Effects of multimodal local therapy on survival in gastric cancer leptomeningeal metastases.

Abstract

e14022 Background: Leptomeningeal metastasis (LM) from gastric cancer represents a terminal condition with poor prognosis, where the efficacy of systemic therapy is limited by the blood-brain barrier. While local strategies such as whole-brain radiotherapy (WBRT), intrathecal (IT) chemotherapy, and surgical decompression (e.g., VP shunt, EVD) are utilized, the clinical impact of combining these modalities remains under-investigated. We evaluated the real-world safety and survival outcomes of this multimodal strategy. Methods: We analyzed 15 patients with gastric cancer LM treated at Guangdong Sanjiu Brain Hospital. Treatment regimens integrated systemic therapy with distinct local therapeutic modalities and their combinations, including WBRT, IT chemotherapy, and neurosurgical interventions (Ommaya reservoir, VP shunt, or EVD). The primary endpoint was overall survival (OS) from the diagnosis of LM. Survival outcomes were assessed using Kaplan-Meier methods and Log-rank tests. Safety was graded according to CTCAE v5.0. Results: The median OS for the entire cohort was 6.9 weeks. The multimodal regimen demonstrated a favorable safety profile; no Grade 3-4 adverse events were recorded. Toxicities were predominantly Grade 1-2 hematologic. Device-related complications occurred in 13.3% of patients and were manageable. Analysis of specific modalities revealed significant survival benefits. The addition of WBRT conferred a highly significant survival extension compared to non-WBRT regimens (median OS: 7.7 vs. 3.5 weeks; Log-rank P = 0.0024). Similarly, patients receiving IT chemotherapy exhibited superior survival compared to the non-IT group (8.7 vs. 4.6 weeks; P = 0.045). The "Combined Local Therapy" cohort (comprising Surgery [VP shunt/EVD] + WBRT + IT) showed a strong trend toward improved survival compared to limited local therapy (9.9 vs. 5.4 weeks; P = 0.054). Furthermore, baseline CSF-CEA <5 ng/ml was identified as a robust predictor of prolonged survival (24.6 vs. 6.0 weeks; P = 0.0299). Conclusions: Comprehensive multimodal therapy is feasible and safe for patients with gastric cancer LM, showing zero severe toxicity. The significant survival benefit observed with WBRT and IT chemotherapy suggests that restoring CSF flow and reducing intracranial tumor burden are critical components of management. The combination of surgical intervention (VP shunt/EVD), WBRT, and IT chemotherapy offers a promising therapeutic strategy that warrants further validation.