Dynamic Nutritional Decline During the Diagnostic-to-Treatment Interval Is Associated with Treatment Resilience and Survival in Unresectable Pancreatic Ductal Adenocarcinoma

Background/Objectives: Patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) are vulnerable to rapid nutritional deterioration. The clinical relevance of short-term nutritional change during the diagnostic-to-treatment interval (DTI) remains unclear. In this study, we evaluated whether a dynamic change in the Geriatric Nutritional Risk Index (ΔGNRI) during the DTI is associated with treatment tolerability, treatment continuity, and survival. Methods: This single-center retrospective study included 120 patients with histologically confirmed UR-PDAC who initiated first-line palliative chemotherapy between January 2016 and April 2024. ΔGNRI was defined as the GNRI immediately before chemotherapy minus the GNRI at the initial visit. ΔGNRI was primarily analyzed as a continuous variable, and an exploratory cut-off value of −6.8 was determined by receiver operating characteristic analysis. One-to-one propensity score matching was performed as a sensitivity analysis. Clinically significant adverse events (AEs) were defined as grade ≥3 AEs or AEs requiring treatment modification, hospitalization, or treatment discontinuation. Results: Patients in the GNRI-decreased group had more frequent clinically significant non-hematologic AEs, including gastrointestinal AEs, higher hospitalization rates due to AEs, and more frequent early treatment discontinuation. ΔGNRI remained independently associated with early treatment discontinuation and failure to transition to second-line therapy in multivariable analyses. Patients in the GNRI-decreased group also had significantly shorter times to treatment failure and overall survival. These findings were consistent in propensity score-matched analyses. Conclusions: Dynamic nutritional decline during the DTI was associated with impaired treatment resilience and poor survival outcomes in UR-PDAC. ΔGNRI may help identify patients with emerging nutritional vulnerability before chemotherapy.