Effect of dose-escalated WBRT on survival in NSCLC leptomeningeal metastases: A multimodal analysis of local and systemic therapies.

Abstract

e14021 Background: Leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) carry a dismal prognosis. Modern management combines systemic therapies (targeted therapy [TT], chemotherapy, and immunotherapy) with local therapies (whole-brain radiotherapy [WBRT] and intrathecal chemotherapy [IT]). While most centers use 30Gy/10 fractions WBRT, whether dose escalation provides additive benefit when combined with effective systemic therapies remains unclear. We evaluated survival outcomes across WBRT fractionation regimens in the context of contemporary multimodal local and systemic treatment strategies. Methods: We performed a retrospective analysis of 160 NSCLC patients with LM treated with WBRT at Sanjiu Brain Hospital between December 2019 and March 2024. Patients received one of three WBRT regimens: 30Gy/10 fractions, 36Gy/18 fractions, or 40Gy/20 fractions. Systemic therapies included TT, chemotherapy, immunotherapy, and VEGF inhibitors. Local therapies included WBRT and IT. Univariate and multivariate Cox proportional hazards models assessed the independent impact of WBRT dose, along with clinical factors including age, sex, mutation status, IT, and systemic therapy, on overall survival. The primary endpoint was overall survival from the time of WBRT completion. Results: Among 160 patients (82 males, 78 females), 91% received systemic TT (predominantly EGFR/ALK inhibitors) and 73% received IT, reflecting modern practice patterns. 13 (8%) received 30Gy/10f, 56 (35%) received 36Gy/18f, and 91 (57%) received 40Gy/20f. With a median follow-up of 259 days, 119 deaths occurred. Median OS was 325 days (95% CI: 258-387) for 40Gy/20f vs. 298 days (95% CI: 242-607) for 36Gy/18f vs. 120 days (95% CI: 80-NA) for 30Gy/10f (log-rank p=0.011). Both systemic and local therapies demonstrated survival benefit: TT (325 vs. 173 days without TT; HR 0.39, 95% CI: 0.21-0.70, p=0.002) and IT (346 vs. 199 days without IT; HR 0.62, 95% CI: 0.42-0.92, p=0.016). After adjusting for all treatment modalities, each component retained independent significance: 36Gy/18f WBRT (HR 0.29, 95% CI: 0.15-0.57, p<0.001), 40Gy/20f WBRT (HR 0.37, 95% CI: 0.20-0.70, p=0.002), TT (HR 0.35, 95% CI: 0.19-0.65, p<0.001), and IT (HR 0.57, 95% CI: 0.38-0.84, p=0.005). Conclusions: In NSCLC patients with LM, optimal outcomes require integration of both systemic and local therapies. Dose-escalated WBRT (36Gy/18f and 40Gy/20f) provides an independent survival benefit beyond standard 30Gy/10f, even in patients receiving effective systemic TT. Both local therapies (higher-dose WBRT and IT) and systemic therapy (TT) independently contribute to survival, suggesting comprehensive multimodal strategies incorporating all three modalities. These findings warrant prospective validation to optimize integrated treatment approaches in this poor-prognosis population.