Prognostic value of monocyte and neutrophils to lymphocytes ratio in patients with metastatic soft tissue sarcoma.
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ABSTRACT:
SUBMITTER: Jiang L
PROVIDER: S-EPMC4496237 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
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Prognostic value of monocyte and neutrophils to lymphocytes ratio in patients with metastatic soft tissue sarcoma.
Jiang Long L Jiang Shanshan S Situ Dongrong D Lin Yongbin Y Yang Han H Li Yuanfang Y Long Hao H Zhou Zhiwei Z
Oncotarget 20150401 11
Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago. Prognosis of cancer patients are based not only on tumor-related factors but also on host-related factors, particularly systemic inflammatory response. We evaluated the association among possible risk factors and survival for metastatic STS by reviewed a single-institution nearly 50-year experience. We found that both monocyte ratio and NLR ratio w ...[more]
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Project description:BACKGROUND:Coagulation and nutrition play important roles in cancer progression. The aim of the present study is to evaluate the prognostic value of the preoperative fibrinogen/albumin ratio (FAR) in surgical patients with soft tissue sarcoma (STS) and to compare this value with other inflammatory biomarkers. In addition, we investigated the relationship between FAR and the clinicopathological characteristics of STS patients. METHODS:We included 310 STS patients in this retrospective study. Kaplan-Meier curves, univariate and multivariate Cox proportional models were used in the prognostic analyses. RESULTS:According to the receiver operating characteristic (ROC) analysis, the optimal FAR cut-off value was 0.0726. The FAR exhibited a greater area under the curve (AUC) value (0.680) than did the NLR and PLR. An elevated FAR (?0.0726) was significantly associated with an old age, large tumor size, deep tumor location, high tumor grade, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with an increased FAR had a shorter median survival time and a lower 5-year overall survival (OS) rate than did those with a low FAR (61.0 vs115.8 months, P < 0.001; 56.7% vs 82.4%, P < 0.001, respectively). Multivariate analysis indicated FAR (Hazard ratio (HR) 1.907, 95% confidence interval (CI) 1.161-3.132, P < 0.001) to be an independent prognostic factor for OS, as were tumor depth, grade and PLR. CONCLUSIONS:Preoperative FAR is associated with tumor progression and can be considered an independent factor for OS of resected STS patients.
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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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Project description:Soft tissue sarcomas are a form of rare and heterogeneous neoplasms with high recurrence rate and mortality. Over the past decades, less progress has been achieved. Surgical management with or without adjuvant/neoadjuvant radiotherapy is still the first-line treatment for localized soft tissue sarcomas, and chemotherapy is the additional option for those with high-risk. However, not all patients with advanced or metastatic soft tissue sarcomas benefit from conventional chemotherapy, targeted therapy takes the most relevant role in the management of those resistant to or failed to conventional chemotherapy. Heterogeneous soft tissue sarcomas vary from biological behavior, genetic mutations, and clinical presentation with a low incidence, indicating the future direction of histotype-based even molecule-based personalized therapy. Furthermore, increasing preclinical studies were carried out to investigate the pathogenesis and potential therapeutic targets of soft tissue sarcomas and increasing new drugs have been developed in recent years, which had started opening new doors for clinical treatment for patients with advanced/metastatic soft tissue sarcomas. Here we sought to summarize the concise characteristics and advance in the targeted therapy for the most common subtypes of soft tissue sarcomas.
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Project description:We hypothesize that there is a gene signature which will improve our ability to predict development of metastatic disease in STS patients. The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus non-metastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR confirmed increased relative expression of all five genes of interest in the metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible methods for comparing gene signatures in canine STSs. Further evaluation of differences in gene expression between metastatic and non-metastatic STSs is likely to identify genes important in the development of metastatic disease and improve our ability to prognosticate for individual patients.
2011-02-01 | GSE24601 | GEO
Project description:We hypothesize that there is a gene signature which will improve our ability to predict development of metastatic disease in STS patients. The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus non-metastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR confirmed increased relative expression of all five genes of interest in the metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible methods for comparing gene signatures in canine STSs. Further evaluation of differences in gene expression between metastatic and non-metastatic STSs is likely to identify genes important in the development of metastatic disease and improve our ability to prognosticate for individual patients. Comparison of metastatic and non-metastatic (defined as no metastasis for at least one year) untreated tumor biopsies.
2011-02-01 | E-GEOD-24601 | biostudies-arrayexpress
Project description:BackgroundMetastatic 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.MethodsWe 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.ResultsOut 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.ConclusionsVery 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.
| S-EPMC6488206 | biostudies-literature