ctDNA monitoring predicts recurrence and survival in post-surgical biliary tract cancer
Investigators evaluated a tumor-informed customized ctDNA panel for minimal residual disease assessment and longitudinal monitoring in 111 evaluable patients with resectable biliary tract cancer. Preoperative plasma sequencing detected circulating tumor DNA in 51.4% of cases, with TP53, KRAS, ARID1A, and SMAD4 mutations being most frequent, and positivity correlated with advanced pathological stage and significantly shorter relapse-free and overall survival. During postoperative follow-up, 57.8% of patients exhibited persistent or newly detectable ctDNA prior to radiological recurrence, and ctDNA positivity during monitoring strongly predicted earlier relapse (HR 9.04; 95% CI 3.56-23.97; p < 0.001). The findings demonstrate that customized liquid biopsy can reliably track molecular recurrence in biliary tract cancer, offering laboratories a validated framework for MRD surveillance and potential early intervention strategies.
The original study
Assessment of MRD and Longitudinal Monitoring of Post-Surgery Biliary Tract Cancer With a Customized ctDNA Panel.
- Authors
- Shinohara Y, Nakamura T, Kimura Y, Murakami T, Kojima S, Yamaguchi T, et al.
- Journal
- Cancer science
- Type
- Journal Article
- PMID
- 42831344
Original abstract
Biliary tract cancer (BTC) is a rare abdominal cancer with poor prognosis. Circulating tumor DNA (ctDNA) analysis with liquid biopsy offers a minimally invasive approach for cancer detection and disease monitoring. Given limited reports, this study aims to evaluate minimal residual disease (MRD) and longitudinal ctDNA monitoring in BTC patients. A total of 124 BTC patients were enrolled, with 111 evaluable for ctDNA analysis using a tumor-informed approach. Baseline tumor tissue and plasma samples were collected for comprehensive genomic profiling (CGP). A customized ctDNA panel was developed based on CGP of resectable BTC tumors and public genomic databases for MRD assessment and longitudinal monitoring. ctDNA sequencing was performed using ultradeep targeted next-generation sequencing. Associations between ctDNA detection and outcomes were analyzed. Preoperative ctDNA detection was associated with advanced pathological stage and significantly worse relapse-free survival (RFS) and overall survival. Using this ctDNA panel, preoperative ctDNA was detected in 51.4% of cases, with TP53, KRAS, ARID1A, and SMAD4 being the most frequently mutated genes. During longitudinal monitoring, 57.8% of patients showed persistent ctDNA positivity or subsequent ctDNA detection before radiological recurrence. RFS was significantly shorter among patients with ctDNA positivity during longitudinal monitoring than among those with undetectable ctDNA (HR = 9.04; 95% CI, 3.56-23.97; p < 0.001). Our customized panel detected BTC-specific mutations in plasma using liquid biopsy, and ctDNA positivity was strongly associated with recurrence and survival outcomes. This panel has the potential to improve MRD assessment and longitudinal monitoring in BTC, enabling earlier intervention and improved patient stratification.