title: Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.
abstract: BACKGROUND
  The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer.
  
  
  METHODS
  A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR = ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of ⩾ 2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan-Meier method. Comparison between groups was performed using Cox regression.
  
  
  RESULTS
  A total of 1630 patients were assigned to the continuous (N = 815) or intermittent (N = 815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR = 1.70; 95% CI = 1.52-1.90; P < 0.001). The estimate of the hazard ratio did not alter substantially (HR = 1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count.
  
  
  CONCLUSIONS
  Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy.
authors.affiliation: Oncology Institute, Shaare Zedek Medical Centre, Serusatem, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Grenader
authors.affiliation: Cancer Research UK & UCL Cancer Trials Centre, London WIT 4TJ4TJ, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Nash
authors.affiliation: Institute of Cancer & Genetics, Cardiff University School of Medicine Velindre Hospital, Cardiff CF14 2TL, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Adams
authors.affiliation: MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
authors.affiliation: MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Fisher
authors.affiliation: CRUK/MRC Oxford Institute for Radiation, Oxford OX3 7DQ, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Maughan
authors.affiliation: UCL Cancer Institute, London WC1E 6DD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Bridgewater
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage; D015996:Survival Rate; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; C029269:5-fluoropyrimidine; D000068818:Cetuximab