Host determinants of adjuvant chemotherapy feasibility and survival in localized upper gastrointestinal adenocarcinoma.

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Background: Perioperative chemotherapy improves survival in resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma; however, many patients fail to initiate postoperative therapy in routine practice. Host-related determinants of adjuvant treatment feasibility and survival remain incompletely defined. Methods: We conducted a retrospective cohort study of patients with localized gastric or GEJ adenocarcinoma treated with perioperative chemotherapy and curative-intent resection at the McGill University Health Centre (2006-2025). The primary outcome was adjuvant chemotherapy initiation. Overall survival (OS) was analyzed using Kaplan-Meier and Cox proportional hazards models; prespecified 3-month landmark analyses were performed to mitigate immortal time bias. Sequential multivariable logistic models evaluated tumor variables, host factors (age, ECOG, serum albumin), and postoperative inflammatory recovery (ΔlogNLR), with incremental discrimination assessed by AUC. Results: Among 248 patients (median age 64; 85% male), 168 (67.7%) initiated adjuvant chemotherapy, which was associated with improved OS (HR 0.45; 95% CI, 0.33–0.62), including in landmark analyses. Pathology-only modeling showed modest discrimination (AUC 0.66). Addition of host factors improved discrimination (AUC 0.75); increasing age was independently associated with lower odds of initiating adjuvant therapy (OR 0.94 per year; 95% CI, 0.89–0.98), whereas higher serum albumin was independently associated with greater odds of initiation (OR 1.09 per g/L; 95% CI, 1.01–1.18). In a prespecified nested analysis among 69 patients with available longitudinal inflammatory data, model discrimination improved sequentially from AUC 0.65 to 0.77 to 0.80 with addition of host factors and ΔlogNLR. Tumor factors and chemotherapy regimen were not independently associated with adjuvant initiation after adjustment. Conclusions: In localized upper gastrointestinal adenocarcinoma, postoperative chemotherapy feasibility and survival are more strongly associated with host factors and recovery than with tumor pathology or regimen selection. These findings support perioperative optimization strategies, including nutritional support, prehabilitation, and interventions targeting systemic inflammation, to improve treatment delivery. Incorporating host vulnerability into risk stratification may refine treatment planning beyond pathological response alone. Prospective validation of dynamic inflammatory biomarkers and targeted host-directed interventions is warranted to determine whether improving treatment feasibility translates into survival benefit.