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      Neutrophil counts and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

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          Abstract

          OBJECTIVE: To evaluate the strength and validity of evidence on the association between the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. DESIGN: Umbrella review of systematic reviews and meta-analyses of observational studies. DATA SOURCES: Medline, EMBASE, Cochrane Database of Systematic Reviews and manual screening of retrieved references. ELIGIBILITY CRITERIA: Systematic reviews or meta-analyses of observational studies evaluating the association between NLR or TAN and specific cancer outcomes related to disease progression or survival. DATA SYNTHESIS: The available evidence was graded as strong, highly suggestive, suggestive, or weak through the application of pre-set grading criteria. For each included meta-analysis, the grading criteria considered the significance of the random effects estimate, the significance of the largest included study, the number of studies and individuals included, the heterogeneity between included studies, the 95% prediction intervals, presence of small study effects, excess significance and credibility ceilings. RESULTS: 239 meta-analyses investigating the association between NLR or TAN and cancer outcomes were identified from 57 published studies meeting the eligibility criteria, with 81 meta-analyses from 36 studies meeting the criteria for inclusion. No meta-analyses found a hazard ratio (HR) in the opposite direction of effect (HR<1). When assessed for significance and bias related to heterogeneity and small study effects, only three (4%) associations between NLR and outcomes in gastrointestinal and nasopharyngeal cancers were supported by strong evidence. CONCLUSION: Despite many publications exploring the association between NLR and cancer prognosis, the evidence is limited by significant heterogeneity and small study effects. There is a lack of evidence on the association between TAN and cancer prognosis, with all nine associations identified arising from the same study. Further research is required to provide strong evidence for associations between both TAN and NLR and poor cancer prognosis.

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          Author and article information

          Journal
          bioRxiv
          May 25 2018
          Article
          10.1101/330076
          a14a321f-f963-4ca9-86fe-28c9a6721c46
          © 2018
          History

          Evolutionary Biology,Medicine
          Evolutionary Biology, Medicine

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