Dynamic Neutrophil-to-Lymphocyte Ratio Stratifies Survival and Immune-Related Adverse Events in Lung and Gastric Cancer Patients with Immunotherapy

Chengcheng Qian, Mengting Wang, Chuyi Liu, Feng Liu, Wenying Zhang, Xiaohua Hu, Yanjie Zhang, Bin Jiang, Jiongyi Wang, Ming Xu, Haihua YuanDepartment of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haihua Yuan, Department of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 280 Mohe Road, Shanghai, People’s Republic of China, Tel +86-21-56691101-7261, Fax +86-21-63136856, Email 72300611229@shsmu.edu.cn Ming Xu, Department of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 280 Mohe Road, Shanghai, People’s Republic of China, Tel +86-21-56691101-7261, Fax +86-21-63136856, Email mingxu@shsmu.edu.cnBackground: Dynamic neutrophil-to-lymphocyte ratio (NLR) has emerged as a prognostic marker in immunotherapy outcomes, yet phase-specific alterations in NLR after immunotherapy and their association with treatment efficacy remain underreported. This study aimed to clarify the prognostic utility of NLR dynamics in patients receiving immune checkpoint inhibitors (ICIs) therapy.Methods: We retrospectively analyzed 101 cancer patients (including lung and gastric cancer) treated with ICIs. NLR was measured at three time points: baseline (prior to ICIs initiation), Cycle 1 (C1, 1 month post-treatment), and Cycle 3 (C3, 3 months post-treatment). Pearson’s chi-square test and Kaplan–Meier survival analyses were used to assess associations between NLR dynamics and immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS).Results: Baseline NLR showed no significance with irAEs. However, elevated C1 NLR was related with early irAEs in both lung and gastric cancers (OR = 2.883, p = 0.029). In lung cancer patients, a reduced C3 NLR was significantly associated with longer PFS (HR = 2.376, p = 0.006) and OS (HR = 3.315, p < 0.001), whereas the association was weaker in gastric cancer (PFS: HR = 1.758, p = 0.085; OS: HR = 2.284, p = 0.019). Multivariate analysis identified C3 NLR was associated independently with both PFS and OS in lung cancer patients. Furthermore, a ≥ 30% elevation in NLR stratified patients into distinct risk categories, with the potential clinical value influenced by tumor type.Conclusion: Phase-specific NLR dynamics were correlated with distinct immunotherapy outcomes. C1 NLR was associated with early toxicity in both lung and gastric cancers, whereas sustained NLR reduction at C3 was associated with more favorable survival outcomes in lung cancer. These findings suggest that longitudinal, phase-specific NLR assessment may provide complementary information for monitoring treatment-related outcomes and requires further prospective validation.Keywords: neutrophil-to-lymphocyte ratio, immunotherapy, immune-related adverse events, biomarker, prognosis