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      Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

      review-article
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      ESMO Open
      Elsevier
      sarcoma, epithelioid hemangioendothelioma, diagnosis, treatment, management, guidelines

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          Abstract

          Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

          Highlights

          • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE).

          • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN.

          • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.

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          Most cited references96

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          The Hippo pathway and human cancer.

          The Hippo pathway controls organ size in diverse species, whereas pathway deregulation can induce tumours in model organisms and occurs in a broad range of human carcinomas, including lung, colorectal, ovarian and liver cancer. Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, with only the upstream pathway gene neurofibromin 2 (NF2) recognized as a bona fide tumour suppressor gene. In this Review, we appraise the evidence for the Hippo pathway as a cancer signalling network, and discuss cancer-relevant biological functions, potential mechanisms by which Hippo pathway activity is altered in cancer and emerging therapeutic strategies.
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            Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update

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              Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

              Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                ESMO Open
                ESMO Open
                ESMO Open
                Elsevier
                2059-7029
                02 June 2021
                June 2021
                02 June 2021
                : 6
                : 3
                : 100170
                Affiliations
                [1 ]Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [2 ]The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
                [3 ]Department of Radiology, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
                [4 ]Radiology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [5 ]Palliative Care Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [6 ]Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA
                [7 ]Medical Oncology Department, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
                [8 ]Department of Radiation Oncology, Dana-Farber Cancer Center/Brigham and Women's Hospital, Boston, USA
                [9 ]Department of Medical Oncology, West German Cancer Center, Sarcoma Center, University of Duisburg-Essen, University Hospital, Essen, Germany
                [10 ]Orthopaedic Department, Regina Elena National Cancer Institute, Rome, Italy
                [11 ]Klinikum Stuttgart – Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Stuttgart Cancer Center, Pädiatrische Onkologie, Hämatologie, Immunologie, Stuttgart, Germany
                [12 ]Department of Medical Oncology, Centre Leon Berard, Université Claude Bernard Lyon, Unicancer, Lyon, France
                [13 ]Department of Surgical Oncology, Institut Curie, Université Paris Sciences et Lettres, Paris, France
                [14 ]Nordix, Athens, Greece
                [15 ]Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
                [16 ]Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
                [17 ]Medical University Vienna & General Hospital Department of Internal Medicine 1/Oncology, Vienna, Austria
                [18 ]Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [19 ]Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
                [20 ]Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain
                [21 ]The EHE Foundation, Wisconsin, USA
                [22 ]Department of Oncology, Skane University Hospital and Lund University, Lund, Sweden
                [23 ]Orthopaedic Service, Musculoskeletal Oncology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
                [24 ]Medical Oncology Division, P.A. Herzen Cancer Research Institute, Moscow, Russian Federation
                [25 ]Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
                [26 ]Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [27 ]Department of Pathology Brigham & Women's Hospital, Boston, USA
                [28 ]University of Barcelona and Genitourinary Cancer and Sarcoma Unit Institut Català d'Oncologia, Hospitalet, Barcelona, Spain
                [29 ]Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
                [30 ]University of Toronto and Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
                [31 ]Department of Surgery, Centre Leon Berard, Lyon, France
                [32 ]Division of Medical Oncology, Candiolo Cancer Institute, FPO – IRCCS, Candiolo, Italy
                [33 ]NUY Langone Medical Center, New York, USA
                [34 ]Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands
                [35 ]Department of Radiotherapy, the Leiden University Medical Center, Leiden, the Netherlands
                [36 ]Group of Advanced Therapies and Biomarkers in Sarcoma, Institute of Biomedicine of Seville (IBIS, HUVR, CSIC, Universidad de Sevilla), Seville, Spain
                [37 ]Division of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Heidelberg, Germany
                [38 ]Division of Molecular Pathology, The Institute of Cancer Research, London, UK
                [39 ]Department of Oncology, Helsinki University Hospital & Helsinki University, Helsinki, Finland
                [40 ]Department of Cancer, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
                [41 ]Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
                [42 ]University of Heidelberg, Mannheim University Medical Center, Sarcoma Unit, Mannheim, Germany
                [43 ]Musculoskeletal Oncology and Rehabilitation Medicine, Rare Cancer Center National Cancer Center Hospital, Tokyo, Japan
                [44 ]International Department, Gustave Roussy, Villejuif, France
                [45 ]UCLH - University College London Hospitals NHS Foundation Trust, London, UK
                [46 ]Department of Orthopaedics and Trauma Medical University Graz, Graz, Austria
                [47 ]Chair of Trustees of the EHE Rare Cancer Charity (UK), Charity number 1162472
                [48 ]Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain
                [49 ]Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain
                [50 ]Unit of Soft Tissue and Bone Oncology, Division of Oncology, Tel-Aviv Medical Center affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
                [51 ]Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
                [52 ]Department of Clinical Epidemiology and Trial Organisation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [53 ]Sarcoma Group, Gustave Roussy, Villejuif, France
                [54 ]University of Pittsburgh Medical Center, Thomas Starzl Transplant Institute, Pittsburgh, USA
                [55 ]Oncology, CHUV Lausanne, Lausanne, Switzerland
                [56 ]Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
                [57 ]Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
                [58 ]Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
                [59 ]Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA
                [60 ]Department of Medical Oncology, Institut Curie, Paris, France
                [61 ]Department of Surgery, Brigham and Women's Hospital, Boston, USA
                [62 ]Center for Sarcoma and Bone Oncology, Harvard Medical School, Boston, USA
                [63 ]Dana Farber Cancer Center, Harvard Medical School, Boston, USA
                [64 ]Princess Margaret Cancer Centre and Sinai Healthcare System & Faculty of Medicine, University of Toronto, Toronto, Canada
                [65 ]Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care, Berlin, Germany
                [66 ]Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, USA
                [67 ]Maria Sklodowska-Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland
                [68 ]Aarhus University Hospital, Aarhus, Denmark
                [69 ]Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [70 ]Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
                [71 ]Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy
                [72 ]Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
                [73 ]Leuven Cancer Institute, Leuven, Belgium
                [74 ]Department of Surgery, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK
                [75 ]University College London Hospital, London, UK
                [76 ]Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA
                [77 ]Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [78 ]Palliative Care, The Royal Marsden Hospital and The Institute of Cancer Research London
                [79 ]Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
                [80 ]Department of Orthopedic Surgery Bone and Soft Tissue Tumor Unit, Leiden University Medical Center, Leiden, The Netherlands
                [81 ]Sarcoma and Melanoma Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands
                [82 ]Co-Chair of Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany & Chairman of the Dutch organisation for sarcoma patients (Patiëntenplatform Sarcomen), Guest researcher at Leiden University (Leiden Institute for Advanced Computer Science), Leiden University, Leiden, The Netherlands
                [83 ]Chair of the Board of Directors of Sarcoma Patients EuroNet (SPAEN), Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany
                [84 ]The Royal Marsden NHS Foundation Trust, London, UK
                [85 ]Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
                [86 ]Department of Supportive Care, Princess Margaret Cancer Centre and Division of Palliative Medicine, Department of Medicine, University of Toronto, Toronto, Canada
                Author notes
                [] Correspondence to: Dr. Silvia Stacchiotti, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, Milan, Italy. Tel: +39-0223902803 silvia.stacchiotti@ 123456istitutotumori.mi.it
                Article
                S2059-7029(21)00130-7 100170
                10.1016/j.esmoop.2021.100170
                8182432
                34090171
                da7597ff-75b2-4ab7-9320-207c0c75b4c5
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Review

                sarcoma,epithelioid hemangioendothelioma,diagnosis,treatment,management,guidelines

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