Integrating tumor volumetry and liquid biopsy: a New model to define prognosis in advanced pancreatic ductal adenocarcinoma.

BACKGROUND

Tumor volumetry and liquid biopsy are emerging tools reflecting tumor burden and enhancing prognostic assessment in advanced pancreatic ductal adenocarcinoma (PDAC).

METHODS

This retrospective monocentric study of 102 advanced PDAC patients assessed the prognostic value of total tumor volume (TTV), measured on CT-scans, and circulating tumor fraction (TF) at diagnosis. Liquid biopsy provided the TF and variant allele frequency (VAF) of mutations. All cutoff values were determined by maximizing Youden's index. Overall survival (OS) was analyzed using Kaplan-Meier and Cox models. Patients were stratified into high and low TTV groups according to the TTV threshold; the same approach was applied to TF. A composite prognostic score integrating TTV and TF categories stratified patients into high- and low-risk OS groups. Pearson and Spearman coefficients assessed correlations between TTV, TF, and VAFs.

RESULTS

Among 102 patients (7927 lesions manually annotated), patients in high TTV group had a significantly shorter OS than those in low TTV group (cutoff ≥ 211 cm3, HR=1.78, p = 0.02). Similarly, patients in high TF group had a significantly shorter OS than those in low TF group (cutoff ≥ 5%, HR=1.84, p = 0.01). The combined TTV-TF score showed the strongest prognostic value (HR=2.09, p < 0.005). Furthermore, TTV correlated with TF (Spearman r = 0.70), TP53 VAF (Pearson R2=0.49) and KRAS VAF (Spearman r = 0.54).

CONCLUSIONS

Early integration of tumor volumetry and ctDNA profiling refines advanced PDAC prognosis. The combined TTV-TF score offers greater prognostic value than either parameter alone, to be validated in a larger prospective cohort.