title: Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy.
abstract: Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies.
  
  
  
  Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma.
  
  
  
  Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC cohort) and 4350 patients from 12 prospective randomized trials (validation cohort).
  
  
  
  Targeted therapies for metastatic renal cell carcinoma.
  
  
  
  NLR was examined at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values at baseline.
  
  
  
  Higher NLR at baseline was associated with shorter OS and PFS (Hazard Ratios [HR] per 1 unit increase in log-transformed NLR = 1.69 [95% confidence interval {CI} = 1.46-1.95] and 1.30 [95% CI = 1.15-1.48], respectively). Compared with no change (decrease < 25% to increase < 25%, reference), increase NLR at Week 6 by 25-50% and > 75% was associated with poor OS (HR=1.55 [95% CI=1.10-2.18] and 2.31 [95% CI=1.64-3.25], respectively), poor PFS (HR=1.46 [95% CI=1.04-2.03], 1.76 [95% CI=1.23-2.52], respectively), and reduced objective response rate (odds ratios = 0.77 [95% CI=0.37-1.63] and 0.24 [95% CI=0.08-0.72], respectively). By contrast, a decrease of 25-50% was associated with improved outcomes. Findings were confirmed in the validation cohort. The study is limited by its retrospective design.
  
  
  
  Compared with no change, early decline of NLR is associated with favorable outcomes, whereas an increase is associated with worse outcomes.
  
  
  
  We found that the proportion of immune cells in the blood is of prognostic value, namely that a decrease of the proportion of neutrophils-to-lymphocytes is associated with more favorable outcomes while an increase had the opposite effect.
authors.affiliation: Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada; Kantonsspital St. Gallen, Department of Medical Oncolgoy and Hematology, St. Gallen, Switzerland.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Pfizer Oncology, Pfizer Inc., New York, NY, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Pfizer Oncology, Pfizer Inc., New York, NY, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Simantov
authors.affiliation: Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA.
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.affiliation: Auckland City Hospital, Auckland City Hospital, Grafton, Auckland, New Zealand.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lawrence
authors.affiliation: Auckland City Hospital, Auckland City Hospital, Grafton, Auckland, New Zealand.
authors.forename: Reuben
authors.initials: R
authors.lastname: Broom
authors.affiliation: Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rini
authors.affiliation: Aarhus University Hospital, Nørrebrogade, Aarhus, Denmark.
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Sunnybrook Odette Cancer Center, Toronto, ON, Canada.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.affiliation: British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Smoragiewicz
authors.affiliation: National Cancer Center Singapore, Singapore.
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada; Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada.
authors.forename: Nimira
authors.initials: N
authors.lastname: Alimohamed
authors.affiliation: Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada.
authors.forename: J Connor
authors.initials: JC
authors.lastname: Wells
authors.affiliation: Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address: daniel.heng@albertahealthservices.ca.
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000368:Aged; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000379:methods*; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D015415:Biomarkers
keywords: Change; Conversion; Neutrophil-to-lymphocyte ratio; Prognosis; Renal cell carcinoma; Targeted therapy