Silvia Stacchiotti1, Salvatore Provenzano2, Gianpaolo Dagrada3, Tiziana Negri3, Silvia Brich3, Umberto Basso4, Antonella Brunello4, Federica Grosso5, Luca Galli6, Elena Palassini2, Michela Libertini2, Vittoria Colia2, Alessandro Gronchi7, Angelo P Dei Tos8, Flavio Crippa9, Carlo Morosi10, Silvana Pilotti3, Paolo G Casali2. 1. Medical Oncology Unit 2 - Adult Mesenchymal Tumours and Rare Cancers, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it. 2. Medical Oncology Unit 2 - Adult Mesenchymal Tumours and Rare Cancers, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 3. Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 4. Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy. 5. Oncology, SS Antonio e Biagio General Hospital, Alessandria, Italy. 6. Oncology, Santa Chiara Hospital, Pisa, Italy. 7. Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 8. Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy. 9. Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 10. Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
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.
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.
Authors: Anna Karastaneva; Paolo Gasparella; Sebastian Tschauner; Roman Crazzolara; Gabriele Kropshofer; Manfred Modl; Andreas Pfleger; Ante Burmas; Mirjam Pocivalnik; Raphael Ulreich; Werner Zenz; Wolfgang Schwinger; Besiana P Beqo; Christian Urban; Emir Q Haxhija; Herwig Lackner; Martin Benesch Journal: Front Pediatr Date: 2022-05-23 Impact factor: 3.569
Authors: Jordan H Driskill; Yonggang Zheng; Bo-Kuan Wu; Li Wang; Jing Cai; Dinesh Rakheja; Michael Dellinger; Duojia Pan Journal: Genes Dev Date: 2021-03-25 Impact factor: 11.361
Authors: Anna Maria Frezza; Alex T J Lee; Eran Nizri; Marta Sbaraglia; Robin L Jones; Alessandro Gronchi; Angelo Paolo Dei Tos; Paolo G Casali Journal: ESMO Open Date: 2018-06-28