Clinicopathologic determinants of survival of hepatoid adenocarcinoma of the stomach: Analysis of a pooled database.

Abstract

e16018 Background: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer characterized by histological and functional features that resemble hepatocellular carcinoma, including the production of alpha-fetoprotein (AFP). Due to its rarity, there is a limited understanding of its clinical behavior and optimal management strategies. This exploratory analysis aims to evaluate an HAS database to identify demographic patterns, therapeutic approaches, and prognostic factors that may inform future research and guide the clinical management of this rare malignancy. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of cases that satisfy the diagnostic criteria for HAS. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 141 patients with confirmed HAS were identified. The median age was 63, with a male preponderance (M:F 2.7). The median tumor size was 5.5 cm, and the median AFP level was 2000 ng/ml, with 12% of the cases being non-secretors. Thirty-two percent were proximal. 24% mid, and 44% distal. Fifty-six percent were metastatic. The most common metastatic sites were the liver (91%), lungs (23%) and peritoneum (14%). The median OS was 20 months. Males had a better OS (24 vs. 14 months, p = 0.004). Stage IV (M+) had worse survival compared to N0/1M0 and N3M0 (12 vs. 27 vs. 28 months; p = 0.001), respectively. Pulmonary (p = 0.0002) and peritoneal (p = 0.0001) metastases were associated with worse survival. In non-metastatic stages (TxNxM0), the addition of chemotherapy (CT) to surgical resection (S) was associated with a survival advantage at 24 months (p = 0.04). In M+ stages, compared to no treatment, CT, S, and S+CT were superior in increasing order, with a median OS of 1.3, 8, 18, and 22 months, respectively (p = 0.0001). Platinum-based regimens were superior to non-platinum containing regimens, with a median OS of 16 vs. 4 months. Age, sex, gastric location, size, and AFP levels did not impact OS. Conclusions: This pooled analysis highlights key prognostic factors, which include metastatic burden and sites, with pulmonary and peritoneal metastases associated with worse outcomes. In non-metastatic stages, combining chemotherapy with surgical resection significantly improves survival. For metastatic disease, multimodal therapy, particularly surgical resection, when feasible, combined with chemotherapy, offers the best survival outcomes. Platinum-based regimens show superior efficacy in advanced stages. These findings underscore the need for tailored therapeutic approaches and further research to optimize outcomes for this rare malignancy.