Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature

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Abstract

Background

This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra‐rare sarcoma, marked by WWTR1‐ CAMTA1 or YAP1‐ TFE3 fusions.

Methods

Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan‐Meier method.

Results

Overall, 73 patients were included; 21 had more than one treatment. Thirty‐three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m‐) PFS and m‐OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m‐PFS and m‐OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m‐PFS and m‐OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF‐α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m‐PFS and m‐OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported.

Conclusion

Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Abstract

Anthracycline‐based regimens, the standard first line treatment in advanced soft tissue sarcomas, paclitaxel and pazopanib have a very limited activity in advanced, progressive epithelioid haemangioendothelioma. In the absence of available, potentially active medical therapies, epithelioid haemangioendothelioma remains today an unmet clinical need.

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Most cited references 37

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Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

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Author and article information

Contributors

Anna M. Frezza:

ORCID: https://orcid.org/0000-0003-2335-7224

annamaria.frezza@istitutotumori.mi.it

Journal

Journal ID (nlm-ta): Cancer Med

Journal ID (iso-abbrev): Cancer Med

Journal ID (doi): 10.1002/(ISSN)2045-7634

Journal ID (publisher-id): CAM4

Title: Cancer Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2045-7634

Publication date (Electronic): 13 March 2021

Publication date Collection: April 2021

Volume: 10

Issue: 8 ( doiID: 10.1002/cam4.v10.8 )

Pages: 2645-2659

Affiliations

[ ¹ ] Department of Medical Oncology IRCCS Fondazione Istituto Nazionale Tumori Milano Italy

[ ² ] Department of Sarcoma Medical Oncology The University of Texas MD Anderson Cancer Center Houston Italy

[ ³ ] Unit of Clinical Epidemiology and Trial Organization IRCCS Fondazione Istituto Nazionale Tumori Milano Italy

[ ⁴ ] Department of Medical Oncology Università Campus Bio‐Medico di Roma Roma Italy

[ ⁵ ] Division of Medical Oncology Candiolo Cancer Institute FPO ‐ IRCCS Candiolo Torino Italy

[ ⁶ ] Department of Oncology National Taiwan University Hospital and Graduate Institute of Oncology National Taiwan University College of Medicine Taipei Taiwan

[ ⁷ ] Department of Soft Tissue/Bone Sarcoma and Melanoma Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland

[ ⁸ ] Department of Medical Oncology Nuovo Ospedale "S.Stefano" Prato Italy

[ ⁹ ] Early Phase Trials and Sarcoma Units Institut Bergonié Bordeaux France

[ ¹⁰ ] Medical Oncology Department Centre Oscar Lambret Lille France

[ ¹¹ ] Medical School Lille University Lille France

[ ¹² ] Department of Oncology Medical Oncology 1 Unit Istituto Oncologico Veneto IRCCS Padova Italy

[ ¹³ ] Department of Medical Oncology Medical Oncology La Timone University Hospital Aix‐Marseille Université (AMU Marseille France

[ ¹⁴ ] Medical Oncology Department University Hospital Virgen del Rocio, and Institute of Biomedicine Sevilla Spain

[ ¹⁵ ] Department of Musculoskeletal Oncology National Cancer Center Hospital Tokyo Japan

[ ¹⁶ ] Sarcoma Unit Royal Marsden NHS Foundation Trust/ Institute of Cancer Research, Chelsea London United Kingdom

[ ¹⁷ ] Division of Medical Oncology P.A. Herzen Cancer Research Institute Moscow Russian Federation

[ ¹⁸ ] Department of Medical Oncology Leiden University Medical Center Leiden the Netherlands

[ ¹⁹ ] Department of Medical Oncology Radboud University Medical Centre Nijmegen Nijmegen The Netherlands

[ ²⁰ ] Department of Medical Oncology Pitié Salpétrière Hospital Paris France

[ ²¹ ] Department Of Medical Oncology Chris O'Brien Lifehouse Sydney Australia

[ ²² ] Medical Oncology Unit 1 Ospedale Policlinico San Martino IRCCS University of Genoa Genoa Italy

[ ²³ ] Pathology department Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland

[ ²⁴ ] Department of Oncology and Hemato‐oncology University of Milan Milan Italy

Author notes

[*] [* ] Correspondence

Anna M. Frezza, MD, Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy.

Email: annamaria.frezza@ 123456istitutotumori.mi.it

Author information

Anna M. Frezza https://orcid.org/0000-0003-2335-7224

Salvatore Lo Vullo https://orcid.org/0000-0002-4444-9526

Tom Wei‐Wu Chen https://orcid.org/0000-0003-4112-4029

Pawel Teterycz https://orcid.org/0000-0001-7304-714X

Antoine Italiano https://orcid.org/0000-0002-8540-5351

Antonella Brunello https://orcid.org/0000-0003-2583-5226

Giovanni Grignani https://orcid.org/0000-0001-5515-569X

Robin L. Jones https://orcid.org/0000-0003-4173-3844

Akira Kawai https://orcid.org/0000-0003-2116-586X

Silvia Stacchiotti https://orcid.org/0000-0002-1742-8666

Article

Publisher ID: CAM43807

DOI: 10.1002/cam4.3807

PMC ID: 8026938

PubMed ID: 33713582

SO-VID: 5c40b37c-c404-4e03-be07-c561514090dc

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 25 January 2021

Date received : 17 January 2021

Date accepted : 09 February 2021

Page count

Figures: 3, Tables: 3, Pages: 15, Words: 8572

Custom metadata

source-schema-version-number 2.0

cover-date April 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.1 mode:remove_FC converted:08.04.2021

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: anthracycline,chemotherapy,epithelioid haemangioendothelioma,interferon,paclitaxel,pazopanib

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: anthracycline, chemotherapy, epithelioid haemangioendothelioma, interferon, paclitaxel, pazopanib

Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature

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Abstract

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Most cited references 37

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial.

Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study.

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