Clinical trial NCT05393102: Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome Signatures
Official title: Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome SignatuRes (GUDIER): an Observational Cohort Trial
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Focal Liver Lesions
Keywords: hepatocellular carcinoma
liver nodules
auxiliary diagnosis
liquid biopsy
peripheral blood
cfDNA
Lead sponsor: The Second Affiliated Hospital of Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: Eastern Hepatobiliary Surgery Hospital
name: Nanfang Hospital, Southern Medical University
First posted: 2022-05-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Four hundreds eligible participants will be recruited from medical centers and assigned into three groups, including participants with malignant or benign liver nodules，and participants with uncertain liver nodules.

Brief summary: As a prospective, multi-center study, GUIDER will recruit 400 liver nodules participants from different provinces and regions across China. Except for cfDNA signatures, serum biomarkers, histopathological biopsy and enhanced MRI will also be performed. The sensitivity and specificity of the cfDNA signature based-model in liver nodules diagnosing will be evaluated.

Detailed description: Patients with liver nodules will be recruited for 1 year. Peripheral blood samples of all participants will be collected after being informed about the study and potential risks. CfDNA extraction, library construction, and whole genome sequencing will be performed. A machine learning method will be implemented for cfDNA signatures-based model construction at the end of the study. Sensitivity and specificity will be used to evaluate the performance of cfDNA signatures-based model in liver nodules diagnosis.

Eligibility criteria: Inclusion Criteria:

* Eighteen years or elder；
* Participants underwent enhanced MRI for the evaluation of liver nodules ≤5 cm；
* Participants whose platelet count ≥ 50×109/L, prothrombin activity (PTA) ≥ 60%；
* Participants who are willing and able to perform hepatectomy or tissure biopsy.

Exclusion Criteria:

* Participants with different enhancement mode liver nodules that detected by enhanced MRI and without CEUS confirmation；
* Diagnosis of malignant tumors before recruitment；
* Anti-tumor therapy before recruitment ；
* HIV infection；
* Pregnancy；
* Allogenic blood transfusion or cell therapy within 14 days before peripheral blood samples collection;
* Participants with hepatic encephalopathy, hemangioma, ascites, gastrointestinal bleeding, jaundice, liver failure, congestive heart failure, or any other serious diseases that causing organ damage.
* Participants with any other factors that may leading to termination of the study.

Primary outcomes:
measure: Sensitivity of the cfDNA whole-genome signatures based model in liver nodules diagnosis.
timeFrame: Enrollment of the first participant up to 18 months
measure: Specificity of the cfDNA whole-genome signatures based model in liver nodules diagnosis.
timeFrame: Enrollment of the first participant up to 18 months
Secondary outcomes:
measure: Specificity of the model that composed of cfDNA signatures, imaging examination，serum protein markers and clinical characteristics in liver nodules diagnosis.
timeFrame: Through study completion，an average of 18 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The 2nd affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Shanghai
country: China
facility: Eastern Hepatobiliary Surgery Hospital
state: Shanghai
Study officials:
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: Hong Ren, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eastern Hepatobiliary Surgery Hospita
name: Hongyang Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanfang Hospital, Southern Medical University
name: Jinlin Hou, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kobayashi M, Ikeda K, Hosaka T, Sezaki H, Someya T, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis. Cancer. 2006 Feb 1;106(3):636-47. doi: 10.1002/cncr.21607.
citation: Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN, Khitrov G, Zhang W, Villanueva A, Battiston C, Mazzaferro V, Bruix J, Waxman S, Friedman SL. A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology. 2006 Dec;131(6):1758-67. doi: 10.1053/j.gastro.2006.09.014. Epub 2006 Sep 19.
citation: Chen L, Abou-Alfa GK, Zheng B, Liu JF, Bai J, Du LT, Qian YS, Fan R, Liu XL, Wu L, Hou JL, Wang HY; PreCar Team. Genome-scale profiling of circulating cell-free DNA signatures for early detection of hepatocellular carcinoma in cirrhotic patients. Cell Res. 2021 May;31(5):589-592. doi: 10.1038/s41422-020-00457-7. Epub 2021 Feb 15. No abstract available.