Stereotactic versus whole-brain radiotherapy combined with immunotherapy in driver gene-negative NSCLC with brain metastases: a real-world IPTW analysis

Brain metastases (BMs) are a common and prognostically unfavorable complication of non-small cell lung cancer (NSCLC). Although the combination of immune checkpoint inhibitors (ICIs) with radiotherapy has shown potential in the treatment of BMs, there is a lack of comparative studies specifically contrasting whole-brain radiotherapy (WBRT) versus stereotactic radiotherapy (SRT), each combined with immunotherapy. This study aimed to systematically evaluate the efficacy and safety of WBRT plus immunotherapy (WBRT+I) versus SRT plus immunotherapy (SRT+I) in patients with driver-gene-negative NSCLC accompanied by BMs.

This single-center, real-world retrospective cohort study enrolled patients with driver gene-negative NSCLC and BMs who received their first course of intracranial radiotherapy at Chongqing University Cancer Hospital between January 2018 and June 2024. Inverse Probability of Treatment Weighting (IPTW) was applied to balance baseline variables between the WBRT+I and SRT+I groups. Survival outcomes were evaluated using Kaplan-Meier analysis and Cox regression. The primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS). Secondary endpoints included the intracranial objective response rate (iORR), intracranial disease control rate (iDCR), and safety profile.

In this real-world cohort of 158 patients with driver gene-negative NSCLC with BMs, SRT+I demonstrated superior survival outcomes compared to WBRT+I. After IPTW adjustment, SRT+I was associated with significantly prolonged median overall survival (29.3 vs. 19.9 months, P = 0.034) and intracranial progression-free survival (14.7 vs. 9.4 months, P = 0.038). These advantages remained consistent in the subgroup with ≤4 BMs. Immunotherapy administered after radiotherapy yielded superior survival compared to the reverse sequence. The SRT+I group also achieved a higher intracranial objective response rate (78.6% vs. 61.5%) and disease control rate (95.0% vs. 88.5%), with a lower incidence of documented radiation-induced brain injury (3.75% vs. 10.26%) and no grade ≥3 immune-related adverse events.

In driver-gene-negative NSCLC patients with BMs, SRT+I demonstrates superior survival and intracranial disease control compared to WBRT+I, particularly in those with limited BMs. These findings provide high-level evidence for optimizing individualized clinical strategies.