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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2016

01-09-2016 | Bone and Soft Tissue Sarcomas

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

Authors: Silvia Stacchiotti, MD, Salvatore Provenzano, MD, Gianpaolo Dagrada, PhD, Tiziana Negri, PhD, Silvia Brich, PhD, Umberto Basso, MD, Antonella Brunello, MD, Federica Grosso, MD, Luca Galli, MD, Elena Palassini, MD, Michela Libertini, MD, Vittoria Colia, MD, Alessandro Gronchi, MD, Angelo P. Dei Tos, MD, Flavio Crippa, MD, Carlo Morosi, MD, Silvana Pilotti, MD, Paolo G. Casali, MD

Published in: Annals of Surgical Oncology | Issue 9/2016

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Abstract

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.
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Metadata
Title
Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database
Authors
Silvia Stacchiotti, MD
Salvatore Provenzano, MD
Gianpaolo Dagrada, PhD
Tiziana Negri, PhD
Silvia Brich, PhD
Umberto Basso, MD
Antonella Brunello, MD
Federica Grosso, MD
Luca Galli, MD
Elena Palassini, MD
Michela Libertini, MD
Vittoria Colia, MD
Alessandro Gronchi, MD
Angelo P. Dei Tos, MD
Flavio Crippa, MD
Carlo Morosi, MD
Silvana Pilotti, MD
Paolo G. Casali, MD
Publication date
01-09-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5331-z

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