Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. Methods A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary

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... me, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a metaanalysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. Results One hundred studies comprising 40 559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). Conclusions A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation. JNCI J Natl Cancer Inst (2014) 106(6): dju124 doi:10.1093/jnci/dju124 of the peripheral blood NLR, and 2) availability of a hazard ratio (HR) and 95% confidence interval (CI) or a P value for overall survival (OS). For a secondary analysis, studies providing a hazard ratio for cancer-specific survival (CSS), progression-free survival (PFS), disease-free survival (DFS), or recurrence-free survival (RFS) were included as well. Duplicate publications were excluded. Two reviewers (A. Templeton, M. McNamara) evaluated independently all of the titles identified by the search strategy. The results were then pooled, and all potentially relevant publications were retrieved in full. The same two reviewers then assessed the full articles for eligibility. Inter-reviewer agreement was assessed using Cohen's kappa. Disagreement was resolved by consensus. Corresponding authors were contacted to clarify missing or ambiguous data. To avoid inclusion of duplicated or overlapping data, we compared author names and institutions where patients were recruited and contacted authors to address potential concerns. In cases where no answer was obtained and substantial doubts remained, the study reporting fewer patients was not included in the analysis. Data Extraction OS was the primary outcome of interest. CSS, PFS, and DFS were secondary outcomes. Data were collected using predesigned abstraction forms. The following details were extracted: name of first author, type of publication (abstract, full text), year of publication, journal, number of patients included in analysis, disease site, disease stage (nonmetastatic, metastatic, mixed [nonmetastatic and metastatic]), collection of data (prospective, retrospective), cutoff defining high NLR used for peripheral blood NLR, consideration of receiver operating characteristic curves (C-index) for selection of cutoff where available, and hazard ratios and associated 95% confidence intervals for OS, PFS, DFS, or RFS as applicable. Hazard ratios were extracted preferentially from multivariable analyses where available. Otherwise, hazard ratios from univariate analyses were extracted.