Prognostic value of pretreatment neutrophil-to-lymphocyte ratio in advanced gastrointestinal cancer immunotherapy: evidence from published studies and a Chinese single center cohort

Abstract

BackgroundIdentification of prognostic biomarkers for outcomes in gastrointestinal (GI) cancer with immunotherapy is important. This study investigated the relationship between the prognostic biomarker, pretreatment neutrophil-to-lymphocyte ratio (preNLR), and immunotherapeutic outcomes in patients with advanced GI cancer.MethodsWe searched the PubMed, Embase, and Cochrane Library databases for studies reporting predictive values for preNLR in patients with advanced GI cancer treated with immune checkpoint inhibitor (ICI). The primary outcomes considered were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were pooled using a random effects model. We then validated the results observed in an in-house cohort of patients treated with ICIs for advanced GI cancers. Other prognostic factors for PFS and OS were explored using Cox proportional hazard analyses.ResultsOverall, 27 observational studies involving 3,610 patients with advanced GI cancer were included. Patients with higher preNLR were associated with poorer PFS (HR 1.70, 95% CI 1.50–1.92) and OS (HR 2.35, 95% CI 1.82–3.03) with ICI treatment. Subgroup analyses based on NLR cut-off value, research center, sample size, and ICI drugs used were consistent with the primary results. A retrospective analysis of the in-house patient cohort validated these results (PFS: HR 3.173, 95% CI 2.314–4.351; OS: HR 3.004, 95% CI 1.837–4.912). Multivariable Cox regression analysis of 174 patients showed that higher preNLR and negative programmed death ligand-1 (PD-L1) expression were independently, significantly, and unfavorably associated with PFS and OS.ConclusionPreNLR might be an effective prognostic biomarker for patients with advanced GI cancer treated with ICIs.