Brain radiotherapy added to first-line immunochemotherapy improves survival in patients with treatment-naïve, driver-negative lung adenocarcinoma and synchronous brain metastases.

[OBJECTIVE] The optimal integration of brain radiotherapy with first-line immunochemotherapy for treatment-naïve, driver-negative lung adenocarcinoma patients with synchronous brain metastases remains unclear. This study assessed the efficacy and safety of this combined strategy.

[METHODOLOGY] In this retrospective cohort, 172 eligible patients were divided into two groups: the Combination group (immunochemotherapy plus brain radiotherapy, n=86) and the Systemic therapy group (immunochemotherapy alone, n=86). The primary endpoint was overall survival (OS); secondary endpoints included intracranial progression-free survival (iPFS), progression-free survival (PFS), intracranial/extracranial objective response rates (iORR/eORR) and safety.

[RESULTS] After a median follow-up of 36.5 months, the Combination group showed significantly longer median OS (23.5 vs. 17.5 months; HR = 0.729, 95%CI:0.538-0.988, P = 0.036) and iPFS (13.6 vs. 7.7 months; HR = 0.699, 95%CI:0.515-0.947, P = 0.017), while unadjusted PFS showed no statistical difference (P = 0.245). iORR was higher in the Combination group (66.3% vs. 46.5%, P = 0.009), with comparable eORR between groups. Multivariate analysis verified brain radiotherapy as an independent favorable factor for OS and iPFS, with consistent benefits across subgroups. Safety profiles were manageable, with no elevated severe immune-related toxicities.

[CONCLUSION] For this patient population, adding brain radiotherapy to first-line immunochemotherapy significantly improves OS and intracranial disease control, without impairing systemic efficacy or increasing severe toxicity, supporting its clinical consideration.