Optimal cut-off for neutrophil-to-lymphocyte ratio: Fact or Fantasy? A prospective cohort study in metastatic cancer patients - PubMed (original) (raw)

Optimal cut-off for neutrophil-to-lymphocyte ratio: Fact or Fantasy? A prospective cohort study in metastatic cancer patients

Yann-Alexandre Vano et al. PLoS One. 2018.

Abstract

This study assessed the prognostic value of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic solid tumors. Clinical and biological data for patients with metastatic solid tumors treated in an oncology outpatient department and prospectively followed by a call center (PROCHE program) between January 2008 and December 2011 were analyzed. All patients with an NLR value within 28 days before the first cycle of first-line of chemotherapy were included (cohort 1). To assess influence of chemotherapy line on NLR prognostic value, data from patients treated with later chemotherapy lines were also analyzed (cohort 2). Adjusted multivariate Cox regressions with or without non-linear and time-dependent effects were performed. Optimal NLR cut-off was investigated by time-dependent sensitivity analysis using several indices. There were 317 and 134 patients in cohorts 1 and 2, respectively. Elevated NLR was associated with worse survival (hazard ratio [HR] for death, 1.35 [95% confidence interval 1.19-1.54]; p<0.0001). The optimal NLR cut-off in cohort 1 was dependent on index used and time of assessment: HR values were non-significant at a cut-off of 3.0 (1.34 [0.99-1.32], but significant when the cut-off was 4.0 (1.53 [1.11-2.10]). NLR was linearly related to mortality risk; in subgroup analysis, no significant interaction was found with co-variables or tumor localization overall (cohorts 1+2). Pre-treatment NLR is a useful prognostic tool in patients with metastatic solid tumors, irrespective of primary tumor site, chemotherapy line, age, gender and performance status. However, using an NLR cut-off value for clinical decision-making requires extreme caution.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1

Fig 1. Survival probability for patients with a neutrophil-to-lymphocyte ratio (NLR) at the cut-off value or higher versus below the cut-off value for each unit variation of NLR cut-off (Cox univariate model).

Fig 2

Fig 2. Sensitivity analysis of the neutrophil-to-lymphocyte ratio (NLR) cut-off using 4 different indices.

Using the log-rank test-base method, the NLR cut-off value displaying the greatest stability over time was determined to be between 4.0 and 4.5.

Fig 3

Fig 3

Subgroup analysis illustrating the impact of the choice of neutrophil-to-lymphocyte ratio (NLR) cut-off value; examples with NLR ≥3.0 (A) and NLR ≥4.0 (B). The model was adjusted for age, sex, disease site and European Co-operative Oncology Group performance status, and the interaction test remained statistically non-significant across the different subgroups, irrespective of the cut-off value, in favour of a persisting negative effect of a high NLR value on prognosis. *Likelihood-ratio txt for interaction of term with NLR cut-off = 3.

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