{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:23:25Z","timestamp":1792423405877,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,2,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From January 2005, 38 adult patients with advanced EHE received continuous\u2010dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan\u2010Meier method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]\u2010positive, n = 37; transcription factor E3 [TFE3]\u2010positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty\u2010seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5\u2010month median follow\u2010up (interquartile range [IQR], 23.9\u201056.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5\u201011.7 months), and the median OS was 10.6 months (IQR, 5.1\u201013.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation\/ovary disfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33247","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T13:37:51Z","timestamp":1603805871000},"page":"569-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case\u2010series analysis within the Italian Rare Cancer Network"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1742-8666","authenticated-orcid":false,"given":"Silvia","family":"Stacchiotti","sequence":"first","affiliation":[{"name":"Department of Medical Oncology IRCCS Foundation National Cancer Institute Milan 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Cancer Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Collini","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Laboratory Medicine IRCCS Foundation National Cancer Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Morosi","sequence":"additional","affiliation":[{"name":"Department of Radiology IRCCS Foundation National Cancer Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca G.","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Radiology IRCCS Foundation National Cancer Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sbaraglia","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Padua Foundation Padua 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