We aimed to explore the application of circulating
cell-free DNA (
cfDNA) profiling in monitoring
tumor burden in patients with pancreatic ductal
adenocarcinoma (PDAC). Thirty-eight patients with advanced PDAC receiving first-line
FOLFIRINOX chemotherapy were prospectively enrolled. Next-generation sequencing for a panel of 560 genes covering a wide range of
cancer-related loci was performed to profile
cfDNA. In total, 25 patients (65.8%) had at least one common driver gene alterations (KRAS, TP53, SMAD4, CDKN2A) detected within
cfDNA. In contrast, no above
tumor-related recurrent mutations were found in plasma from 13 healthy individuals. Concordant alterations in plasma
cfDNA and
tumor tissue
DNA was confirmed in two of three patients with available tissues. Further analysis showed that mutant allele fraction (MAF) for altered loci in
cfDNA correlated with
tumor stage, metastatic burden, and overall survival. Serial blood samples were collected from 17 patients after
chemotherapy. We found that allele fraction for specific altered loci declined in
chemotherapy-responding subjects. For cases who were resistant to this therapeutic regimen, increased ctDNA MAF was observed at the time of
disease progression. Meanwhile, the dynamics of total
cfDNA concentration correlated with
tumor burden following
chemotherapy. Collectively, we provide evidence that pretreatment ctDNA level correlates with
tumor burden in PDAC, and serial
cfDNA analysis is a robust tool for monitoring
cancer response to
chemotherapy.