Prognostic value of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with non-small cell lung cancer receiving immune checkpoint inhibitors: a meta-analysis

Objectives Derived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs. Design This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources PubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. Eligibility criteria (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves. Data extraction and synthesis Two investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran's Q test and I-2 statistics. Publication bias of studies was assessed by Begg's test and Egger's test. We used V.12.0 of the Stata statistical software. Results This analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg's test and Egger's linear regression test. Conclusions This meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings. PROSPERO registration number CRD42021214034.

Automated summary

This study evaluated the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs through systematic review and meta-analysis. The results showed that higher dNLR levels significantly predicted poor overall survival and progression-free survival in NSCLC patients.