title: Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis.
abstract: Presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with gynecologic cancers, and examine the effect of clinico-pathologic factors on its prognostic value.
  
  
  
  A systematic search of electronic databases was conducted to identify publications exploring the association of pre-treatment blood NLR with overall survival (OS) and event-free survival (EFS) among patients with ovarian, endometrial and cervical cancers. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p-value (P) were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to primary tumor type. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on the HR for OS and EFS. All statistical tests were two-sided.
  
  
  
  Twenty-six studies comprising 10,530 patients were included. Studies used different cut-offs to classify high NLR (range 0.89 to 5.03). The median cut-off for high NLR was 2.95 among twenty-six studies reporting a HR for OS, and 2.79 in seventeen studies reporting EFS outcomes. NLR greater than the cut-off was associated with worse OS (HR 1.65, 95% CI=1.44 to 1.89; P<0.001) and EFS (HR 1.57, 95% CI=1.35 to 1.82; P<0.001). This association was present in all tumor types. Most studies were comprised of patients with both early-stage and advanced disease. In cervical cancer, significant associations between NLR and OS were observed in studies of early- and mixed-stage patients and regression analysis showed a greater magnitude of effect in patients with locally advanced disease and in those who received both chemotherapy and radiation.
  
  
  
  High NLR is associated with an adverse OS and EFS in patients with gynecologic malignancies.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada. Electronic address: josee-lyne.ethier@uhn.ca.
authors.forename: Josee-Lyne
authors.initials: JL
authors.lastname: Ethier
authors.affiliation: Division of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Desautels
authors.affiliation: Department of Medical Oncology, St. Claraspital Basel and Faculty of Medicine, University of Basel, Basel, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lheureux
mesh_terms: D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
keywords: Cervical cancer; Endometrial cancer; Neutrophil-to-lymphocyte ratio; Ovarian cancer; Overall survival; Prognosis