Prognostic value of neutrophil to lymphocyte ratio in gastric cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis

Background: The neutrophil to lymphocyte ratio (NLR) is a cost-effective and easily identifiable inflammatory biomarker that has been shown to be closely associated with tumor prognosis and predict survival in patients with multiple malignancies. However, the predictive value of NLR in patients with gastric cancer (GC) treated with immune checkpoint inhibitors (ICIs) has not been fully explored. Therefore, we conducted a meta- analysis to explore the potential of NLR as a predictor of survival in this population. Methods: We systematically searched the PubMed, Cochrane Library, and EMBASE databases from inception to the present for observational researches on NLR and its relationship with progression or survival in GC patients receiving ICIs. To assess the prognostic significance of NLR on overall survival (OS) or progression-free survival (PFS), we used fixed or random-effect models to derive and combine hazard ratios (HRs) with 95% confidence intervals (CIs). We also examined the relationship between NLR and treatment efficacy by calculating relative risks (RRs) with 95% CIs for objective response rate (ORR) and disease control rate (DCR) in patients with GC receiving ICIs. Results: Nine studies of 806 patients were eligible. OS and PFS data were obtained from 9 and 5 studies, respectively. In nine studies, NLR was associated with poor survival, the pooled HR was 1.98 (95% CI 1.67- 2.35, p < 0.001), indicating a significant association between high NLR and worse OS. We conducted subgroup analyses based on study characteristics to confirm the robustness of our findings. A relationship between NLR and PFS were reported in five studies with a HR of 1.49 (95% CI 0.99- 2.23, p = 0.056), which was not significantly associated. Pooling four studies that examined the correlation between NLR and ORR/ DCR in GC patients, we observed a significant correlation between NLR and ORR (RR = 0.51, p = 0.003), but no significant correlation between NLR and DCR (RR = 0.48, p = 0.111). Conclusion: In summary, this meta-analysis indicates that increased NLR is significantly linked to worse OS in patients with GC receiving ICIs. In addition, lowering NLR can improve ORR. Thus, NLR can serve as a predictor for prognosis and treatment response in GC patients treated with ICIs. Nevertheless, further high-quality prospective studies are required to verify our findings in the future.