Clinical trial NCT01446666: Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients
Official title: A Prospective Intra-individual Cohort Study to Compare Gadoxetic Acid (Primovist®)-Enhanced Magnetic Resonance Image and Ultrasonography for the Surveillance of Early Stage Hepatocellular Carcinoma in Patients at High-risk
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cirrhosis of Liver
Keywords: hepatocellular carcinoma
surveillance
gadoxetic acid
MRI
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2011-10-05
Enrollment: 423
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospital out-patient clinic

Brief summary: Current practice guidelines recommend surveillance for hepatocellular carcinoma (HCC) in liver cirrhosis patients with ultrasonography (USG) every 6 months. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases. Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) has been demonstrated to be of clinical value for diagnosis of HCC with the detection sensitivity of 90-95%, which is significantly higher than USG. The hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC.

Detailed description: Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related deaths worldwide. Cirrhosis, particularly when related to viral hepatitis, is the most notable risk factor for HCC and is found in nearly 80-90% of cases.

The stage of disease at the time of diagnosis largely determines the effectiveness of treatment. The treatment of advanced HCC continues to be primarily palliative, with curative options only available for early HCC. Unfortunately, less than 30% of patients are diagnosed early enough to meet criteria for resection, transplantation, or local ablation.

Surveillance strives to detect HCC at an early stage when it is amenable to curative therapy to reduce mortality. Current practice guidelines recommend surveillance of cirrhotic patients with ultrasonography (USG) every 6 months. However, USG has been reported to have a sensitivity of between 65% and 80% when used as a screening test. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases.

Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) of the liver has been demonstrated to be of clinical value for local staging before HCC surgery and for the assessment of patients with inconclusive conventional imaging findings. The detection sensitivity of Primovist-MRI has been known to be as high as 90-95%, which is significantly higher than USG or multiphase computer tomography (CT) scan. MRI does not have radiation exposure, which is a meaningful merit to be used as a surveillance test. However, MRI has never been considered for surveillance or screening of HCC.

Thus, the hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC. The investigators will also analyze whether the specificity of Primovist-MRI are not compromised by its high sensitivity.

Eligibility criteria: Inclusion Criteria:

Patients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of following criteria;

1. The evidence of cirrhosis of any etiology within 12 months prior to screening Definition of cirrhosis by any of following methods

   * 1) Histologically by liver biopsy;
   * 2) Non-histologically by evidence of portal hypertension in the presence of chronic liver disease;

     * Evidence of portal hypertension, including any of followings;

       1. The identification of splenomegaly on USG, CT, or MRI examinations with typical features of cirrhosis
       2. The identification of esophageal or gastric varices on endoscopic examination
2. High Risk Index (\>=2.33); Risk Index = 1.65 (if the prothrombin activity is \<=75%) + 1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is \<=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus \[HCV\] or hepatitis B surface antigen \[HBsAg\] is positive).
3. Older than 20 years of age
4. Absence of previous or current history of HCC
5. Absence of HCC should be identified by liver USG, dynamic CT, or contrast-enhanced MRI within 6 months prior to screening
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
7. Patient is able to comply with scheduled visits, evaluation plans, and other study procedures.
8. Patient is willing to provide written informed consent

Exclusion Criteria:

Presence of any of following criteria;

1. Active or suspected cancer other than HCC, or a history of malignancy where the risk of recurrence is \>20% within 2 years
2. Child-Pugh score \>9
3. Significant medical comorbidities in which survival is predicted to be less than 3 years
4. Estimated glomerular filtration rate (GFR) \< 30 mL/min/1.73m2
5. Precautions for MRI (cardiac pacemaker, ferromagnetic implants, etc.)
6. Severe claustrophobia that may interfere with protocol compliance.
7. Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the completing the study.

Primary outcomes:
measure: Detection Rate of Patients With HCC
timeFrame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Secondary outcomes:
measure: Detection Rate of Patients With Early Stage HCC
timeFrame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
measure: Detection Rate of Patients With Very Early Stage HCC
timeFrame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
measure: False Positive Rate
timeFrame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
measure: Positive Predictive Value for HCC
timeFrame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Young-Suk Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK. Magnetic Resonance Imaging Is Cost-Effective for Hepatocellular Carcinoma Surveillance in High-Risk Patients With Cirrhosis. Hepatology. 2019 Apr;69(4):1599-1613. doi: 10.1002/hep.30330. Epub 2019 Feb 25.
citation: Kim SY, An J, Lim YS, Han S, Lee JY, Byun JH, Won HJ, Lee SJ, Lee HC, Lee YS. MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma. JAMA Oncol. 2017 Apr 1;3(4):456-463. doi: 10.1001/jamaoncol.2016.3147.