Refinement and Validation of a Diagnostic Model (GAMAD) for Early Detection of Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Most hepatocellular carcinoma (HCC) cases were at advanced stage when diagnosis established. This study is intended to establish a clinical diagnostic model GAMAD for early-stage HCC and evaluate the diagnostic efficiency the same time. This study is a multicenter prospective study. Participants including healthy control,HCC, liver cirrhosis, hepatitis and benign tumor-like lesions are consecutively recruited into the cohort. All the blood samples are collected before any treatments and will be tested in single center in order to decrease bias.

Detailed Description
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GALAD score including age, sex, PIVKA-II(DCP), Alpha-fetoprotein (AFP) and alpha-fetoprotein L3 (AFP-L3), is a serum biomarker-based panel that can aid in early detection among patients with a high risk for liver cancer. While increasing studies showed the diagnostic accuracy of AFP-L3 was not as good as that of AFP or PIVKA-II, and AFP-L3 was not significant in the multivariable model. Thus, a model with better diagnostic accuracy and more suitable for Chinese patients is needed. Here, based on a multi-locus blood-based assay targeting circulating tumor DNA methylation, we aim to develop a novel diagnostic model--GAMAD (gender, age, methylation, AFP and DCP) and validate its performance among HCC patients and those at high risk of developing HCC,such as liver cirrhosis, hepatitis patients. This is a multicenter, observational, prospective study. After giving fully informed consent, the participants will undergo the regular treatment according to NCCN guidelines.

Official Title
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Refinement and Validation of a Comprehensive Clinical Diagnostic Model (GAMAD) for Early Detection of Hepatocellular Carcinoma: A Multicenter, Prospective Study Protocol

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Diagnostic Test: GAMAD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 Establishing Diagnosis according to the European Association for the Study of Liver(EASL) criteria High risk group of developing HCC including liver cirrhosis and hepatitis under the confirmed diagnosis Able to provide sufficient and qualified blood samples for study tests No prior or undergoing cancer treatment (local or systematic) Able to provide a written informed consent Exclusion Criteria: Obstructive jaundice patients Medical history of taking warfarin With other known malignant tumors or multiple primary tumors Patients with autoimmune diseases, genetic diseases, mental diseases/ disabilities and other diseases considered unsuitable for the study by the investigator During pregnancy or lactation Recipient of blood transfusion within 3 months prior to study blood draw Insufficient qualified blood sample for study test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hepatocellular Carcinoma patients<br>Blood samples are collected before liver resection. | Diagnostic Test: GAMAD<br>* Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.<br>|
| Liver cirrhosis<br>The diagnosis of liver cirrhosis are based on triple-phase contrast enhanced computed tomography, magnetic resonance imaging. | Diagnostic Test: GAMAD<br>* Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.<br>|
| Hepatitis<br>Patients with various hapatitis. | Diagnostic Test: GAMAD<br>* Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.<br>|
| Benign tumor-like lesions<br>Benign hepatic tumors were diagnosed based on imaging findings and histological examinations after hepatic resection. | Diagnostic Test: GAMAD<br>* Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.<br>|
| Healthy control<br>The healthy control group consist of people undergoing routine medical examination. Blood samples are collected. | Diagnostic Test: GAMAD<br>* Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GAMAD | Using GAMAD calculator model to obtain the score of each group. | Day one | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GALAD | Using GALAD calculator to obtain the score of each group. | Day one | 
| circulating tumor DNA methylation | Using circulating tumor DNA methylation to obtain diagnostic value in pre-specified subgroups. | Day one | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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early detection