Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Biliary Tract Cancer Recurrence Surveillance

Evaluation of Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Minimal Residual Disease (MRD) Assessment and Recurrence Monitoring in Post-treatment Biliary Tract Cancer （BTC）

This is a prospective, observational, single-center study. The purpose of this study is to evaluate the efficacy of circulating tumor mitochondrial DNA (ct-mtDNA) in plasma as a biomarker for minimal residual disease (MRD) assessment and recurrence monitoring in patients with biliary tract cancer.

Biliary tract cancer (BTC) encompasses a range of malignancies including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer. While relatively rare in many high-income countries, it poses a significant health challenge in certain regions, with a rising incidence of intrahepatic cholangiocarcinoma globally. Despite recent therapeutic advancements, BTC remains an aggressive disease with a grim prognosis, characterized by a median overall survival of less than one year and a 5-year survival rate below 5%. The primary objective of this study is to evaluate the effectiveness of plasma tumor mitochondrial mutations as a biomarker for MRD assessment and recurrence monitoring in patients with BTC. The study hypothesizes that the presence and dynamics of tumor mitochondrial mutations in plasma are associated with the risk of recurrence and overall survival in BTC patients. This is a prospective, observational, single-center study conducted by the Chinese Cooperative Group of Liver Cancer (CCGLC) under the auspices of the Chinese Chapter of International Hepato-Pancreato Biliary Association. The study will involve the collection and analysis of plasma samples from patients with BTC to detect ct-mtDNA mutations before and after treatment. The primary clinical endpoint is the impact of MRD status on progression-free survival (PFS). Secondary endpoints include the influence of treatment on MRD markers, the correlation between post-treatment residual tumor molecular burden and PFS, and the ability of MRD detection to predict recurrence earlier than traditional tumor markers or imaging methods. This study seeks to contribute to the field of BTC management by providing a more precise and personalized approach to MRD assessment and recurrence monitoring. The findings have the potential to improve long-term treatment outcomes and quality of life for patients with BTC.

Inclusion Criteria:

• Histologically confirmed biliary tract cancer (BTC);
• Expected survival time of 12 weeks or more;
• Signed informed consent form and ability to comply with the study visits and related procedures as stipulated in the protocol.

Exclusion Criteria:

• Patients with other active tumors or severe complications;
• Insufficient tumor tissue for MRD detection.