Incidence, prevalence and treatment of patients with Epithelioid Haemangioendothelioma (EHE) in Canada: A SCanSaRCC & PRO_CARE EHE study

Introduction: Epithelioid Haemangioendothelioma (EHE) is an ultra-rare sarcoma characterized by WWTR1- CAMTA1 or YAP1-TFE3 gene fusions. Clinical behaviour ranges from indolent to aggressive. Due to its rarity, this study aims to describe the presentation, management, and outcomes of EHE patients in Canada. Methods: Data was collected and entered to the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database. Patients of all ages with a documented diagnosis of EHE from Nov 1993 to Jan 2024 were included. Patient demographics, disease characteristics and treatment details were collected using a case report form and summarized using descriptive statistics. Kaplan-Meier method was used to estimate overall survival and event free survival. Cox regression was used to estimate factors influencing survival outcomes. Results: In total, 198 patients were included of which 94 (45.7 %) presented with metastatic disease. The diagnosis was incidental in 61 patients (31 %). The most frequent primary sites were liver (n = 56, 28.3 %), extremities (n = 31, 15.7 %) and lungs (n = 27, 13.6 %). Fusion testing was performed and positive in 43 (22 %) patients. At least one line of systemic therapy was used in 55 (27.8 %) patients with most common agents including sirolimus, pazopanib and paclitaxel. The median EFS was 5.5 years (95 % CI: 3.4–8.5), and the median OS was 8.6 years (95 % CI: 5.4 – 16.5). Liver transplant was performed in seven patients. In multivariate analysis, older age, pleural effusion, ascites, primary lung disease and metastatic disease were associated with poor survival outcomes. Conclusion: This is the largest series of EHE patients describing sequential systemic therapies. The role of systemic therapy in EHE in improving survival remains unclear and prospective studies with comparative arms are needed to add further insight into this chronic disease.