MRI vs. Ultrasound Screening for Liver Cancer

(PREMIUM Trial)

Recruiting in Palo Alto (17 mi)

+15 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

Disqualifiers: HCC, Organ transplant, Advanced liver dysfunction, GFR <30, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The study is a randomized trial of two different screening methods for early detection of liver cancer in patients with cirrhosis of the liver. The goal of PREMIUM is to compare an abbreviated version of the diagnostic gold standard for HCC (aMRI) +AFP to the standard-of-care screening (US+AFP) in patients at high risk of developing HCC. The investigators hypothesize that HCC will be detected at earlier stages, allowing for more curative treatments and resulting in a reduction in HCC-related mortality.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the treatment Abbreviated Magnetic Resonance Imaging with serum AFP for liver cancer screening?

Research shows that using non-contrast abbreviated MRI (aMRI) with alpha-fetoprotein (AFP) is effective for detecting liver cancer, performing comparably to full MRI but without the risks of contrast media and at a lower cost. Additionally, combining AFP with ultrasound can detect liver cancer at earlier stages, which may lead to higher chances of successful treatment. ^{1 2 3 4 5}

Is MRI or Ultrasound screening for liver cancer safe for humans?

Non-contrast abbreviated MRI (aMRI) is considered safe as it avoids the risks associated with contrast media exposure, which can be a concern in full diagnostic MRI. Ultrasound is a commonly used and generally safe imaging method, though it may have lower sensitivity for detecting early-stage liver cancer. ^{1 2 5 6 7}

How does the treatment of Abbreviated MRI with AFP differ from other treatments for liver cancer screening?

Abbreviated MRI with AFP is unique because it combines a shorter, non-contrast MRI scan with a blood test for alpha-fetoprotein (AFP), offering higher sensitivity for detecting liver cancer compared to the traditional ultrasound method, without the need for contrast agents and at a lower cost than full MRI. ^{1 2 6 7 8}

Research Team

George N. Ioannou, MD MS

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Eligibility Criteria

This trial is for adults aged 18-75 with liver cirrhosis, diagnosed through biopsy or other specific medical criteria. Participants must be at high risk of developing liver cancer but cannot have had a prior diagnosis of HCC, organ transplants, severe comorbid conditions, or certain metal implants that interfere with MRI scans.

Inclusion Criteria

I am at high risk for liver cancer, aged 18-75, and can consent to treatment.

I have been diagnosed with cirrhosis through a biopsy, imaging, physical signs, or specific tests.

Exclusion Criteria

My health conditions limit my life expectancy due to a high CirCom score.

I have had an organ transplant or am waiting for one.

I have been diagnosed or suspected to have liver cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Initial Screening

Participants are randomized to either the aMRI+AFP or US+AFP screening arms and begin initial screening

6 months

1 visit every 6 months

Ongoing Screening

Participants continue with their assigned screening method (aMRI+AFP or US+AFP) every 6 months

7.5 years

1 visit every 6 months

Follow-up

Participants are monitored for mortality and other outcomes after the screening period

8 years

Treatment Details

Interventions

• Abbreviated Magnetic Resonance Imaging with serum AFP (Imaging)
• Abdominal Ultrasound Screening with serum AFP (Imaging)

Trial Overview The PREMIUM study compares two screening methods for early detection of liver cancer in high-risk patients: abbreviated MRI plus serum AFP test versus standard abdominal ultrasound plus serum AFP test. The aim is to find out if the former can detect cancer earlier and reduce mortality.

Participant Groups

Group I: Abbreviated Magnetic Resonance Imaging with serum AFP Experimental Treatment 1 Intervention

Abdominal aMRI+ serum AFP every 6 months from the time of recruitment until the end of year 8

Group II: Abdominal Ultrasound Screening with serum AFP Active Control 1 Intervention

abdominal ultrasound (US)+serum alpha fetoprotein (AFP) every 6 months from the time of recruitment until the end of year 8

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

Dynamic contrast-enhanced abbreviated MRI (Dyn-AMRI) shows similar diagnostic performance to complete MRI for detecting hepatocellular carcinoma (HCC), with both having a sensitivity of 92.8%, significantly outperforming non-contrast abbreviated MRI (NC-AMRI) which had a sensitivity of 72.3%.

Non-contrast abbreviated MRI combined with alpha-fetoprotein (AFP) testing also demonstrated comparable sensitivity to Dyn-AMRI and complete MRI, making it a viable option for HCC detection, especially since it requires no contrast medium and has a shorter acquisition time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening. Girardet, R., Dubois, M., Manasseh, G., et al.[2023]

Non-contrast abbreviated magnetic resonance imaging (aMRI) is a cost-effective method for hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, showing incremental cost-effectiveness ratios of $3,667 per quality-adjusted life year (QALY) in Thailand and $37,062 per QALY in the United States.

aMRI outperforms the combination of ultrasonography and alpha-fetoprotein (AFP) testing in cost-effectiveness, particularly in populations with higher HCC incidence, making it a valuable tool for early detection in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. Decharatanachart, P., Pan-Ngum, W., Peeraphatdit, T., et al.[2023]

Screening for hepatocellular carcinoma in patients with chronic hepatitis B using alpha-fetoprotein (AFP) or AFP plus ultrasound (AFP/US) helps detect tumors at earlier stages, which can lead to higher rates of surgical resection.

However, it remains uncertain whether this screening method actually reduces disease-specific or overall mortality rates, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the best surveillance for hepatocellular carcinoma in chronic carriers of hepatitis B? Rugge, JB., Lochner, J., Judkins, D.[2018]

In a study of 305 patients with chronic hepatitis B, incorporating serum alpha-fetoprotein (AFP) levels into the diagnostic criteria significantly improved the sensitivity for detecting subcentimeter hepatocellular carcinoma (HCC) compared to traditional imaging methods.

A new diagnostic criterion requiring at least three out of four specific findings (including AFP > 13.7 ng/mL) achieved a sensitivity of 71.6% in the derivation cohort, which was significantly higher than the traditional diagnostic hallmark sensitivity of 52.3%, while maintaining high specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic algorithm for subcentimeter hepatocellular carcinoma using alpha-fetoprotein and imaging features on gadoxetic acid-enhanced MRI. Huang, P., Wu, F., Hou, K., et al.[2023]

Abbreviated magnetic resonance imaging (AMRI) has emerged as a promising technique for liver imaging, with various protocols like noncontrast AMRI, hepatobiliary-AMRI, and dynamic-AMRI being utilized for different liver conditions.

AMRI is effective for screening and monitoring liver diseases, including hepatocellular carcinoma, nonalcoholic fatty liver disease, and liver metastases in colorectal cancer patients, highlighting its versatility in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated Liver Magnetic Resonance Imaging Protocols and Applications. Altinmakas, E., Taouli, B.[2022]

Patients prioritize higher sensitivity in screening tests for hepatocellular carcinoma, with an importance score of 39.8%, indicating that they value the ability to accurately detect cancer over other factors.

Cost and lower false-positive rates are also significant considerations for patients, with scores of 22.8% and 19.4% respectively, suggesting that affordability and test reliability are crucial for patient adherence to screening recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eliciting Patient Preferences for Hepatocellular Carcinoma Screening: A Choice-Based Conjoint Analysis. Fazeli, S., Covarrubias, Y., Bassirian, S., et al.[2022]

The MIRACLE-HCC study is a prospective trial involving 416 patients with compensated liver cirrhosis, comparing the effectiveness of noncontrast MRI versus noncontrast ultrasound for the early detection of hepatocellular carcinoma (HCC).

This study aims to determine if noncontrast MRI can detect early-stage HCC more effectively than ultrasound and whether it results in fewer false positive referrals, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noncontrast magnetic resonance imaging versus ultrasonography for hepatocellular carcinoma surveillance (MIRACLE-HCC): study protocol for a prospective randomized trial. An, C., Kim, DY., Choi, JY., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening. [2023]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

What is the best surveillance for hepatocellular carcinoma in chronic carriers of hepatitis B? [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Diagnostic algorithm for subcentimeter hepatocellular carcinoma using alpha-fetoprotein and imaging features on gadoxetic acid-enhanced MRI. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Abbreviated Liver Magnetic Resonance Imaging Protocols and Applications. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Eliciting Patient Preferences for Hepatocellular Carcinoma Screening: A Choice-Based Conjoint Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Noncontrast magnetic resonance imaging versus ultrasonography for hepatocellular carcinoma surveillance (MIRACLE-HCC): study protocol for a prospective randomized trial. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Abbreviated MRI for hepatocellular carcinoma screening: A systematic review and meta-analysis. [2022]