The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials

Background: Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown. Methods: This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters. Results: The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR = 0.55, P<0.0001), ECOG (HR = 0.62, P = 0.002) and neutrophils (HR = 0.65, P = 0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P = 0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P = 0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log(10)NLR models, with an optimal NLR cutoff of 3.0. Conclusions: NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.