Prognostic value of neutrophil-to-lymphocyte ratio in advanced oesophago-gastric cancer: exploratory analysis of the REAL-2 trial

Ann Oncol. 2016 Apr;27(4):687-92. doi: 10.1093/annonc/mdw012. Epub 2016 Jan 19.


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.

Material and 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).

Conclusion: 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.

Keywords: ECF; ECX; EOF; EOX; neutrophil-to-lymphocyte ratio; oesophago-gastric cancer.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Capecitabine / administration & dosage*
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Organoplatinum Compounds / administration & dosage*
  • Oxaliplatin
  • Prognosis
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology


  • Organoplatinum Compounds
  • Oxaliplatin
  • Capecitabine
  • Cisplatin