Survival outcomes and molecular predictors in small cell lung cancer with brain metastases receiving immunotherapy

To evaluate the real-world efficacy of chemoimmunotherapy combined with brain radiotherapy and to explore prognostic biomarkers in patients with small cell lung cancer (SCLC) and brain metastases (BM).

We retrospectively analyzed 133 consecutive patients with de novo SCLC-BM. Patients were categorized into a chemotherapy-only cohort (n = 54) and a chemoimmunotherapy cohort (n = 79). Survival outcomes were assessed. Exploratory analyses included serum markers (NSE, CEA) and tissue molecular subtypes (SCLC-A/N/P/TN) identified via multiplex immunofluorescence.

Chemoimmunotherapy was significantly associated with prolonged median progression-free survival (6.1 vs. 5.1 months, P = 0.034) and overall survival (10.2 vs. 9.0 months, P = 0.019) compared to chemotherapy alone. Time-dependent multivariate analysis confirmed that both chemoimmunotherapy (adjusted HR = 0.65, P = 0.032) and brain radiotherapy (time-dependent HR = 0.63, P = 0.040) were independent protective factors for overall survival. Notably, the longest median overall survival (15.2 months) was observed in patients receiving the combination of chemoimmunotherapy and brain radiotherapy. In exploratory biomarker analyses, high baseline NSE coupled with low CEA levels correlated with poor prognosis (HR = 6.47). Furthermore, distinct molecular heterogeneity was observed; SCLC-N and SCLC-P subtypes were associated with significantly inferior survival compared to SCLC-A and SCLC-TN phenotypes.

First-line atezolizumab plus chemotherapy is associated with favorable survival outcomes in patients with SCLC brain metastases, and the longest survival was observed when combined with brain radiotherapy. Additionally, exploratory analyses suggest that high neuroendocrine burden and specific molecular subtypes (SCLC-N/P) may serve as potential prognostic biomarkers, warranting prospective validation.