E. Dogeas1, A. E. Mokdad1, M. Porembka1, S. Wang1, A. Yopp1, P. Polanco1, J. Mansour1, R. Minter1, M. A. Choti1, M. M. Augustine1 1University Of Texas Southwestern Medical Center,Surgical Oncology,Dallas, TX, USA
Introduction: Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary liver vascular malignancies that remain poorly understood. We sought to identify factors predicting survival after surgical intervention using a large national database in an effort to guide management.
Methods: In a retrospective analysis of the National Cancer Database (2004-2013) patients with a diagnosis of AS and HEHE were identified. Clinicopathologic factors were extracted. The Mann-Whitney U and chi-squared tests were used to compare the two disease groups. Overall survival (OS) was estimated with the Kaplan-Meier method and the Cox proportional hazards model was used to identify predictors of survival.
Results: 137,051 primary liver malignancies were captured in the NCDB. AS was diagnosed in 390 (0.3%) and HEHE in 216 (0.1%) patients. AS patients were older (59 vs 46 years, p<0.001), male (64% vs 43%, p<0.001) and presented with larger tumors (7.9 vs 3.8 cm, p<0.001) that more commonly exhibited poor differentiation (25% vs 2%, p<0.001). Only 16% of AS and 36% of HEHE patients underwent surgery(p<0.001). The median OS in the entire cohort was 5 months, with AS patients exhibiting worse prognosis (5-year OS: 5% vs 51%, p<0.001).
Within the surgically-managed cohort (n=142), AS patients tended to be older (59 vs 46 years. p<0.001) and exhibited larger (6.5 vs 3.8 cm, p<0.001) and more poorly differentiated tumors (34% vs 5%, p<0.001). Surgical interventions, including ablation, minor and major hepatectomy, and liver transplantation were similar between the two histologic groups (p=0.128). Negative-margin resection was achieved in ~70% of both groups. The median OS for surgically-managed patients was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (p<0.001). Tumor biology strongly impacted OS, with AS histology conferring a Hazard Ratio (HR) of 3.61 (1.55-8.42), moderate/poor tumor differentiation a HR of 3.86 (1.03-14.46) and tumor size a HR of 1.01 (1.00-1.01). The presence of metastatic disease in the surgically managed cohort, HR: 5.22 (2.01-13.57), and involved surgical margins, HR: 3.87 (1.59-9.42), were independently associated with worse survival. Finally, patient age was negatively associated with OS, HR: 1.04 (1.01-1.07), while the type of operation was not (p=0.894).
Conclusion: In this national cohort, we identified factors that influence patient outcomes in surgically managed, primary hepatic vascular malignancies. AS histology, tumor differentiation and tumor size were strongly associated with survival. Residual tumor burden after surgical resection, in the form of positive surgical margins and the presence of metastasis, were negatively associated with survival. Despite attempts at curative-intent surgery for hepatic vascular malignancies, tumor biology impacts survival, emphasizing the need for effective forms of adjunctive systemic therapies for this group of malignancies.