Baseline visceral fat area and early visceral fat loss predict survival in HER2-negative advanced gastroesophageal adenocarcinoma treated with immunochemotherapy

Immune checkpoint inhibitor (ICI)-based chemotherapy has improved outcomes in human epidermal growth factor receptor 2 (HER2)-negative advanced gastroesophageal adenocarcinoma (GEA), but clinically accessible prognostic biomarkers remain limited. This study evaluated the prognostic significance of baseline and early changes in computed tomography (CT)-derived body composition and peripheral inflammatory markers in patients receiving first-line immunochemotherapy. This retrospective single-center study included 188 patients with unresectable HER2-negative advanced GEA who completed at least three treatment cycles and underwent baseline and post-cycle 3 CT and laboratory assessments. Visceral fat area (VFA), subcutaneous fat area, and skeletal muscle area were measured at the third lumbar vertebral level, and inflammatory and nutritional indices, including the neutrophil-to-lymphocyte ratio (NLR), were calculated. Associations with progression-free survival (PFS), overall survival (OS), and treatment response were assessed using Cox regression and exploratory threshold-based analyses. During a median follow-up of 16.2 months, 102 PFS events and 75 deaths occurred. In multivariable baseline analyses, a higher Charlson Comorbidity Index, elevated carcinoembryonic antigen (CEA), higher NLR, and lower VFA were independently associated with shorter PFS, whereas elevated CEA and lower VFA were independently associated with shorter OS. Each 1000-mm² increase in VFA was associated with lower risks of progression or death (hazard ratio [HR], 0.912; 95% confidence interval [CI], 0.863-0.964) and death (HR, 0.919; 95% CI, 0.864-0.977). Patients with high baseline VFA also had a higher objective response rate than those with low VFA (45.8% vs. 28.4%). In exploratory threshold-based longitudinal analyses, a VFA reduction greater than 20% was associated with shorter PFS and OS; however, continuous analyses of body composition changes did not confirm independent associations. Higher baseline VFA may represent a favorable host-related prognostic marker in HER2-negative advanced GEA treated with immunochemotherapy, whereas the prognostic value of early VFA loss requires prospective external validation.