Diagnosis of Nodules ≤2 cm Based on US and CEUS Compared With Current Clinical Procedure

Screening and Diagnosis of Nodules ≤2 cm in High-risk HCC Patients in China Based on US and CEUS: a Multicenter, Prospective, Randomized Controlled Study

Due to different etiologies, diagnosis and treatment of HCC in China is different from that in Western countries.US is an important screening method for HCC in patients with liver cirrhosis. CEUS, as an enhanced imaging method based on US, has the advantages of convenience, non-radiation, low cost, short examination time, and the diagnostic performance of HCC is comparable to that of CECT, CEMRI, and hepatobiliary-specific MRI.

It is of great significance to consider the cost-effectiveness of each examination based on the principle of cost minimization. Therefore, we propose immediate CEUS examination for suspicious lesions ≤2 cm screened by US, and determine the diagnostic process of further diagnostic methods based on the CEUS results. The aim of this study is to establish a screening and diagnosis process for HCC ≤2 cm suitable for China considering time effect, economic effect and diagnostic efficiency.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Liver Cancer
• Intervention / Treatment: Diagnostic test: Immediate CEUS

• Study Type: Interventional
• Enrollment (Anticipated): 6730
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300170
      • Recruiting
      • Tianjin Third Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients are at high risk of HCC.
2. The ages of patients are between 18 and 80.
3. Patients are with solid liver lesion(s) ≤ 2 cm detected by US.
4. Patient signs the informed consent.

Exclusion Criteria:

1. Patients are with liver cirrhosis due to congenital hepatic fibrosis or due to hepatic vascular diseases such as hereditary telangiectasia, Budd-Chiari syndrome, chronic portal vein occlusion syndrome, congestive heart disease.
2. Patient's age is < 18 years old or > 80 years old.
3. Patients with known hypersensitivity to CEUS, CECT, CEMRI, or hepatobiliary-specific MRI contrast agents.
4. Patient is a pregnant or breastfeeding woman.
5. Patient is not diagnosed based on the reference diagnostic criteria required by the study.
6. Patient is considered to be unsuitable to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate CEUS group; CEUS (SonoVue) was performed immediately after routine US screening of suspicious lesions. The lesions were classified according to CEUS examination by the diagnosing physician, including consideration of HCC, suspected HCC, and benign lesions. Further hepatobiliary-specific MRI (Modis/Primexian) was performed for lesions considered HCC or suspicious for HCC, and benign lesions were followed up. The diagnostic findings of hepatobiliary-specific MRI were classified by the diagnosing physician and included consideration of HCC, suspected HCC, and benign lesions. For hepatobiliary-specific MRI lesions considered HCC or suspicious for HCC, pathological examination was performed, and benign lesions were followed up.	Diagnostic test: Immediate CEUS; Subjects will receive CEUS examination immediately for the suspicious lesion detected by US.
No Intervention: Current clinical procedure group; After the suspicious lesions were screened by routine US, CECT, CEMRI and hepatobiliary-specific MRI (the first enhanced imaging examination) were independently selected by clinicians. According to the first examination results of the contrast-enhanced image, the diagnosis was classified by the diagnosing physician, including considering HCC, suspicious HCC, and benign lesions. Another contrast-enhanced imaging examination (CECT or CEMRI or hepatobiliary-specific MRI or CEUS) was performed again for lesions considered or suspected of HCC (second contrast-enhanced imaging study), and negative lesions were followed up. According to the examination results of the second enhanced imaging, the classification includes considering HCC, suspicious HCC, and benign. Pathological examination was performed for lesions considered HCC or suspicious for HCC on the second enhanced image, and benign lesions were followed up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance based on US and immediate CEUS with current routine	The diagnostic efficacy，including sensitivity, specificity, accurary and AUC， of the two groups for HCC from the detection of suspicious lesions by routine US screening to the final diagnosis.	6 to 12 months
Time benefits based on US and immediate CEUS with current routine	Time from the detection of suspicious lesions by routine US screening to the first diagnosis of HCC by enhanced imaging examinations and the final diagnosis of HCC.	6 to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The economic benefit based on US and immediate CEUS with current routine	The cost of imaging studies from the discovery of suspicious lesions by routine US screening to the final clinical diagnosis of HCC or the clinical diagnosis of benign lesions.	6 to 12 months

Collaborators and Investigators

• Sponsor: Tianjin Third Central Hospital
• Collaborators: Shanxi Province Cancer Hospital; Hebei General Hospital; Shengjing Hospital; Tianjin Medical University Cancer Institute and Hospital; Beijing Hospital; China-Japan Friendship Hospital; Tianjin Medical University General Hospital; Tianjin Medical University Second Hospital; The First Affiliated Hospital of Shanxi Medical University; Tianjin Nankai Hospital; First Affiliated Hospital of Harbin Medical University; Second Hospital of Shanxi Medical University; The Third Affiliated Hospital of Harbin Medical University; Shanxi Provincial People's Hospital; Tianjin Second People's Hospital; Peking University Binhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 11, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Liver Cancer; CEUS; Diagnostic Methods; Cost Optimization
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Fibrosis; Liver Cirrhosis; Liver Neoplasms
• Other Study ID Numbers: drjingxiang004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No