Dynamic Prognostic Nutritional Index With Circulating Tumor DNA Predicts Survival in Localized Pancreatic Ductal Adenocarcinoma.

BACKGROUND AND

OBJECTIVES

To evaluate the prognostic significance of baseline and longitudinal changes in prognostic nutritional index (PNI) in localized pancreatic ductal adenocarcinoma (PDAC) and to assess the complementary prognostic value of PNI with tumor burden measured by circulating tumor DNA (ctDNA).

METHODS

We analyzed 127 patients with localized PDAC enrolled in a prospective biomarker study (2020-2024). Laboratory values were collected at five standardized timepoints. PNI was calculated as (10 × albumin) + (0.005 × lymphocyte count). KRAS ctDNA was assessed using digital droplet PCR. The primary endpoint was overall survival (OS), analyzed using Kaplan-Meier and Cox regression, with longitudinal changes assessed using Friedman testing.

RESULTS

Low PNI (< 45) at diagnosis was associated with worse OS (p = 0.043). PNI declined significantly across treatment timepoints (p < 0.001). In multivariable analysis, decline in PNI during neoadjuvant chemotherapy independently predicted worse OS (HR 1.095, 95% CI 1.042-1.152, p < 0.001). Patients with both low PNI and ctDNA positivity had a 3.64-fold increased risk of death (HR 3.64, 95% CI 1.32-10.04, p = 0.012).

CONCLUSIONS

PNI is a dynamic, clinically accessible biomarker that independently predicts survival in localized PDAC. Integration of PNI with ctDNA improves prognostic stratification by capturing both patient host vulnerability and tumor burden.