title: Prognostic value of neutrophil-to-lymphocyte ratio in advanced oesophago-gastric cancer: exploratory analysis of the REAL-2 trial.
abstract: BACKGROUND
  The REAL-2 trial demonstrated that capecitabine and oxaliplatin were effective alternatives to fluorouracil and cisplatin, respectively, when used in triplet chemotherapy regimens for previously untreated oesophago-gastric cancer. The aim of the current analysis was to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in the REAL-2 cohort.
  
  
  METHODS
  A post hoc exploratory analysis was carried out on REAL-2 patients with the available absolute neutrophil count and absolute lymphocyte count. A high NLR was defined using a cut-off value of >3.0. The NLR was then correlated with clinical outcomes including overall survival (OS), progression-free survival (PFS) and objective response rate. Survival curves were generated using the Kaplan-Meier method and comparison between groups was carried out using Cox regression.
  
  
  RESULTS
  Data were available in 908 of the 1002 REAL-2 participants. Of these, 516 (56.8%) were deemed to have a high NLR. In univariate analysis, high NLR was associated with a hazard ratio (HR) for OS of 1.73 (1.50-2.00), P < 0.001, compared with low NLR, equating to median OS values of 9.1 [95% confidence interval (CI) 8.0-9.6] and 12.7 months (95% CI 10.8-14.4), respectively. The NLR remained highly significant for OS (P < 0.001) in a multivariate model including performance status, age, disease extent, presence of liver metastases and presence of peritoneal metastases. For PFS, high NLR was associated with an HR of 1.63 (1.41-1.87), P < 0.001, compared with low NLR in univariate analysis. No significant interaction was found between NLR status and treatment arm, 13% of all patients with low NLR achieving survival beyond 24 months compared with only 6% of patients with high NLR (P < 0.001).
  
  
  CONCLUSIONS
  Our results confirm that high NLR status had a significant negative prognostic effect in the REAL-2 trial population. Based on the multivariate analysis, this effect was independent of other known prognostic factors.
authors.affiliation: Oncology Institute, Shaare Zedek Medical Centre, Jerusalem, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Grenader
authors.affiliation: Section of GI and Lymphoma Units, Department of Medicine, The Royal Marsden Hospital, London.
authors.forename: T
authors.initials: T
authors.lastname: Waddell
authors.affiliation: Clinical Research and Development, The Royal Marsden NHS Foundation Trust, London.
authors.forename: C
authors.initials: C
authors.lastname: Peckitt
authors.affiliation: Section of GI and Lymphoma Units, Department of Medicine, The Royal Marsden Hospital, London.
authors.forename: J
authors.initials: J
authors.lastname: Oates
authors.affiliation: Section of GI and Lymphoma Units, Department of Medicine, The Royal Marsden Hospital, London.
authors.forename: N
authors.initials: N
authors.lastname: Starling
authors.affiliation: Section of GI and Lymphoma Units, Department of Medicine, The Royal Marsden Hospital, London.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Department of Oncology, UCL Cancer Institute, London, UK j.bridgewater@ucl.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Bridgewater
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069287:Capecitabine / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D002945:Cisplatin
keywords: ECF; ECX; EOF; EOX; neutrophil-to-lymphocyte ratio; oesophago-gastric cancer