Association of inflammatory markers with survival in patients with advanced gastric cancer treated with immune checkpoint inhibitors combined with chemotherapy as first line treatment.

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.

Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy.

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.

Prognostic Value of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Combined Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Stage IV Advanced Gastric Cancer.

Background: The prognostic value of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and the combined NLR-PLR score in patients with stage IV gastric carcinoma (GC) has not yet been clarified. Therefore, this study aimed to explore the potential association of NLR, PLR, and NLR-PLR score with the prognosis of patients with stage IV GC. Methods: This retrospective study included 466 patients with GC diagnosed between 2010 and 2017. High NLR and high PLR were defined using the median values as the cutoff values. We then combined the NLR and PLR value and generated the NLR-PLR score as a new biomarker. Patients were divided into three groups according to their NLR-PLR score. Univariate and multivariate analyses were conducted to compare survival outcomes. Results: Median overall survival (OS) and progression-free survival (PFS) were 15.5 months (range, 0.7-96.8 months) and 6.7 months (range, 0.5-30.4 months), respectively. The NLR, PLR, and the NLR-PLR scores were correlated with clinical outcomes such as OS and PFS. Median OS for patients with NLR-PLR scores of 0, 1, and 2 was 22.5, 15.7, and 11.2 months, respectively. Median PFS for patients with these NLR-PLR scores of 0, 1, and 2 was 7.8, 7.1, and 5.2 months, respectively (P < 0.001). High NLR-PLR scores predicted poor survival in patients with stage IV GC (all P < 0.05). Conclusion: Our findings provide scientific evidence to support that the NLR-PLR score may be able to independently predict survival outcomes in patients with stage IV GC.