MRI vs. Ultrasound Screening for Liver Cancer

(PREMIUM Trial)

Recruiting at 17 trial locations

Overseen By Tamar H Taddei, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

4700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods for screening liver cancer in individuals with liver cirrhosis. The researchers aim to determine if a shortened MRI test (Abbreviated Magnetic Resonance Imaging with serum AFP) combined with a blood test is more effective at detecting early liver cancer than the usual ultrasound scan (Abdominal Ultrasound Screening with serum AFP) plus the same blood test. Early cancer detection may lead to more treatment options and better outcomes. Individuals with cirrhosis who are at high risk for liver cancer and have not been diagnosed with or suspected of having liver cancer may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to research that could enhance early detection methods for liver cancer.

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 prior data suggests that these screening methods are safe for liver cancer detection?

Research has shown that using a simpler MRI scan without contrast dye, known as non-contrast abbreviated MRI (aMRI), along with a blood test for alpha-fetoprotein (AFP), effectively detects liver cancer. This method performs as well as traditional screening methods. aMRI is emerging as a promising alternative to ultrasound for liver cancer screening, particularly for high-risk individuals. Studies indicate that the aMRI approach is easy for patients to handle and avoids contrast dye, reducing the risk of side effects often linked to full MRI procedures.

Conversely, an abdominal ultrasound with AFP remains a standard method and is generally well-tolerated, having been widely used without significant safety concerns. Both screening methods aim to detect liver cancer at earlier stages, potentially leading to more effective treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether abbreviated MRI combined with serum AFP can provide more effective liver cancer screening compared to the traditional abdominal ultrasound with serum AFP. Unlike ultrasounds, which are commonly used but sometimes miss small tumors, abbreviated MRI might offer clearer and more detailed images, potentially leading to earlier detection of liver cancer. This trial aims to find out if the advanced imaging capabilities of MRI can improve screening accuracy, helping doctors catch cancer at an earlier, more treatable stage.

What evidence suggests that this trial's screening methods could be effective for early detection of liver cancer?

This trial will compare two screening methods for liver cancer: Abbreviated Magnetic Resonance Imaging with serum AFP (aMRI+AFP) and Abdominal Ultrasound Screening with serum AFP (US+AFP). Research has shown that using a shorter MRI scan (aMRI) with a blood test for a protein marker (AFP) holds promise for early liver cancer detection. Studies have found that aMRI correctly identifies liver cancer 83% of the time and accurately rules it out 91% of the time when absent. This method effectively detects liver cancer and confirms its absence. Compared to traditional ultrasound, aMRI with AFP may reduce liver cancer deaths by 35%. While the AFP test alone isn't always perfect, combining it with aMRI enhances its effectiveness. Overall, this approach shows strong potential for early liver cancer detection, improving the chances of successful treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

George N. Ioannou, MD MS

Principal Investigator

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

Are You a Good Fit for This Trial?

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 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.

My kidney function is low, with a GFR under 30 ml/min.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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

Abbreviated Magnetic Resonance Imaging with serum AFP is already approved in United States for the following indications:

Approved in United States as Abbreviated MRI with AFP for:

• Screening for hepatocellular carcinoma (HCC) in patients with cirrhosis

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

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]

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]

Abbreviated MRI (AMRI) demonstrated high sensitivity (86%) and specificity (94%) for screening hepatocellular carcinoma (HCC) in a systematic review of 15 studies involving 2,807 patients, making it a promising alternative to traditional ultrasound.

While AMRI is effective for detecting larger HCC tumors (≥2 cm), its sensitivity drops for smaller tumors (<2 cm), but it still outperforms ultrasound, which had a sensitivity of only 53%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated MRI for hepatocellular carcinoma screening: A systematic review and meta-analysis. Gupta, P., Soundararajan, R., Patel, A., et al.[2022]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8043710/

Abbreviated Magnetic Resonance Imaging for HCC ... Although the addition of AFP modestly improves sensitivity, it has suboptimal performance for HCC screening and surveillance, being elevated in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10511584/

The combination of non-contrast abbreviated MRI and ... This study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05486572

NCT05486572 | Preventing Liver Cancer Mortality Through ... The study is powered to detect a minimum relative reduction in HCC-related mortality of 35% in the aMRI+AFP arm compared to the US+AFP arm, i.e. a reduction in ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1076633224000515

Abbreviated MRI for Hepatocellular Carcinoma Surveillance The NC-aMRI protocols reported in 21 studies exhibited 83% (79–87%, 63%) sensitivity and 91% (88–93%, 67%) specificity, while the 15 studies on CE-aMRI ...

5. withpower.com withpower.com/trial/phase-cirrhosis-of-the-liver-11-2022-b14aa

MRI vs. Ultrasound Screening for Liver Cancer Research shows that using non-contrast abbreviated MRI (aMRI) with alpha-fetoprotein (AFP) is effective for detecting liver cancer, performing comparably to ...

6. e-jlc.org e-jlc.org/journal/view.php?doi=10.17998/jlc.20.1.25

Liver Magnetic Resonance Imaging for Hepatocellular ... The purpose of this review was to present an overview of the diagnostic performance and cost-effectiveness of liver MRI as an HCC surveillance tool.