPFS (11.8 vs 7.9 months; hazard ratio [HR] = 0.48, 95% confidence intervals [CI] 0.30-0.77, P = 0.002), and sPFS (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 immunochemotherapy was associated with improved intracranial and systemic outcomes compared to immunochemotherapy alone in patients with driver-negative NSCLC-BM. Additionally, PNI shows potential as a useful biomarker for predicting therapeutic outcomes.