Department of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy.
Unit of Clinical Epidemiology and Trial Organization, IRCCS Foundation National Cancer Institute, Milan, Italy.
Cancer. 2021 Feb 15;127(4):569-576. doi: 10.1002/cncr.33247. Epub 2020 Oct 27.
The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network.
From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method.
All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction.
The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.
本研究旨在报告在意大利罕见癌症网络中接受西罗莫司治疗的上皮样血管内皮细胞瘤（EHE）患者的回顾性系列病例。
自 2005 年 1 月起，38 例晚期 EHE 成人患者接受了连续剂量的西罗莫司治疗，每日 5mg，直至出现毒性或疾病进展。治疗前 6 个月需要疾病进展。每个病理诊断均进行了复查。根据血浆水平调整西罗莫司的日剂量。局部研究者使用实体瘤反应评估标准 1.1（RECIST）回顾性评估反应。使用 Kaplan-Meier 方法估计生存情况。
所有 38 例患者（WW 结构域包含转录调节因子 1[WWTR1]阳性，n=37；转录因子 E3[TFE3]阳性，n=1）在开始使用西罗莫司前均有疾病进展（基线时，38 例患者中有 13 例存在浆膜腔积液和全身症状）。37 例患者可评估反应（1 例早期中断）。最佳 RECIST 反应为 4 例患者部分缓解（10.8%），28 例患者病情稳定（75.7%），5 例患者疾病进展（13.5%）。在中位随访 41.5 个月（四分位距[IQR]，23.9-56.8 个月）时，中位 PFS 为 13 个月（95%CI，3.7 个月至无法估计[NE]），中位 OS 为 18.8 个月（95%CI，10.6 个月至 NE）。基线时存在浆膜腔积液的患者，中位 PFS 为 4.8 个月（IQR，3.5-11.7 个月），中位 OS 为 10.6 个月（IQR，5.1-13.0 个月），而无浆膜腔积液的患者分别为 47.8 个月（IQR，11.4 个月至 NE）和 47.8 个月（IQR，15.7 个月至 NE）。总体而言，西罗莫司耐受性良好，10 例患者报告出现不规则月经/卵巢功能障碍。
目前的结果证实，西罗莫司在 EHE 中具有活性，可使大多数无浆膜腔积液的患者病情稳定延长。浆膜腔积液被证实为预后不良的标志，与生存期短相关，而西罗莫司在该亚组中的活性有限。
