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

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.

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