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Annals of Surgical Oncology

, Volume 23, Issue 9, pp 2735–2744 | Cite as

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

  • Silvia Stacchiotti
  • Salvatore Provenzano
  • Gianpaolo 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 G. Casali
Bone and Soft Tissue Sarcomas

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.

Keywords

Sirolimus Angiosarcoma Pazopanib Clinical Benefit Rate Epithelioid Hemangioendothelioma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank the following pathologists who kindly contributed case material: L. Ambrosiani, Anatomia ed Istologia Patologica e Citodiagnostica, Ospedale Valduce, Como, Italy; M. Paulli, Medicina di Laboratorio-Anatomia Patologica, Policlinico San Matteo, Pavia, Italy; and C. Cattaneo, Anatomia Patologica, Azienda Ospedaliera di Desio e Vimercate, Vimercate, Italy.

Disclosures

Silvia Stacchiotti, Vittoria Colia, Michela Libertini, and Elena Palassini: Pfizer, research funding. Alessandro Gronchi: Pfizer, advisory (compensated). Angelo P. Dei Tos: Pfizer, honoraria. Paolo G. Casali: Pfizer, advisory (compensated) and research funding. Salvatore Provenzano, Gianpaolo Dagrada, Tiziana Negri, Silvia Brich, Umberto Basso, Antonella Brunello, Federica Grosso, Luca Galli, Flavio Crippa, Carlo Morosi, and Silvana Pilotti have no conflicts of interest to declare.

Supplementary material

10434_2016_5331_MOESM1_ESM.docx (33 kb)
Supplementary material 1 (DOCX 32 kb)
10434_2016_5331_MOESM2_ESM.tif (314 kb)
Supplementary material 2 (TIFF 314 kb)

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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Silvia Stacchiotti
    • 1
  • Salvatore Provenzano
    • 1
  • Gianpaolo Dagrada
    • 2
  • Tiziana Negri
    • 2
  • Silvia Brich
    • 2
  • Umberto Basso
    • 3
  • Antonella Brunello
    • 3
  • Federica Grosso
    • 4
  • Luca Galli
    • 5
  • Elena Palassini
    • 1
  • Michela Libertini
    • 1
  • Vittoria Colia
    • 1
  • Alessandro Gronchi
    • 6
  • Angelo P. Dei Tos
    • 7
  • Flavio Crippa
    • 8
  • Carlo Morosi
    • 9
  • Silvana Pilotti
    • 2
  • Paolo G. Casali
    • 1
  1. 1.Medical Oncology Unit 2 - Adult Mesenchymal Tumours and Rare Cancers, Department of Cancer MedicineFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  2. 2.Experimental Molecular Pathology Unit, Department of PathologyFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  3. 3.Medical Oncology Unit 1, Department of Clinical and Experimental OncologyIstituto Oncologico Veneto IOV IRCCSPaduaItaly
  4. 4.OncologySS Antonio e Biagio General HospitalAlessandriaItaly
  5. 5.OncologySanta Chiara HospitalPisaItaly
  6. 6.Department of SurgeryFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  7. 7.Department of Anatomic PathologyGeneral Hospital of TrevisoTrevisoItaly
  8. 8.Department of Nuclear MedicineFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  9. 9.Department of RadiologyFondazione IRCCS Istituto Nazionale TumoriMilanItaly

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