Contrast-Enhanced CT and MRI in Diagnosing and Staging Liver Cancer Using UNOS Policy

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as contrast-enhanced CT scan and contrast-enhanced MRI, may help find liver cancer and find out how far the disease has spread. PURPOSE: This clinical trial is studying contrast-enhanced CT scan and contrast-enhanced MRI in diagnosing and staging liver cancer in patients with chronic liver disease.

Detailed Description
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OBJECTIVES: Primary To compare the sensitivity of multiphase contrast-enhanced CT scan to that of multiphase contrast-enhanced MRI using non-specific contrast agents for diagnosing hepatocellular carcinoma (HCC) in patients with chronic liver disease. Secondary To compare the positive predictive value (PPV) of CT scan to that of MRI for diagnosing HCC. To compare the lesion-level sensitivity and PPV of CT scan and MRI as interpreted by radiologists at the respective transplant centers. To compare the sensitivity and specificity of multiphase contrast-enhanced CT scan vs MRI for diagnosing residual or recurrent HCC after local ablative therapy in patients listed for liver transplant. To determine the accuracy of imaging-based diagnosis and staging of HCC in clinical practice using the new Organ Procurement and Transplantation Network (OPTN) liver-imaging criteria compared with the reference standard of pathologic diagnosis and staging at the time of explantation. To explore whether the comparisons of sensitivity and PPV are affected by stratifying patients by AFP level (elevated vs normal). (Exploratory) Tertiary To assess the sensitivity and PPV of MRI and CT interpreted at the participating sites on the basis of all available information and sequences and compare the sensitivity and PPV of the two modalities interpreted using the main study criterion. (Exploratory) OUTLINE: This is a multicenter study. Patients are stratified according to AFP level (elevated vs normal). Patients undergo CT scan with iodinated contrast agent and MRI with extracellular gadolinium contrast agent (both standard-of-care and study-related) at baseline and at 90-day intervals while on the liver transplant wait list. After transplantation, the explanted liver will be analyzed for biomarkers and other studies.

Official Title
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A Prospective, Multicenter Comparison of Multiphase Contrast-Enhanced CT and Multiphase Contrast-Enhanced MRI for Diagnosis of Hepatocellular Carcinoma and Liver Transplant Allocation

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: iodinated contrast dye
* Drug: motexafin gadolinium
* Other: Eovist-enhanced MRI


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Presence of ≥ 1 focal liver lesion(s) compatible with imaging diagnosis of stage II hepatocellular carcinoma (HCC) (Organ Procurement and Transplantation Network [OPTN] Class 5B liver lesion) on contrast-enhanced CT scan and/or contrast-enhanced MRI OR 2 or 3 focal liver lesions, each between > 1 and < 3 cm diameter, if each is compatible with imaging diagnosis of HCC on contrast-enhanced CT imaging and/or contrast-enhanced MRI Imaging findings must be within the Milan criteria Listed on the regional OPTN/United Network for Organ Sharing (UNOS) liver transplant wait list with HCC-exception MELD points Listed with the intent to undergo either deceased donor transplantation or live donor adult liver transplantation No evidence of any of the following: Extrahepatic tumor Unifocal tumor mass > 5 cm in diameter Multifocal tumors ≥ 4 in number Multiple (≤ 3) HCC with ≥ 1 tumor ≥ 3 cm in diameter PATIENT CHARACTERISTICS: No renal failure, as determined by estimated GFR (eGFR) < 30 mL/min No renal insufficiency, as determined by eGFR 30-60 mL/min Not pregnant Negative pregnancy test Able to comply with breathing and other imaging-related instructions resulting in ability to obtain diagnostic-quality CT scan or MRI studies (OPTN Class 0) None of the following conditions that would make the patient unsuitable to undergo MRI with extracellular gadolinium-based contrast agent that does not have dominant hepatobiliary excretion: Claustrophobia (unless alleviated with sedative treatment) Presence of metallic objects or implanted medical devices in body per institutional safety standards Sickle cell disease Weight greater than that allowable by the MRI table None of the following conditions that would make the patient unsuitable to undergo CT scan with an iodinated contrast agent: Iodinated contrast allergy Weight greater than that allowable by the CT table No known allergy-like reaction to contrast media (iodinated or extracellular gadolinium that does not have dominant hepatobiliary excretion) or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology and unwilling to undergo pre-treatment PRIOR CONCURRENT THERAPY: No local ablative therapy to the liver before study enrollment No prior or concurrent sorafenib (or comparable antiangiogenic therapy) Patients planning to undergo local ablative therapy after transplant listing and study enrollment are eligible provided they undergo CT scan and MRI within 28-60 days after completing the last ablative therapy session Patients planning to receive transcatheter arterial chemoembolization (TACE) or combination therapy with TACE and thermal ablation are eligible provided they complete the entire treatment scheme per institutional standard of care before undergoing CT scan and MRI

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Waitlisted with HCC-Exception Points<br>Participants undergo CT and MRI every 90 days for the trial with iodinated contrast dye and motexafin gadolinium, during liver transplant wait listing. Possible Eovist-enhanced MRI substudy participation | Drug: iodinated contrast dye<br>* iodinated Radiocontrast dye for imaging enhancement<br>* Other names: iodinated radiographic dye;Drug: motexafin gadolinium<br>* motexafin gadolinium<br>* Other names: Xcytrin;Other: Eovist-enhanced MRI<br>* A sub-study introduces the Eovist contrast agent for MRI scans at the same time points as the parent policy-assessment trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of contrast-enhanced CT scan vs contrast-enhanced MRI for diagnosing hepatocellular carcinoma (HCC) |  | Within 90 Days Before Transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive predictive value (PPV) of CT scan vs MRI for diagnosing HCC |  | Within 90 Days Before Transplantation | 
| Lesion-level sensitivity and PPV of contrast CT scan vs contrast MRI |  | Within 90 Days Before Transplantation | 
| Sensitivity and specificity of multiphase contrast-enhanced CT scan vs MRI for diagnosing residual or recurrent HCC |  | Within 90 Days Before Transplantation | 
| Accuracy of imaging-based diagnosis and staging of HCC in clinical practice using the new OPTN liver-imaging criteria compared with the reference standard of pathologic diagnosis and staging at the time of explantation |  | Within 90 Days Before Transplantation | 
| Diagnostic value of sensitivity and PPV when patients are stratified by AFP level (elevated vs normal) |  | Within 90 Days Before Transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer