Prognostic value of systemic inflammatory biomarkers in advanced gastroesophageal adenocarcinoma patients undergoing chemoimmunotherapy

Abstract Background Systemic inflammation is a key driver of cancer progression across solid tumors, including gastroesophageal adenocarcinoma (GEA). Evidence on inflammatory biomarkers in advanced GEA remains largely Asian cohort–based, while European real-world data are limited and pivotal chemoimmunotherapy trials did not report these markers. Methods This exploratory, retrospective, multicenter, real-world study included patients with advanced GEA receiving 1st-line palliative chemoimmunotherapy treated across 9 Central European cancer centers. Systemic inflammatory biomarkers [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), leucocyte-to-lymphocyte ratio (LLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow Prognostic Score (mGPS), systemic inflammatory response index (SIRI) and systemic immune-inflammation index (SII)] were analyzed according to median values before treatment initiation and the impact on progression-free (PFS) and overall survival (OS) was assessed. Results Of the 182 patients (79% male, median age: 66 years) included, 146 (80%) patients presented with advanced disease and 36 (20%) with recurrent disease. When dichotomized at the median, all systemic inflammatory ratios and indices (NLR, PLR, LLR, SIRI and SII) showed significant association with shorter PFS (HR range 1.43–1.70, all p < 0.05) and OS (HR range 1.87–2.09, all p < 0.05) in univariable analysis, whereas higher LMR was associated with longer PFS (HR 0.64, p < 0.05) and OS (HR 0.47, p < 0.05). In 118 patients (65%) with available mGPS, higher scores were associated with shorter PFS (per one point increase—HR 1.72, 95% CI 1.25–2.37) and OS (HR 1.77, 95% CI 1.26–2.49). Associations were largely consistent when analyzed as continuous variables, except for SIRI (PFS and OS) and LMR (PFS). Due to missing data and overlapping indices, analyses were restricted to univariable associations. Conclusion In this European real-world cohort of advanced GEA patients receiving first-line chemoimmunotherapy, all investigated systemic inflammatory biomarkers were associated with survival in univariable analyses when dichotomized at the median. These findings support inflammatory biomarkers as readily available prognostic markers but warrant further validation, particularly regarding their associations with established clinical prognostic factors and their independent prognostic value.