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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Liver Cancer, Liver Cirrhosis

Intervention / Treatment
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* Diagnostic Test: Immediate CEUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are at high risk of HCC. The ages of patients are between 18 and 80. Patients are with solid liver lesion(s) ≤ 2 cm detected by US. Patient signs the informed consent. Exclusion Criteria: 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. Patient's age is < 18 years old or > 80 years old. Patients with known hypersensitivity to CEUS, CECT, CEMRI, or hepatobiliary-specific MRI contrast agents. Patient is a pregnant or breastfeeding woman. Patient is not diagnosed based on the reference diagnostic criteria required by the study. Patient is considered to be unsuitable to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate CEUS group<br>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<br>* Subjects will receive CEUS examination immediately for the suspicious lesion detected by US.<br>|
| No Intervention: Current clinical procedure group<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Cancer, CEUS, Diagnostic Methods, Cost Optimization