A retrospective review of neutrophil-lymphocyte ratio as a predictive prognostic marker in upper gastrointestinal cancers in three UK hospitals over a nine year period
Authors: N. Wreglesworth, C. Roberts, P. Innominato
Journal: Annals of Oncology (2018)

Introduction: Several studies suggest the predictive role of a high neutrophil-to-lymphocyte ratio (NLR) leading to poor pan-cancer prognosis. We explored the predictive value of NLR in a cohort of upper GI cancer patients but also the potential additive predictive effects to NLR of platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and total protein (TPROT). We retrospectively reviewed data from a cohort of consecutive upper GI cancer patients collected over a 9 year period (2007 to 2016). Methods: We reviewed our digital prescribing system across three UK based hospitals. All the patients included were referred to oncology services after their initial diagnosis. The data BMI, eGFR, PS, chemotherapy details, presence of metastases, sex and blood parameters were retrieved before chemotherapy started. Overall survival (OS) was the primary outcome. Multivariate Cox proportional hazard models were built using NLR as either quantitative or median-split variable. Results: Our cohort included 302 cancer patients with: 113(37.3%) of the oesophagus, 84(27.6%) of the stomach, and 105(34.5%) of the pancreas. The median age of the patients was 66 years old (range 30-85). There was a 1:2 female:male ratio. Of these patients; 92(30%) were categorised as metastatic (M1) and 262(86.2%) had died at the time of analysis (March 2017). Over a nine-year period across three cancer locations chemotherapy regimens changed so we included number of cycles of chemotherapy the patients had received, the mean being 4.7 (0-35). Median NLR was 2.57 (a similar figure to previous studies), and respective 25th and 75th percentiles were 1.34 and 5.29. A higher than 2.57 NLR was significantly and robustly associated to a poor prognosis independently of age, location of primary, eGFR, number of chemotherapy cycles, presence of metastases, sex, BMI and PS (where available) (HR: 1.445; p = 0.018). Thus, median OS was 15.14 months [95% confidence limits (CL): 11.45-18.84] in the group of patients with low NLR in comparison to 7.524 [6.02-9.02] in patients with high NLR. The difference in outcomes according to NLR was comparable in each cancer separately: oesophagus, median OS dropping from 12.6 to 9 months; stomach, 18.0 to 8.7; pancreas, 13.0 to 5.3 (p < 0.001). We could not identify any individual or additive effects of PLR, MLR or TPROT either as continuous or quartile-categorized data. Conclusion: NLR appears a reliable prognostic predictor in this cohort of upper GI cancers. There was no apparent effect of PLR, MLR nor TPROT in our study. A high NLR suggests significantly poorer prognosis. In this study, results are similar amongst all three upper GI cancers investigated over a long-time period during which chemotherapy regimens were variable. The results appear independent of other commonly associated poor prognostic indicators such as presences of metastases, BMI, eGFR and age. Baseline NLR is confirmed here as a simple measure to predict prognosis in upper GI oncology patients about to embark on chemotherapy. Additional research is warranted to assess such an easy marker with regards to prediction of optimal therapeutic option and as a time-dependent variable, to substantiate its relevance in potentially influencing clinical practice.