Trial Information

Evaluation of HCC Response to Systemic Therapy With Quantitative MRI

The incidence of hepatocellular carcinoma (HCC) has recently increased in the US mostly due
to an increase in chronic hepatitis C infection. Angiogenesis is critical for the growth and
metastatic progression of HCC. With the development of new antiangiogenic drugs such as
sorafenib, imaging methods to predict and assess therapeutic response beyond changes in size
become critical. However, validated imaging methods to predict and assess early HCC response
to targeted agents are lacking.

In this study, the investigators would like to develop quantitative MRI methods
interrogating different features of HCC tumor biology and pathology, including tumor
cellularity, grade, angiogenesis and hypoxia. The investigators propose a multiparametric
approach combining advanced DWI (IVIM: intravoxel incoherent motion diffusion measuring
perfusion fraction and true diffusion coefficient), DCE-MRI (dynamic contrast-enhanced MRI,
which measures arterial and portal flow, mean transit time, blood volume and distribution
volume), and BOLD MRI using oxygen or carbogen challenge. This protocol will be performed in
patients with HCC undergoing hepatic resection. Routine and advanced histopathologic methods
will be performed (tumor grade, CK19 expression, presence of microvascular invasion, VEGF
expression, microvessel density, HIF 1-alpha expression). MRI metrics will be correlated
with histopathologic metrics.

The first portion of the proposal involves the development of a QC algorithm assessing MR
data quality and test-retest. The investigators will propose solutions to improve data
acquisition and processing. The last 2 years of the study will be dedicated to a prospective
randomized study comparing Yttrium 90 radioembolization to sorafenib, assessing the role of
baseline MRI metrics and early changes (at 2 weeks) in these metrics as markers of tumor
response and time to progression in patients with unresectable HCC.