Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established.... Show morePurpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort.Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival.Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location.Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted. Show less
Background We aimed at investigating outcome of systemic treatments in advanced breast PT. Methods All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the... Show moreBackground We aimed at investigating outcome of systemic treatments in advanced breast PT. Methods All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. Results 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. Conclusion In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active. Show less
Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established.... Show morePurpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort.Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival.Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location.Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted. Show less
Frezza, A.M.; Ravi, V.; Vullo, S. lo; Vincenzi, B.; Tolomeo, F.; Chen, T.W.W.; ... ; Stacchiotti, S. 2021
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... Show moreBackground 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-alpha 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. Show less
Objective: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.Background: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure... Show moreObjective: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.Background: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.Methods: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.Results: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.Conclusion: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Frezza, A.M.; Jones, R.L.; Vullo, S. lo; Asano, N.; Lucibello, F.; Ben-Ami, E.; ... ; Stacchiotti, S. 2018
