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

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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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.

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Authors and Affiliations

  1. Medical Oncology Unit 2 - Adult Mesenchymal Tumours and Rare Cancers, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Silvia Stacchiotti MD, Salvatore Provenzano MD, Elena Palassini MD, Michela Libertini MD, Vittoria Colia MD & Paolo G. Casali MD

  2. Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Gianpaolo Dagrada PhD, Tiziana Negri PhD, Silvia Brich PhD & Silvana Pilotti MD

  3. Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy

    Umberto Basso MD & Antonella Brunello MD

  4. Oncology, SS Antonio e Biagio General Hospital, Alessandria, Italy

    Federica Grosso MD

  5. Oncology, Santa Chiara Hospital, Pisa, Italy

    Luca Galli MD

  6. Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Alessandro Gronchi MD

  7. Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy

    Angelo P. Dei Tos MD

  8. Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Flavio Crippa MD

  9. Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Carlo Morosi MD

Authors
  1. Silvia Stacchiotti MD
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  2. Salvatore Provenzano MD
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  3. Gianpaolo Dagrada PhD
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  8. Federica Grosso MD
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  9. Luca Galli MD
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  11. Michela Libertini MD
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  12. Vittoria Colia MD
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  13. Alessandro Gronchi MD
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  14. Angelo P. Dei Tos MD
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  15. Flavio Crippa MD
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  16. Carlo Morosi MD
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  17. Silvana Pilotti MD
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  18. Paolo G. Casali MD
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Corresponding author

Correspondence to Silvia Stacchiotti MD.

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Stacchiotti, S., Provenzano, S., Dagrada, G. et al. Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database. Ann Surg Oncol 23, 2735–2744 (2016). https://doi.org/10.1245/s10434-016-5331-z

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  • DOI: https://doi.org/10.1245/s10434-016-5331-z

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