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NCT Number: NCT01871545

Evaluation of Liver Cancer With Magnetic Resonance Imaging (MRI)

The incidence of hepatocellular carcinoma (HCC) has recently increased in the United States. Although imaging plays a major role in HCC screening and staging, the possibility of predicting HCC tumor grade, aggressiveness, angiogenesis and hypoxia with imaging are unmet needs. In addition, new antiangiogenic drugs now available to treat advanced HCC necessitate the use of new imaging criteria beyond size. The investigators would like to develop and validate non-invasive magnetic resonance imaging (MRI) methods based on advanced diffusion-weighted imaging (DWI), MR Elastography, BOLD (blood oxygen level dependent) MRI and perfusion-weighted imaging (PWI, using gadolinium contrast) to be used as non-invasive markers of major histopathologic features of HCC, and to predict and assess early response of HCC to systemic therapy. The investigators also would like to develop quality control tools to improve the quality and decrease variability of quantitative MRI metrics. These techniques combined could represent non-invasive correlates of histologic findings in HCC, could enable individualized therapy, and provide prognosis in patients with HCC.

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms HCC Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Icahn School of Medicine at Mount Sinai

New York, 11103, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Study group

  • Patients diagnosed with HCC, who will undergo resection or transplantation within 6 months, as part of routine clinical care and patients diagnosed with unresectable HCC
  • 18 years of age and older
  • Patient is able to give informed consent for this study

Control group

  • Healthy volunteers 18 years of age and older
  • Subject is able to give informed consent for this study

Exclusion criteria

  • Age less than 18 years
  • Unable or unwilling to give informed consent
  • Contra-indications to MRI:
  • Electrical implants such as cardiac pacemakers or perfusion pumps
  • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
  • Ferromagnetic objects such as jewelry or metal clips in clothing
  • Pregnant subjects
  • Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions

Treatment and study plan

Magnetic Resonance Imaging

Device

Magnetic Resonance Imaging is a radiation free non invasive technique using magnetic radiofrequency waves to image the body. In this study, the research team would like to investigate the possibility of providing functional information on aggressiveness, vascularity and oxygen uptake in liver cancer tumors.

Other names: MRI

Primary outcomes

  1. SubStudy 1: Apparent Diffusion Coefficient (ADC)

    Time frame: Day 1

    Tumor diffusion (apparent diffusion coefficient) measured with diffusion-weighted imaging sequence

  2. SubStudy 1: Total Tumor Perfusion (Ft)

    Time frame: Day 1

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  3. SubStudy 1: Tumor Arterial Perfusion Fraction (ART)

    Time frame: Day 1

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  4. SubStudy 1: Tumor Mean Transit Time (MTT)

    Time frame: Day 1

    Tumor mean transit time (MTT) of contrast agent. Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  5. SubStudy 1: Tumor Distribution Volume (DV)

    Time frame: Day 1

    Tumor distribution volume (DV) of contrast agent. Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  6. SubStudy 1: Oxygen Uptake

    Time frame: Day 1

    Oxygen uptake measured with T2* and T1-weighted imaging

  7. SubStudy 1: Percent Change in Oxygen Uptake

    Time frame: Day 1, pre-oxygen administration and 10 min. post-oxygen administration

    Oxygen uptake measured with T2* and T1-weighted imaging. Oxygen uptake (% change pre and post O2 administration) calculated by Liver ΔR2*=100 x (R2* post O2-R2* pre O2)/R2* pre O2. The healthy participants breathed 100% medical O2 through a mask for 10 min., and were imaged before and after O2 administration with the MRI methods that are sensitive to oxygen uptake in tumors.

  8. SubStudy 2: ADC

    Time frame: baseline and 6 weeks after Y90

    Tumor diffusion measured with diffusion-weighted imaging sequence. In diffusion weighted MR imaging (DWI), the signal is proportional to the Brownian motion diffusion of free water protons in tissues. Deposition of collagen in tissue (as in fibrotic disease), or cellularity in tumors act as impediments to free water diffusion. Using different mathematical models, the degree of diffusion can be quantified from the MRI signal, to provide information on diffusion restriction due to disease. From mono exponential fit of diffusion signal, one can obtain the apparent diffusion coefficient (ADC). However, this coefficient reflects free water proton diffusion, as well as transport of water protons in the capillary vessels (capillary perfusion).

  9. SubStudy 2: Diffusion Coefficient D

    Time frame: baseline and 6 weeks after Y90

    Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the true diffusion coefficient D, reflecting free water proton diffusion.

  10. SubStudy 2: Pseudodiffusion Coefficient D*

    Time frame: baseline and 6 weeks after Y90

    Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the pseudo-diffusion coefficient D*, affected by free diffusion and capillary perfusion.

  11. SubStudy 2: Perfusion Fraction (PF)

    Time frame: baseline and 6 weeks after Y90

    Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the perfusion fraction PF, which reflects how much the diffusion-weighted signal is affected by capillary perfusion. PF is a measure of vascularity in the tissue.

Secondary outcomes

  1. SubStudy 2: Total Tumor Perfusion (Ft)

    Time frame: baseline and 6 weeks after Y90

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  2. SubStudy 2: Tumor Arterial Perfusion Fraction (ART)

    Time frame: baseline and 6 weeks after Y90

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  3. SubStudy 2: Tumor Mean Transit Time (MTT) of Contrast Agent

    Time frame: baseline and 6 weeks after Y90

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast

  4. SubStudy 2: Extravascular Extracellular Volume ve

    Time frame: baseline and 6 weeks after Y90

    Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast. Extravascular extracellular volume fraction ve (%) - represents the portion of tissue occupied by the extravascular extracellular volume (interstitial space), in which MRI contrast agent can distribute.

  5. Substudy 2: Tumor Stiffness

    Time frame: baseline and 6 weeks after Y90

    measured with magnetic resonance elastography

  6. Tumor Response

    Time frame: 6 weeks and 6-12 months

    Tumor response to treatment is evaluated clinically by radiologists according to RECIST and modified RECIST criteria, by which the diameter of the tumor portion that enhances (lights up on imaging) after administration of gadolinium contrast agent is measured before and after treatment. The response is not reported as diameter or diameter difference in mm, but rather as a qualitative variable: complete response, partial response, stable disease and progressive disease. Complete response means no enhancing tumor regions after treatment (i.e. complete tumor necrosis, no more vascular regions of the tumor that take up contrast), partial response is a decrease in the diameter of the enhancing region, stable disease is unchanged diameter, and progressive disease is an increase in the diameter of the enhancing region after treatment.

Sponsors and collaborators

Lead sponsor

Icahn School of Medicine at Mount Sinai

Other

Registry information

Official study title

Evaluation of HCC Response to Systemic Therapy With Quantitative MRI

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
Jun 6, 2013
Registry last updated
Jul 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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