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

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.

• Circulating tumor mtDNA (MRD Marker) [Срок оценки: Blood samples for MRD marker assessment will be collected at baseline (immediately before treatment) and at 3-7 days post-treatment.]
• Correlation Between Post-treatment MRD and PFS [Срок оценки: Residual tumor molecular burden will be assessed at the time of post-treatment blood sample collection (3-7 days post-treatment), with PFS being measured from baseline to the first occurrence of disease progression or death, up to 2 years post-treatment.]
• Early Detection of Recurrence Through MRD Monitoring [Срок оценки: MRD monitoring will be conducted at regular intervals post-treatment, with the earliest detection of recurrence being the primary focus within the two-year follow-up period (e.g., every 3 months).]
• Comparison of MRD Detection with Tumor Markers for Early Recurrence Detection [Срок оценки: Tumor marker levels and MRD status will be assessed at 3-month intervals post-treatment for up to two years, with the timing of abnormal rises being the critical comparison point.]
• Comparison of MRD Detection with Imaging for Early Recurrence Detection [Срок оценки: Imaging for disease progression will be performed at 3-month intervals or as clinically indicated (up to 2 years), with ctDNA levels being monitored in parallel to determine the lead time of MRD detection over imaging.]
• Association of mtDNA Mutational Profile with Clinicopathological Features [Срок оценки: The association will be analyzed at baseline and throughout the study duration (up to 2 years), with specific evaluations at 3-month intervals.]
• Impact of Maintenance Therapy on Negative MRD Detection Rate [Срок оценки: Assessment of the impact of maintenance therapy on MRD detection rate will be conducted at follow-up visits where MRD testing is performed at 6-month intervals after the initial treatment phase for up to two years.]