S3139 Survival Outcomes of Gastrointestinal Versus Non-Gastrointestinal Signet Ring Cell Carcinoma With Brain Metastases: A Population-Based Retrospective Analysis

Introduction: Signet ring cell carcinoma (SRCC) is a rare, aggressive adenocarcinoma subtype, typically originating from gastrointestinal (GI) sites. Among patients with colonic SRCC, approximately 11% present with brain metastases at diagnosis, while gastric SRCC involves the brain in approximately 1% of cases. SRCC has a worse prognosis compared to other adenocarcinoma subtypes, and brain metastases further foretell a dismal outcome. Treatment options include surgical resection, stereotactic radiosurgery, whole-brain radiation, and systemic therapy based on primary tumor location. However, targeted therapies are usually ineffective due to the lack of actionable mutations and the low immunogenicity of SRCC. In this study, we aimed to compare survival outcomes between patients with GI-origin SRCC and those with non-GI-origin SRCC presenting with brain metastases. Methods: We conducted a retrospective study using the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2010-2021) to compare survival outcomes in patients with SRCC and brain metastases, stratified by primary site (GI vs non-GI). Patients were identified using International Classification of Diseases code 8490/3. Kaplan-Meier analysis was used to estimate overall survival (OS), and comparisons were made via the log-rank test using GraphPad Prism. Results: A total of 215 patients with SRCC and brain metastases at diagnosis were identified: 122 (56.7%) GI-origin and 93 (43.3%) non-GI. The median time to treatment initiation was 19 days. The cohort was 54% men and 46% women. Among GI-origin cases, 66% originated from the stomach. Median OS for GI-origin SRCC was 3 months, compared to 9 months for non-GI (hazard ratio 1.872; 95% confidence interval 1.373-2.552; P < 0.0001). Conclusion: GI-origin SRCC with brain metastases is associated with significantly poorer survival than non-GI SRCC. These results underscore the aggressive biology of GI SRCC and the need for more effective systemic therapies and precision medicine approaches. Molecular profiling is recommended for all metastatic SRCC to guide therapeutic decision-making. A major limitation is the SEER database’s lack of treatment-specific data, which may influence survival interpretation. Further studies comparing treatment approaches are warranted to optimize survival outcomes in this rare but lethal malignancy.