Trial Title:
A Prospective Study on the Application of Liquid Biopsy in the Surveillance of High-risk Population of HCC.
NCT ID:
NCT06134973
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma, Hepatocellular
Conditions: Keywords:
Hepatocellular Carcinoma
Liquid biopsy
ultrasonic testing
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
ultrasonic testing
Description:
ultrasonic testing
Arm group label:
Macronodular group
Arm group label:
Nodular group
Summary:
Liquid biopsy technology based on high-throughput sequencing can detect trace signals in
the early stage of cancer in plasma free DNA, so it has become a new technology suitable
for tumor diagnosis and screening.Relying on the key discipline of digestive liver
disease in our hospital, this project cooperated with BGI to jointly carry out a
prospective study on the application of liquid biopsy in the monitoring of population at
risk of liver cancer by taking advantage of its technical advantages in next-generation
sequencing, so as to provide an innovative way for the prevention and treatment of
Hepatocellular Carcinoma.
Detailed description:
Hepatocellular Carcinoma (HCC)is one of the cancers with high morbidity and mortality in
the world , and the incidence of liver cancer in China is particularly serious. In 2020,
there will be 410,000 new cases of liver cancer in China, accounting for 42.5% of the
world. There were 391,000 deaths, ranking fifth in the incidence of malignant tumors and
second in the fatality rate . Most patients with primary liver cancer have insidious
onset and have reached the middle and late stage when diagnosed. At this time, the
treatment of liver cancer is few, the prognosis is poor, and the mortality is high.Early
detection and treatment are of great significance to improve the survival rate of
patients with liver cancer, and the 5-year survival rate after early liver cancer (BCLC
stage 0/A) can reach more than 60%. However, the diagnosis rate of early liver cancer in
China is only 30%. In other countries, early diagnosis rates can be increased to more
than 60% by monitoring high-risk populations. It can be seen that close monitoring of the
pre-cancer stage is the key to early diagnosis and early treatment of HCC.
Identifying people at high risk for cancer development is the premise of cancer
Surveillance and the biggest difference from conducting tumor Screening in the general
population. Compared with many other common cancers, Targets for liquid biopsies come in
many forms, including genetics-based tests for gene mutations, and epigenetic-based tests
for methylation. Since no specific gene mutation events directly related to cancerization
have been found in liver cancer, the effect of searching for biomarkers along this route
is limited. Therefore, detecting early liver cancer from the epigenetic level has become
another way worth exploring.
In the epigenetic mechanism, DNA methylation is an important gene regulation mode, which
is closely related to the occurrence and development of tumors. More importantly,
abnormal methylation of cancer-related genes often occurs in the early stage of cancer
development, so DNA methylation signals are considered as potential markers for early
tumor screening [14]. In addition, methylation modification is tissue-specific in
different tumors and can even be used to locate the primary tissue of cancer, which is an
ideal molecular marker for tumor early screening [15]. Therefore, ctDNA, which carries
tumor cell-specific methylation information, can be used as a target for liquid biopsy of
liver cancer, providing an innovative path for early diagnosis of HCC develops gradually
on the basis of clear causes, such as typical hepatitis, cirrhosis to liver cancer "three
steps". These characteristics determine the target population for early diagnosis of HCC,
which can be found in the medical treatment of various chronic liver diseases. Making
full use of these precancerous risk factors and identifying high-risk groups of liver
cancer as surveillance objects will help improve the detection rate of cancer and obtain
a better benefit-cost ratio.
Intrahepatic nodules are the disorder of hepatic trabecular arrangement caused by fibrous
tissue hyperplasia. Their formation indicates the progression of liver injury and is also
an important stage of precancerous lesions. Pathologically, nodules can be divided into
stages such as regenerated nodules, low grade and high grade atypical hyperplasia, and
adenoma according to their proximity to cancer, but the standards and terminology are
still difficult to be unified, and pathological diagnosis requires obtaining samples
through liver puncture, which is not widely used in clinical practice. In this case, the
size of the intrahepatic nodules detected by ultrasound becomes an important basis for
liver cancer risk stratification. Taking the current guidelines for diagnosis and
treatment of liver cancer in China as an example, whether the nodule diameter is greater
than 2 cm is the main basis for classification and diagnosis: for nodules less than 2 cm,
at least two imaging evidences are required to confirm liver cancer; For nodules larger
than 2 cm, only one item is needed. In addition, stratified analysis based on the size of
intrahepatic nodules is also a framework for objective evaluation of the role of tumor
markers. Alpha-fetoprotein (AFP), a traditional serum marker for hepatocellular
carcinoma, has a sensitivity of 72-87% in advanced hepatocellular carcinoma. But for
early-stage liver cancer smaller than 2 cm, its sensitivity is only 30-50%.
In view of the shortcomings of traditional serological markers with few types and low
specificity, many important advances have been made in the application of molecular
detection techniques based on omics to cancer diagnosis and screening. The liquid biopsy
technology based on high throughput sequencing can detect specific abnormal signals in a
small amount of Circulating Tumor DNA (ctDNA) in human peripheral blood, thus promoting
the technological innovation of tumor early screening.
Targets for liquid biopsies come in many forms, including genetics-based tests for gene
mutations, and epigenetic-based tests for methylation. Since no specific gene mutation
events directly related to cancerization have been found in liver cancer, the effect of
searching for biomarkers along this route is limited. Therefore, detecting early liver
cancer from the epigenetic level has become another way worth exploring.
In the epigenetic mechanism, DNA methylation is an important gene regulation mode, which
is closely related to the occurrence and development of tumors. More importantly,
abnormal methylation of cancer-related genes often occurs in the early stage of cancer
development, so DNA methylation signals are considered as potential markers for early
tumor screening . In addition, methylation modification is tissue-specific in different
tumors and can even be used to locate the primary tissue of cancer, which is an ideal
molecular marker for tumor early screening . Therefore, ctDNA, which carries tumor
cell-specific methylation information, can be used as a target for liquid biopsy of liver
cancer, providing an innovative path for early diagnosis of HCC.
Although liquid biopsy shows promising application in the early diagnosis of HCC, most
results are based on retrospective studies. According to the steps of marker research and
development, future and multi-center studies are needed to verify it. In this project, we
will rely on the team and work foundation of the key discipline of digestion (Liver
disease), and cooperate with BGI Shenzhen BGI Medical Laboratory to carry out liquid
biopsy based on methylation, and evaluate its feasibility for liver cancer monitoring
through prospective studies. Promote the realization of early detection, diagnosis and
treatment of HCC.
The risk assessment model of liver cancer was established to identify the high-risk
groups of liver cancer. A prospective cohort study was conducted to evaluate the
predictive ability of liquid biopsy technology for liver cancer occurrence, and to verify
the performance and application prospects of this novel genetic detection technology in
liver cancer monitoring.
Criteria for eligibility:
Study pop:
Enrollment criteria: All patients who were admitted to our hospital over 18 years old and
found intrahepatic nodules by abdominal ultrasound and consented to join the prospective
cohort study of intrahepatic nodules monitoring. Enrolled patients were grouped according
to the maximum diameter of nodules in the live and were divided into nodular group
(diameter less than 2 cm) and macronodular group (diameter 2-3 cm).
Outcome events: Intrahepatic nodules were diagnosed as cancerous nodules. Follow-up:
Patients who found intrahepatic nodules but were not confirmed by imaging or pathology
were followed up every 2-3 months with imaging combined with serum AFP levels until the
outcome events were observed.
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
1. Patients diagnosed as chronic liver disease, including but not limited to chronic
hepatitis B, chronic hepatitis C, fatty liver;
2. Intrahepatic nodules detectable by ultrasound;
3. Unlimited number of nodules;
4. The patient has signed an informed consent form.
Exclusion Criteria:
1. Previously diagnosed malignant tumors；
2. Patients who are unable to cooperate with venous blood sampling；
3. According to the judgment of the investigator, the participants are not suitable to
participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
王芳
Address:
City:
Tianjin
Zip:
300170
Country:
China
Status:
Recruiting
Contact:
Last name:
Fang Wang, doctor
Phone:
+8618649047892
Email:
yaoywang@163.com
Start date:
September 1, 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Tianjin Third Central Hospital
Agency class:
Other
Collaborator:
Agency:
BGI, China
Agency class:
Other
Source:
Tianjin Third Central Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06134973
