BackgroundThe 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.MethodsThis 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.ResultsIn 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).ConclusionsNLR 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.

Background. Chemoimmunotherapy has become the first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). We aimed to compare the efficacy and toxicity of different chemoimmunotherapy combinations to determine the optimal treatment option. Methods. PubMed, Web of Science, Cochrane Library, Embase, and abstracts of recent relevant meetings were searched to identify phase III randomized controlled trials (RCTs) of first-line programmed cell death-1 (PD-1)/its receptor (PD-L1) inhibitors plus chemotherapy for ESCC up to July 2022. A network meta-analysis (NMA) following Bayesian approaches was conducted in R software. Result. Our study included six RCTs and 3,611 patients. According to the NMA, toripalimab plus chemotherapy ranked first to prolong overall survival (OS). Sintilimab plus chemotherapy and camrelizumab plus chemotherapy consistently yielded the greatest benefits regarding progression-free survival (PFS). The maximal complete response rate (CRR) and objective response rate (ORR) were achieved with nivolumab plus chemotherapy. Tislelizumab plus chemotherapy attained the highest likelihood of achieving a disease control rate (DCR). The addition of immunotherapy to chemotherapy was associated with improved survival and increased adverse events. Subgroup analysis revealed that patients with PD-L1 tumor positive score (TPS) ≥10% showed a better OS than those with lower values when undergoing first-line chemoimmunotherapy. Anti-PD-1 inhibitor with platinum plus paclitaxel (TP) regimen showed a superior PFS benefit over anti-PD-1 inhibitor with platinum plus fluorouracil (FP) regimen. Conclusion. The NMA analysis suggested that sintilimab plus chemotherapy was the preferred regimen for treatment-naive advanced ESCC patients with the best balance between efficacy and safety. Anti-PD-1 inhibitors with the TP regimen were associated with more favorable PFS than those with the FP regimen.

Background. Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy. Methods. Data of clinical features, peripheral blood parameters, and treatment records were collected in unresectable ESCC patients who received PD-1/PD-L1 inhibitors plus chemotherapy as the first-line treatment from September 2017 to August 2021. The nomogram based on MLR and clinical parameters for predicting the overall survival (OS) was developed and validated. Results. Out of 81 patients enrolled, patients with a lower MLR had significantly longer progression-free survival (PFS) and OS than patients with a higher pretreatment MLR (p = 0.0067; p = 0.00069). The OS nomogram integrating MLR, performance status (PS) score, and body mass index (BMI) achieved a C-index of 0.770 (95%CI 0.645–0.896). The area under the ROC curve (AUC) value of the nomogram predicting 12-, 18-, and 24-month OS rates were 0.855, 0.792, and 0.744, respectively, which were higher than the clinical TNM staging system or the MLR. Stratified by the nomogram-generated scores, three risk groups (low, moderate, and high) in survival curves manifested a distinct difference (p < 0.0001). Conclusion. MLR emerged as an independent predictive factor for PFS and OS in treatment-naive unresectable ESCC patients treated with chemoimmunotherapy. The constructed nomogram of MLR and clinical parameters was a reliable model for prognostic estimation.