Abbreviated Magnetic Resonance Imaging vs Ultrasound Surveillance for Liver Cancer dETection in People at High Risk of Developing Liver Cancer

Not yet recruiting

• Conditions: Cirrhosis; Cirrhosis Due to Hepatitis B; Cirrhosis Due to Hepatitis C; Cirrhosis and Chronic Liver Disease; Cirrhosis of the Liver; Hepatocellular Carcinoma

• Registration Number: NCT06658782
• Lead Sponsor: University of Oxford

Brief Summary

Aim: To use magnetic resonance imaging (MRI) scans without contrast to help improve diagnosis of liver cancer in people who are at increased risk of developing liver cancer.

Background: People with any condition that affects the liver over a long period of time can develop cirrhosis. Conditions and risk factors that can lead to cirrhosis include alcohol excess, liver steatosis (lipid or fat accumulation in the liver) and infection with the viruses hepatitis B and C. One of the concerns about people with cirrhosis is that they are at increased risk of developing liver cancer. People with cirrhosis are recommended to have an ultrasound scan (USS) every 6 months (surveillance for liver cancer) so that if a cancer develops, it is diagnosed at an early stage when it can be cured. However, ultrasound can miss cancers even in people having scans every 6 months. Furthermore, the risk of cancer is not alike among people with cirrhosis. For example, people with more advanced cirrhosis and those with cirrhosis from hepatitis B are at higher risk. It is therefore possible that better tests than ultrasound are needed for people with cirrhosis who are at particularly high risk of developing cancer.

Computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans with dye injection (contrast) are used for liver cancer diagnosis. However, they cannot be done every 6 months because of costs, capacity and toxicity from high CT radiation doses, and MRI contrast build-up in the brain with repeated MRI contrast injections. MRI scans without contrast are not toxic, could be done in 20 minutes and are cheaper, so could be done every 6 months. In the experience of the study investigators, MRI without contrast may raise suspicion of liver cancer in cases missed by ultrasound, so it could be used for surveillance instead of ultrasound. This study aims to find out if it is feasible to use a quick MRI (20 minutes) without contrast as surveillance for liver cancer in people at high risk of liver cancer due to liver cirrhosis and to compare this MRI with ultrasound.

Design and Methods: The investigators will recruit 300 people at higher risk of developing liver cancer because of cirrhosis. Study participants will have an ultrasound scan every 6 months as they would in their standard clinical care and an additional 6 monthly non-contrast MRI scan for 30 months (6 visits). If the ultrasound or non-contrast MRI raises concern for a possible liver cancer, an MRI scan with contrast (with dye injection) will be done for definitive diagnosis. All participants will have an MRI with contrast at the end of 30 months (M30) to ensure that no cancers were missed. Participants will be asked to complete questionnaires to measure quality of life, anxiety, and their experience of MRI and ultrasound scans and data will be collected from their medical notes. The number of liver cancers detected by ultrasound will be compared to the number detected by the non-contrast MRI scans.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-16
• Study First Submitted QC: 2024-10-23
• Last Update Submitted: 2024-10-23
• Study First Posted: 2024-10-26
• Last Update Posted: 2024-10-26
• Study Start: 2024-12-01
• Primary Completion: 2029-04-30
• Study Completion: 2039-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• • Participant is willing and able to give informed consent for participation in the study AND

  • All genders, aged 18 years or above AND
  • Eligible for HCC US surveillance in the opinion of the local investigators AND
  • Child Pugh score A or B AND
  • Diagnosed with liver cirrhosis due to ArLD, MASLD, chronic hepatitis C, chronic hepatitis B, genetic haemochromatosis AND
  • Have an annual risk of HCC of at least 3% as determined by the aMAP score OR
  • Participants with chronic liver disease (with or without cirrhosis) who had successful treatment for HCC, have not had a recurrence and have returned to 6 monthly surveillance with USS

Exclusion Criteria

• • Contraindication to MRI

  • Known allergy / reaction to intravenous gadolinium contrast
  • Prisoners
  • Pregnancy or breast feeding
  • Previous liver transplant
  • Participants who are known to have indeterminate liver nodules on prior imaging requiring ongoing follow-up with MRI or CT
  • Previous HCC treated with curative intent and still being followed up with CT or MRI with contrast for possible recurrence
  • Estimated glomerular filtration rate of <30 ml/min/1.73m2
  • Participant is on haemodialysis
  • Participants who are unlikely to comply with the study procedures in the opinion of the local investigator
  • In the view of the clinician, if the participant has a co-morbidity likely to lead to death within the following 12 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Diagnostic performance for HCC	from enrolment to 30 months	True positive tests for HCC per round of surveillance False positive tests for HCC per round of surveillance Positive predictive value for HCC per round of surveillance True negative tests for HCC over the 30 months of surveillance False negative tests for HCC over the 30 months of surveillance Sensitivity and specificity of nceMRI and USS for HCC over 30 months of surveillance

Secondary Outcome Measures

Name	Time	Method
mechanistic sub-study quantitative MRI metrics	from baseline to months 30	Quantitative variables extracted from MRI data; T1 (ms), R2\* (ms), PDFF (%), ADC (mm2/s)
stage and size of HCC at diagnosis	from enrolment to 30 months	Numbers of HCC detected by nceMRI and USS at a very early, early, intermediate or advanced stage as defined by the Barcelona Clinic Liver Cancer staging system.; The number and size of HCC tumours per participant with HCC The number of new indeterminate lesions identified at each surveillance round
feasibility	from enrolment to 30 months	Number of missed appointments (cancelled or missed), number of participants lost to follow-up, Number of participants where HCC surveillance is no longer indicated
proportion of participants that receive treatment with curative intent	from enrolment to 30 months	Proportion of participants diagnosed with HCC who go on to receive treatment with curative intent
Quality of Life, Anxiety and Depression	from enrolment to 30 months	Results of the EQ-5D-5L questionnaire and Hospital Anxiety and Depression Scale questionnaire
participant experience	baseline, and month 24	Results of participant experience questionnaire
multivariate models	month 30	Sensitivity and specificity of multivariable models for the diagnosis of HCC
long term outcomes	Up to 10 years after the last study MRI scan is performed	A composite end point including the outcomes of: all cause mortality, liver related mortality, liver decompensation (ascites, hepatic encephalopathy, variceal bleeding), hepatocellular cancer, non primary liver cancer, liver transplantation.