Circulating Tumor DNA and Tissue Testing for Pancreatobiliary Tumors

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Pancreaticobiliary tumors have a poor prognosis, with tissue-based next-generation sequencing (NGS) identifying actionable alterations.
• Limitations in tissue acquisition can hinder comprehensive genomic profiling.
• Circulating tumor DNA (ctDNA) offers a less invasive alternative, but its concordance with tissue NGS requires investigation.

Purpose of the Study:

• To determine the mutation concordance rate (mCR) between ctDNA and tissue NGS for pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC).
• To evaluate ctDNA's utility as a biomarker for treatment response in PDAC.

Main Methods:

• Retrospective cohort study of 790 patients with PDAC and CC treated between 2014 and 2025.
• Patients underwent ctDNA testing (1 platform) and tissue NGS (2 platforms).
• Mutation concordance was calculated using Spearman correlation; treatment response was assessed via serial ctDNA, restaging scans, and CA19-9 levels.

Main Results:

• Significant mCR was observed between ctDNA and tissue NGS in both PDAC (Spearman correlation=0.47) and CC (Spearman correlation=0.56).
• Approximately 65% of patients showed shared gene alterations between ctDNA and tissue testing.
• In PDAC, increased ctDNA variant allele frequency of TP53 and KRAS correlated with progressive disease.

Conclusions:

• ctDNA testing demonstrates significant mutation concordance with tissue NGS in pancreaticobiliary tumors.
• ctDNA shows potential for detecting resistant clones and monitoring treatment response in PDAC.
• These findings support ctDNA as a valuable tool in managing advanced pancreaticobiliary cancers.