Correlation between circulating tumor DNA quantity assessed by methylated markers and tumor volume in patients with metastatic pancreatic adenocarcinoma.

Circulating tumor DNA (ctDNA) is a promising marker with a strong prognostic value in metastatic pancreatic ductal adenocarcinoma (mPDAC). However, ctDNA is not detected in about a third of patients with mPDAC. The objective of this study was to assess the correlation between ctDNA and tumor volume (TV). In this monocentric cohort of mPDAC patients naïve for chemotherapy, ctDNA quantity at baseline was assessed by droplet-based digital PCR targeting two methylated markers (HOXD8 and POU4F1). TV was measured in 3D, for the primary lesion and the metastatic sites, from baseline thoraco-abdomino-pelvic computed tomography (CT) scan. Among the 71 included patients, ctDNA was detected in 47 patients (66.2%). There was a significant correlation of total and liver TV with ctDNA quantity, with Spearman's ρ of 0.353 (p = 0.01) and 0.500 (p < 0.001), respectively. Total and liver TV were higher in patients with detected ctDNA (129.5 vs 31.8 mL, p = 0.002 and 18 vs 1 mL, p < 0.001, respectively). Total and liver TV thresholds of 90.1 and 3.7 mL were associated with ctDNA detection, respectively. This study demonstrates the correlation between ctDNA and TV in mPDAC, especially for liver metastases. It supports the data that ctDNA could be a surrogate marker of TV in patients with mPDAC and liver metastases.