A Study of Chromosomal Abnormalities as a Predictor of Staging and Prognosis in Patients With Liver Cancer

Hepatocellular Carcinoma Clinical Trial

Official title:

A Prospective Study of Early Warning and Predictive Indicators Related to the Individualized Staging and Prognosis in Liver Cancer Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05371873
• Other study ID #: HCCpredictor
• Status: Active, not recruiting
• Start date: March 1, 2021
• Est. completion date: March 1, 2025

Study information

• Verified date: September 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Liver cancer is one of the most common malignant tumors worldwide with high morbidity and mortality, and hepatocellular carcinoma (HCC) is the main histological subtype. So far, liver resection is the most effective treatment but the postoperative recurrence rate is high at five years, and the prognosis is difficult to estimate. Microvascular invasion (MVI) and postoperative minimal residual disease (MRD) are crucial prognostic factors for patients undergoing hepatectomy. Although many laboratory and imaging methods have been established to estimate the recurrence risk, their stability and accuracy are still not high. To date, no unified conclusion is achieved. It's eagerly to screen out a batch of individualized staging and prognosis-related biological indicators for early warning and prediction of prognosis, having good stability and high precision. Circulating cell-free DNA (cfDNA) molecular detection technology is an emerging detection technology of tumor gene profiling in recent years, which can be used to predict and monitor tumor recurrence. In this study, by detecting genomic chromosomal abnormalities in plasma and tumor tissues of patients before and after surgery, the investigators hope to construct a preoperative MVI prediction model and a postoperative MRD monitoring model, so as to provide reference for the precise treatment of HCC.

Description:

MVI and MRD confirmed by postoperative pathology are important prognostic factors for recurrence after liver resection, but current assessment methods have low sensitivity and specificity. cfDNA refers to the partially degraded endogenous DNA in the circulating blood that is free from the extracellular part of the body. When derived from dead and lysed tumor cells, it is called ctDNA, having a high chromosomal instability and relating to the tumor subtype and process. By low coverage whole genome sequencing, cfDNA and ctDNA in plasma were extracted and sequenced and chromosomal instability analysis is realized through UCAD pipeline. Therefore, the investigators can predict the trend of tumor by detecting cfDNA in patients, indicate MVI and MRD, carry out individualized staging of patients, predict recurrence and prognosis, and verify the prediction efficiency through follow-up, so as to establish corresponding prediction models.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 18 to 80 years old;
• clinical diagnosis of liver cancer;
• intend to perform surgical treatment;
• postoperative pathological diagnosis of hepatocellular carcinoma;
• signed informed consent.

Exclusion Criteria:

• Not diagnosed with liver mass;
• Not undergo liver resection;
• Postoperative pathological diagnosis of non-hepatocellular carcinoma;
• Under the age of 18 or over 80;
• Concomitant pregnancy;
• Concomitant serious complications, including end-stage lung disease, unstable coronary heart disease or congestive heart failure grade 3-4, chronic kidney disease stage 4-5, cirrhosis (Child-Pugh) grade C, immunodeficiency;
• Incomplete data records.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Neoplasms

Intervention

Procedure:
• Liver resection method
undergo anatomical or non-anatomical resection of liver cancer

Locations

Country	Name	City	State
China	The First Affiliated Hospital,College of Medicine,Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (6)

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. d — View Citation

Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. No abstract available. — View Citation

Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S, Makuuchi M. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepa — View Citation

Pote N, Cauchy F, Albuquerque M, Voitot H, Belghiti J, Castera L, Puy H, Bedossa P, Paradis V. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol. 2015 Apr;62(4):848-54. doi: 10.1016/j. — View Citation

Wang D, Xu Y, Goldstein JB, Ye K, Hu X, Xiao L, Li L, Chang L, Guan Y, Long G, He Q, Yi X, Zhang J, Wang Z, Xia X, Zhou L. Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma. Liver Int. 2020 — View Citation

Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. Mol Cancer. 2019 Jul 3;18(1):114. doi: 10.1186/s12943-019-1043-x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MVI model	Establish a preoperative prediction model of MVI by detecting chromosomal abnormalities in peripheral blood cfDNA	4 years
Primary	MRD monitor	Monitor postoperative MRD in postoperative patients and predict the recurrence risk and prognosis by detecting chromosomal abnormalities in peripheral blood cfDNA.	4 years