1013TiP - Refinement and validation of a comprehensive clinical diagnostic model (GAMAD) for early detection of hepatocellular carcinoma: A multicenter, prospective study protocol

Background

Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive GAMAD test model for early HCC detection by incorporating demographic data (Gender and Age), circulating tumor DNA (ctDNA) Methylation signature in blood, and commonly utilized serum biomarkers [alpha-fetoprotein (AFP), des-γ-carboxy-prothrombin (DCP)]. Additionally, the study will evaluate the model's effectiveness among HCC patients at various stages and/or high-risk HCC groups.

Trial design

This prospective, multicenter, non-interventional study will enroll 2,000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis, and benign liver space-occupying lesions), and healthy individuals. Blood samples from all participants will be divided into training and validation sets (1,400 and 600 cases, respectively) for the development and blind validation of the GAMAD (Gender + Age + Methylation + AFP + DCP) HCC-discriminating classifier. The classifier's accuracy and utility will be further assessed in the entire cohort (training and validation cohort). Primary outcome endpoints include sensitivity, specificity, and accuracy [ROC curves; area under the curve (AUC) value] of GAMAD for HCC (in early and each stage) and/or high-risk HCC groups. Secondary outcome endpoints involve comparing GAMAD with the established GALAD model and individual blood indices (AFP, DCP, and methylation testing) to evaluate: (1) GAMAD's clinical utility and significance for HCC patients in early and other stages (according to different staging systems: TNM staging, the Milan criteria, and the BCLC staging criteria); (2) GAMAD's discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, HBV related HCC and HBV, HCV related HCC and HCV, and nonalcoholic fatty liver disease (NAFLD) related HCC and NAFLD.

Clinical trial identification

NCT05626985.

Editorial acknowledgement

Legal entity responsible for the study

Eastern Hepatobiliary Surgery Hospital and The First Hospital of Jilin University.

Funding

Singlera Genomics Inc.

Disclosure

T. Yang: Financial Interests, Institutional, Principal Investigator: Eastern Hepatobiliary Surgery Hospital. H. Liu, H. Wang, S. Zhou, Z. Zheng, R. Liu: Financial Interests, Institutional, Full or part-time Employment: Singlera Genomics Inc. F. Shen: Financial Interests, Institutional, Principal Investigator: Eastern Hepatobiliary Surgery Hospital. G. Lv: Financial Interests, Institutional, Principal Investigator: First Hospital of Jilin University. All other authors have declared no conflicts of interest.