title: The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development.
abstract: Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development.
  
  
  
  Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (<0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer.
  
  
  
  After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor.
  
  
  
  In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain. Electronic address: pablosanchezsalcedo@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sanchez-Salcedo
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: de-Torres
authors.affiliation: Internal Medicine Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Martinez-Urbistondo
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gonzalez-Gutierrez
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Berto
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Arantzazu
authors.initials: A
authors.lastname: Campo
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Alcaide
authors.affiliation: Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Javier J
authors.initials: JJ
authors.lastname: Zulueta
mesh_terms: D000368:Aged; D015415:Biomarkers; D055088:Early Detection of Cancer; D004646:Emphysema / Q000000981:diagnostic imaging / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D010976:Platelet Count; D011237:Predictive Value of Tests; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology; D018570:Risk Assessment; D013147:Spirometry; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D015415:Biomarkers
keywords: Emphysema; Lung cancer; Lung cancer screening; NLR; Neutrophil-to-lymphocyte ratio; PLR; Platelet-to-lymphocyte ratio