Alteration of Prognostic Factors for Patients with Brain Metastases from Lung Cancer Before and After the Introduction of Immune Checkpoint Inhibitors: A Retrospective Single-Institution Study

Background/Objectives: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced lung cancer, but their real-world impact on patients with brain metastases remains insufficiently characterized. This study aimed to compare treatment outcomes before and after the introduction of ICIs and to identify prognostic factors in patients with lung cancer brain metastases. Methods: We retrospectively analyzed 186 patients treated for brain metastases from lung cancer at our institution between 2014 and 2023. Patients were classified into a Pre-ICI group (N = 93, 2014–2018) and a Post-ICI group (N = 93, 2019–2023). Overall survival (OS) was analyzed by Kaplan–Meier method and Cox regression. Baseline factors included age, sex, histology, Charlson–Deyo score, extracranial metastases, radiotherapy, systemic therapy, and neutrophil-to-lymphocyte ratio (NLR, cutoff = 4). Results: Median OS improved significantly in the Post-ICI group compared with the Pre-ICI group (10.9 vs. 4.7 months, p < 0.01). When stratified by systemic therapy, median OS was 4.7 months with conventional chemotherapy, 14.7 months with molecular targeted therapy overall, further prolonged to 25.5 months in the Post-ICI era, and 23.4 months for all patients receiving ICIs. The most notable benefits were observed in patients with squamous cell carcinoma and small cell carcinoma. Patients with NLR ≥ 4 showed shorter OS, but NLR did not remain significant in multivariate analysis. In EGFR-mutant adenocarcinoma, the survival benefit from ICIs was limited. Conclusions: ICIs significantly improved survival in patients with lung cancer brain metastases, particularly those with squamous cell carcinoma or small cell carcinoma. NLR may provide supportive prognostic information, while molecular targeted therapy and ICIs represent major drivers of improved survival in this population.