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Prognostic value of neutrophil to lymphocyte ratio in advanced oesophago-gastric cancer: exploratory analysis of the REAL-2 trial
Grenader T, Waddell T, Peckitt C, Oates J, Starling N, Cunningham D, Bridgewater J.
Ann Oncol. 2016 Jan 19 [Epub ahead of print]
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 neutrophil to lymphocyte ratio (NLR) in the REAL-2 cohort.
MATERIAL AND METHODS:
A post-hoc exploratory analysis was performed on REAL-2 patients with available absolute neutrophil count and absolute lymphocyte count. A high NLR, defined using a cut-off value of >3.0. NLR, was then correlated with clinical outcomes including overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Survival curves were generated using the Kaplan-Meier method and comparison between groups was performed using cox regression.
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 for OS of 1.73 (1.50 - 2.00), p<0.001, compared to low NLR, equating to median OS values of 9.1 (95% CI 8.0 to 9.6) and 12.7 months (95% CI 10.8 to 14.4) respectively. NLR remained highly significant for OS (p<0.001) in a multi-variate model including PS, age, disease extent, presence of liver metastases, and presence of peritoneal metastases.For PFS, high NLR was associated with a hazard ratio of 1.63 (1.41 - 1.87), p<0.001, compared to 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 to only 6% of patients with high NLR (p<0.001).
Our results confirm that high NLR status had a significant negative prognostic effect in the REAL-2 trial population. Based on the multi-variate analysis, this effect was independent of other known prognostic factors.