title: The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials.
abstract: BACKGROUND
  Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.
  
  
  METHODS
  This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.
  
  
  RESULTS
  The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.
  
  
  CONCLUSIONS
  NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Geuna
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: V
authors.initials: V
authors.lastname: Michalarea
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Guardascione
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Downs Road, Sutton, Surrey, London SM2 5NG, UK.
authors.forename: U
authors.initials: U
authors.lastname: Naumann
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: D
authors.initials: D
authors.lastname: Lorente
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000368:Aged; D017321:Clinical Trials, Phase I as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis