Association of inflammatory markers with survival in patients with advanced gastric cancer treated with immune checkpoint inhibitors combined with chemotherapy as first line treatment
Mingyu Wan, Yongfeng Ding, Chenyu Mao, Xiaolu Ma, Ning Li, Xiao Cheng, Jiong Qian, Haiping Jiang, Yulong Zheng, Luntao Wu, Lisong Teng, Nong Xu
Abstract
Background: The emergence of immune checkpoint inhibitors has changed the landscape of first-line treatment of patients with advanced gastric cancer. Currently, the prognostic significance of inflammatory markers in first-line immunotherapy combined with chemotherapy for gastric cancer is currently unclear. This study aimed to identify inflammatory markers with potential to predict treatment outcome in advanced gastric cancer patients receiving immunotherapy combined with chemotherapy. Methods: This retrospective study enrolled untreated advanced or metastatic gastric or gastro-esophageal junction cancer patients from 5 clinical trials (the clinical trial cohort) and the real world (the real-word cohort). Inflammatory markers included in the analysis included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR). Receiver operating characteristic (ROC) curves were constructed to identify optimal cut-off values. The prognostic potential of the markers was determined using Kaplan-Meier analysis, univariate and multivariate Cox-regression analyses in the clinical trial cohort and the findings were validated in the real-world cohort. Results: In the clinical trial cohort (n=45), MLR, PLR and SII were associated with PFS but not OS (All P<0.05), while dNLR was not correlated with PFS or OS. Only NLR was associated with PFS and OS and identified as an independent prognostic predictor in the univariate and multivariate analyses. The prognostic value of NLR was validated in the real-world cohort (n=55). Conclusions: NLR was a strong predictor of PFS and OS in patients with advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy. Further prospective studies are required to validate our results.