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Very long-term survivors among patients with metastatic soft tissue sarcoma.

ABSTRACT: BACKGROUND:Metastatic soft tissue sarcomas (STS) are a group of rare and heterogeneous mesenchymal?tumors with a poor prognosis. The aim of this study was to evaluate the incidence of long-term survivors and describe their presentation and management in a large cohort of patients with metastatic STS. METHODS:We collected information of patients with metastatic STS managed in Centre Leon?Berard?between 1985 and 2015 aiming to compare the group of patients alive 5 years after the diagnosis of metastases vs the others. Prognostic factors of patients and tumors characteristics were investigated by logistic regression analysis. For "long-term survivors," we explored therapeutic strategies at metastatic stage. RESULTS:Out of 436 patients enrolled, 39 (9%) were still alive 5 years after diagnostic of metastases with a median survival of 146 months (12 years). This "long-term survivors" group included more female and younger patients, with better performance status, more synovial sarcoma or endometrial stromal sarcoma, more patients with simple genomic sarcomas, lower tumor grade, smaller?tumor, and longer disease-free interval. In multivariate analysis, age below 55 at metastatic stage (P = 0.0002) and?grade 1?tumor (P < 0.0001) were significantly associated with the "long-term survivors." Their therapeutic management was usually aggressive (intensified or polychemotherapy, repeated local treatment of metastases), leading to 62% of complete response in first-line setting. CONCLUSIONS:Very long-term survivors are observed in metastatic STS. Selection of patients in good condition with less aggressive tumor and administration of intensive treatment may lead to obtain these motivating results in a poor prognosis disease.

SUBMITTER: Carbonnaux M

PROVIDER: S-EPMC6488206 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Project description:Objective: Trabectedin is an anti-cancer drug commonly used for the treatment of patients with metastatic soft tissue sarcoma (mSTS). Despite its recognized efficacy, significant variability in pharmacological response has been observed among mSTS patients. To address this issue, this pharmacometabolomics study aimed to identify pre-dose plasma metabolomics signatures that can explain individual variations in trabectedin pharmacokinetics and overall clinical response to treatment. Methods: In this study, 40 mSTS patients treated with trabectedin administered by 24 h-intravenous infusion at a dose of 1.5 mg/m2 were enrolled. The patients' baseline plasma metabolomics profiles, which included derivatives of amino acids and bile acids, were analyzed using multiple reaction monitoring LC-MS/MS together with their pharmacokinetics profile of trabectedin. Multivariate Partial least squares regression and univariate statistical analyses were utilized to identify correlations between baseline metabolite concentrations and trabectedin pharmacokinetics, while Partial Least Squares-Discriminant Analysis was employed to evaluate associations with clinical response. Results: The multiple regression model, derived from the correlation between the AUC of trabectedin and pre-dose metabolomics, exhibited the best performance by incorporating cystathionine, hemoglobin, taurocholic acid, citrulline, and the phenylalanine/tyrosine ratio. This model demonstrated a bias of 4.6% and a precision of 17.4% in predicting drug AUC, effectively accounting for up to 70% of the inter-individual pharmacokinetic variability. Through the use of Partial least squares-Discriminant Analysis, cystathionine and hemoglobin were identified as specific metabolic signatures that effectively distinguish patients with stable disease from those with progressive disease. Conclusions: The findings from this study provide compelling evidence to support the utilization of pre-dose metabolomics in uncovering the underlying causes of pharmacokinetic variability of trabectedin, as well as facilitating the identification of patients who are most likely to benefit from this treatment. Graphical Abstract

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Very long-term survivors among patients with metastatic soft tissue sarcoma.

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