Pimenta Erica M, Goyal Anirudh, Farber Orly N, Lilley Elizabeth, Shyn Paul B, Wang Jiping, Wagner Michael J
Sarcoma and Bone Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Curr Treat Options Oncol. 2025 May 14. doi: 10.1007/s11864-025-01328-2.
Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma with a paucity of data on best practices for management. Pathogenic translocations involving the YAP or TAZ genes lead to constitutive activation of TEAD and TEAD-associated pathways. As our understanding of the molecular drivers of EHE has advanced, investigational treatment strategies have shifted away from cytotoxic chemotherapy toward more targeted approaches. This review focuses on the historical context and evolving landscape of systemic therapies for patients with EHE. For newly diagnosed patients, we recommend consultation at a high-volume sarcoma center whenever possible. If the disease is localized and resectable, surgical excision by a sarcoma-focused surgical oncologist is preferred. When the disease is unresectable, we first assess for disease progression to determine whether active surveillance is appropriate. Some patients may experience indolent, asymptomatic disease for years-or even decades-without requiring intervention. In patients with progressive or symptomatic unresectable disease, systemic therapy is warranted. Setting realistic expectations about the goals of treatment is essential, as no current systemic therapies reliably reduce tumor burden. However, molecular profiling and ongoing correlative studies from clinical trials may soon identify more effective therapeutic targets. For this reason, we encourage referral to centers that routinely perform molecular profiling and offer clinical trials with eligibility criteria for EHE, even to be considered as a first-line approach. Outside of a clinical trial, cytotoxic chemotherapy remains the frontline standard of care for patients who require systemic treatment. Importantly, treatment decisions must incorporate patient preferences and recognition that symptomatic improvement alone can be a meaningful outcome for preserving quality of life.
上皮样血管内皮瘤（EHE）是一种极为罕见的肉瘤，关于其最佳治疗方法的数据匮乏。涉及YAP或TAZ基因的致病性易位会导致TEAD和TEAD相关通路的组成性激活。随着我们对EHE分子驱动因素的认识不断深入，研究性治疗策略已从细胞毒性化疗转向更具靶向性的方法。本综述重点关注EHE患者全身治疗的历史背景和不断演变的格局。对于新诊断的患者，我们建议尽可能在大型肉瘤中心进行会诊。如果疾病局限且可切除，由专注于肉瘤的外科肿瘤学家进行手术切除是首选。当疾病不可切除时，我们首先评估疾病进展以确定主动监测是否合适。一些患者可能多年甚至数十年患有惰性、无症状疾病而无需干预。对于进展性或有症状的不可切除疾病患者，有必要进行全身治疗。对治疗目标设定现实的期望至关重要，因为目前尚无可靠降低肿瘤负荷的全身治疗方法。然而，分子谱分析和来自临床试验的正在进行的相关性研究可能很快会确定更有效的治疗靶点。因此，我们鼓励转诊至常规进行分子谱分析并提供符合EHE纳入标准的临床试验的中心，甚至可将其视为一线治疗方法。在临床试验之外，细胞毒性化疗仍然是需要全身治疗的患者的一线标准治疗方法。重要的是，治疗决策必须纳入患者的偏好，并认识到仅症状改善就可能是维持生活质量的有意义结果。
