Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database

Silvia Stacchiotti, S. Provenzano, Gian Paolo Dagrada, Tiziana Negri, Silvia Brich, Umberto Basso, Antonella Brunello, Federica Grosso, Luca Galli, Elena Palassini, Michela Libertini, Vittoria Colia, Alessandro Gronchi, Angelo P. Dei Tos, Flavio Crippa, Carlo Morosi, Silvana Pilotti, Paolo Giovanni Casali

Research output: Contribution to journalArticlepeer-review


Background: The aim of this study was to report on sirolimus activity in a series of patients with hemangioendothelioma (HE) treated at the National Cancer Institute, Milan (Istituto Nazionale Tumori; INT) and within the Italian Rare Cancer Network (“Rete Tumori Rari”; RTR). Methods: We retrospectively reviewed patients with advanced and progressing epithelioid hemangioendothelioma (EHE) treated with sirolimus at the INT and/or within the RTR. Pathologic review and molecular analysis for WWTR1 rearrangement were performed. Sirolimus was administered until unacceptable toxicity or progression, with the dose being adjusted to reach target plasma levels of 15–20 ng/dL. Responses were assessed using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Results: Since 2005, 18 patients (17 EHE, 1 retiform HE; 1 locally advanced, 17 metastatic; WWTR1 rearrangement: 16) have been identified, with 17/18 patients being evaluable for response. Mean sirolimus daily dose was 4.5 mg. According to RECIST, best responses in EHE were 1 partial response (PR), 12 stable disease (SD), and 3 progressive disease (PD); the patient with retiform HE also achieved a PR, lasting >2 years. Four patients with a reversed interval progression on interruption were observed. Median overall survival was 16 months, and median progression-free survival was 12 months (range 1–45), with four patients progression-free at 24 months. The clinical benefit (complete response [CR] + PR + SD >6 months) was 56 %. Seven patients receiving sirolimus experienced an increase in pleural/peritoneal effusion plus worsening of tumor-related symptoms; six of these patients died within 1–8 months from evidence of effusion progression, while a RECIST PD was assessed in two of seven patients. Conclusions: A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients. Most patients with pleural effusion did not benefit from sirolimus and had a poor outcome.

Original languageEnglish
Pages (from-to)2735-2744
Number of pages10
JournalAnnals of Surgical Oncology
Issue number9
Publication statusPublished - Sep 2016

ASJC Scopus subject areas

  • Surgery
  • Oncology


Dive into the research topics of 'Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database'. Together they form a unique fingerprint.

Cite this