Silvia Stacchiotti1, Noemi Simeone1, Salvatore Lo Vullo2, Giacomo G Baldi3, Antonella Brunello4, Bruno Vincenzi5, Elena Palassini1, GianPaolo Dagrada6, Paola Collini6, Carlo Morosi7, Francesca G Greco7, Marta Sbaraglia8, Angelo P Dei Tos8,9, Luigi Mariani2, Anna Maria Frezza1, Paolo G Casali1,2,3,4,5,6,7,8,9,10. 1. Department of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy. 2. Unit of Clinical Epidemiology and Trial Organization, IRCCS Foundation National Cancer Institute, Milan, Italy. 3. Department of Medical Oncology, Santo Stefano Hospital, Prato, Italy. 4. Department of Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology, IRCCS, Padua, Italy. 5. Department of Medical Oncology, Biomedical Campus, University of Rome, Rome, Italy. 6. Department of Diagnostic Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy. 7. Department of Radiology, IRCCS Foundation National Cancer Institute, Milan, Italy. 8. Department of Pathology, University of Padua Foundation, Padua, Italy. 9. Department of Medicine, University of Padua, Padua, Italy. 10. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Abstract
BACKGROUND: 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. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing 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-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven 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-month median follow-up (interquartile range [IQR], 23.9-56.8 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, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing 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-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven 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-month median follow-up (interquartile range [IQR], 23.9-56.8 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, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 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. CONCLUSIONS: 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.
Authors: Anna M Frezza; Vinod Ravi; Salvatore Lo Vullo; Bruno Vincenzi; Francesco Tolomeo; Tom Wei-Wu Chen; Pawel Teterycz; Giacomo G Baldi; Antoine Italiano; Nicolas Penel; Antonella Brunello; Florance Duffaud; Nadia Hindi; Shintaro Iwata; Alannah Smrke; Alexander Fedenko; Hans Gelderblom; Winette Van Der Graaf; Aurore Vozy; Elizabeth Connolly; Massimiliano Grassi; Robert S Benjamin; Javier-Martin Broto; Giovanni Grignani; Robin L Jones; Akira Kawai; Andrzej Tysarowski; Luigi Mariani; Paolo G Casali; Silvia Stacchiotti Journal: Cancer Med Date: 2021-03-13 Impact factor: 4.452