Metabolic predictors of chemotherapy response in pancreatic cancer

INTRODUCTION: Chemotherapy response in pancreatic cancer (PC) varies and is monitored by CA 19-9. Since PC is linked to metabolic dysregulation, this study evaluates how patient baseline metabolic status (glucose, HbA1c, and BMI) relates to the longitudinal trend of CA 19-9 over six months in non-surgical PC patients. METHODS: A TriNetX-based study design was employed to analyze longitudinal CA 19-9 trends over six months (representing the optimal chemotherapy response window) in PC patients who did not undergo surgical intervention. Patients were categorized into distinct strata based on (1) glucose levels: <150 mg/dL, 150-250 mg/dL, 251-350 mg/dL; (2) HbA1c levels: <7%, 7-10%, 10%-13.5%; and (3) BMI ranges: 20-25, 25-30, 30-35, 35-40. RESULTS: For Glucose: Baseline CA 19-9 levels correlated positively with increasing glucose strata. Only the highest glucose group (251-350 mg/dL) showed a statistically significant CA 19-9 reduction during chemotherapy (p<0.05). Significant differences emerged when comparing this group to both lower groups (p<0.05). Across disease stages, higher glucose levels were consistently associated with greater CA 19-9 declines, indicating enhanced chemotherapy response. This association was most pronounced in locally advanced stages (2,3). For HbA1c: Baseline CA 19-9 values were lower in the high HbA1c group (10%-13.5%). Although within-group declines were not significant, between-group comparisons at six months indicated a significantly greater CA 19-9 reduction in the highest HbA1c group compared with both the <7% and 7-10% groups (p<0.05). For BMI: Baseline CA 19-9 levels did not differ across groups. During treatment, only the highest BMI group (35-40) demonstrated a significant decline in CA 19-9 (p<0.05), while lower BMI groups (20-35) did not. Patients with BMI 35-40 responded more favorably compared with lower BMI categories (p<0.05). CONCLUSION: This study demonstrates that baseline metabolic factors modulate chemotherapy response in non-surgical PC patients. Higher glucose and BMI, as well as elevated HbA1c, were associated with greater CA 19-9 declines during chemotherapy, suggesting that metabolic status may influence treatment efficacy. These findings highlight the need for further studies and supportive metabolic interventions to optimize chemotherapy outcomes in pancreatic cancer.