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Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy

2016; Elsevier BV; Volume: 70; Issue: 2 Linguagem: Inglês

10.1016/j.eururo.2016.02.033

1873-7560

Arnoud J. Templeton, Jennifer J. Knox, Xun Lin, Ronit Simantov, Wanling Xie, Nicola Jane Lawrence, Reuben Broom, André P. Fay, Brian I. Rini, Frede Donskov, Georg A. Bjarnason, Martin Smoragiewicz, Christian Kollmannsberger, Ravindran Kanesvaran, Nimira Alimohamed, Thomas Hermanns, J. Connor Wells, Eitan Amir, Toni K. Choueiri, Daniel Yick Chin Heng,

Pancreatic and Hepatic Oncology Research

Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies. Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma. Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC cohort) and 4350 patients from 12 prospective randomized trials (validation cohort). Targeted therapies for metastatic renal cell carcinoma. NLR was examined at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values at baseline. Higher NLR at baseline was associated with shorter OS and PFS (Hazard Ratios [HR] per 1 unit increase in log-transformed NLR = 1.69 [95% confidence interval {CI} = 1.46–1.95] and 1.30 [95% CI = 1.15–1.48], respectively). Compared with no change (decrease < 25% to increase < 25%, reference), increase NLR at Week 6 by 25–50% and > 75% was associated with poor OS (HR = 1.55 [95% CI = 1.10–2.18] and 2.31 [95% CI = 1.64–3.25], respectively), poor PFS (HR = 1.46 [95% CI = 1.04–2.03], 1.76 [95% CI = 1.23–2.52], respectively), and reduced objective response rate (odds ratios = 0.77 [95% CI = 0.37–1.63] and 0.24 [95% CI = 0.08–0.72], respectively). By contrast, a decrease of 25–50% was associated with improved outcomes. Findings were confirmed in the validation cohort. The study is limited by its retrospective design. Compared with no change, early decline of NLR is associated with favorable outcomes, whereas an increase is associated with worse outcomes. We found that the proportion of immune cells in the blood is of prognostic value, namely that a decrease of the proportion of neutrophils-to-lymphocytes is associated with more favorable outcomes while an increase had the opposite effect.