BackgroundRecently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, >= 10 adult patients) to update long-standing reference values for... Show moreBackgroundRecently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, >= 10 adult patients) to update long-standing reference values for leiomyosarcomas. This work is extended for liposarcomas (LPS) and synovial sarcomas (SS).Materials and methodsStudy endpoints were progression-free survival rates (PFSRs) at 3 and 6 months. Trial-specific estimates were pooled per treatment line (first-line or pre-treated) with random effects meta-analyses. The choice of the therapeutic benefit to target in future trials was guided by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).ResultsInformation was acquired for 1030 LPS patients (25 trials; 7 first-line, 17 pre-treated, 1 both) and 348 SS patients (13 trials; 3 first-line, 10 pre-treated). For LPS, the overall pooled first-line PFSRs were 69% (95%-CI 60-77%) and 56% (95%-CI 45-67%) at 3 and 6 months, respectively. These rates were 49% (95%-CI 40-57%)/28% (95%-CI 22-34%) for >1 lines. For SS, first-line PFSRs were 74% (95%-CI 58-86%)/56% (95%-CI 31-78%) at 3 and 6 months, and pre-treated rates were 45% (95%-CI 34-57%)/25% (95%-CI 16-36%). Following ESMO-MCBS guidelines, the minimum values to target are 79% and 69% for first-line LPS (82% and 69% for SS) at 3 and 6 months. For pre-treated LPS, recommended PFSRs at 3 and 6 months suggesting drug activity are 63% and 44% (60% and 41% for SS).ConclusionsNew benchmarks are proposed for advanced/metastatic LPS or SS to design future histology-specific phase II trials. More data are needed to provide definitive thresholds for the different LPS subtypes. 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Kantidakis, G.; Litiere, S.; Neven, A.; Vinches, M.; Judson, I.; Schoffski, P.; ... ; Gelderblom, H. 2021
Background: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft... Show moreBackground: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS). Materials and methods: Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003-2018, >10 adult LMS patients). End-points were 3-and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials. Results: From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64-82%) and 58% (95% CI 50-66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41-54%), and PFSR-6m was 28% (95% CI 22-34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m >70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m >62% or PFSR-6m >44% would suggest drug activity. Specific results are also provided for uterine LMS. Conclusions: This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus... Show moreBackground The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first-line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) sites.Methods The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status <= 2, and an age >= 18 years. The endpoints were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval-censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent.Results Three hundred three patients from 18 EORTC-STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score-matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2-9.7 months), 8.2 months (95% CI, 5.2-10.1 months), and 4.8 months (95% CI, 2.3-6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7-33.4 months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0-36.3 months; HR, 0.66; 95% CI, 0.43-0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS.Conclusions This is the largest retrospective study of first-line treatment for advanced leiomyosarcoma. In the propensity score-matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials. Show less
The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing... Show moreThe continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Show less
