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A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas.

ABSTRACT: Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0-7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5-7). The hallmarks of cancer feature 'immune' was most significantly associated with worse OS (HR 1.88, (95%CI 1.20-2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer.

SUBMITTER: Creemers A

PROVIDER: S-EPMC6125467 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas.

Creemers Aafke A Ebbing Eva A EA Pelgrim Thomas C TC Lagarde Sjoerd M SM van Etten-Jamaludin Faridi S FS van Berge Henegouwen Mark I MI Hulshof Maarten C C M MCCM Krishnadath Kausilia K KK Meijer Sybren L SL Bijlsma Maarten F MF van Oijen Martijn G H MGH van Laarhoven Hanneke W M HWM

Scientific reports 20180905 1

Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0-7 points based on modified REMARK criteria. To evaluate all identified prognostic biomark ...[more]

PMID: 30185893

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Project description:BackgroundCarcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.MethodsA systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.ResultsThirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.ConclusionFor adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.

Project description:Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available evidence on prognostic factors associated with perihilar cholangiocarcinoma after resection. The PubMed, Embase, and Cochrane library were systematically searched for relevant studies published before December 2019. Prognostic factors were identified from multivariate regression analyses in studies. Only high-quality studies were included (Newcastle-Ottawa Scale > 6 stars). A total of 45 studies involving 7338 patients were analyzed. The meta-analysis demonstrated that serum bilirubin levels (hazard ratio: 1.76, 95% confidence interval: 1.27-2.44), serum CA19-9 levels (hazard ratio: 1.32, 95% confidence interval: 1.05-1.65), tumor size (hazard ratio: 1.27, 95% confidence interval: 1.04-1.55), major vascular involvement (hazard ratio: 1.61, 95% confidence interval: 1.09-2.38), distance metastasis (hazard ratio: 17.60, 95% confidence interval: 2.01-154.09), perioperative blood transfusion (hazard ratio: 1.36, 95% confidence interval: 1.15-1.62), T-stage (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61), lymph node metastasis (hazard ratio: 2.06, 1.83-2.31), resection margin status (hazard ratio: 2.34, 95% confidence interval: 1.89-2.89), not-well histology differentiation (hazard ratio: 2.03, 95% confidence interval: 1.69-2.44), perineural invasion (hazard ratio: 2.37, 95% confidence interval: 1.59-3.55), and lymphovascular invasion (hazard ratio: 1.41, 95% confidence interval: 1.15-1.73) were prognostic factors for poorer overall survival. Adjuvant chemotherapy (hazard ratio: 0.37, 95% confidence interval: 0.25-0.55) had a positive effect on prolonged overall survival. In addition, positive resection margin status (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61) and lymph node metastasis (hazard ratio: 2.06, 95% confidence interval: 1.83-2.31) were associated with poorer disease-free survival. The prognostic factors identified in the present meta-analysis can be used to characterize patients in clinical practice and enrich prognostic tools, which could be included in future trial designs and generate hypotheses to be tested in future research to promote personalized treatment.

Dataset Information

A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas.

Publications

A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas.

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