Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03839706 |
| Other study ID # |
17-6065 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 22, 2018 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
December 2023 |
| Source |
University Health Network, Toronto |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Liver transplantation is the standard treatment for patients with early-stage Hepatocellular
Carcinoma (HCC). Currently, important treatment decisions, like the selection of patients for
transplantation, are made on crude, static tumour characteristics such as the size and number
of lesions that do not reflect other aspects of tumour biology. To date, pre-transplantation
percutaneous biopsy is the best strategy to assess tumoral differentiation and, consequently,
tumor biological behavior. Previous studies have demonstrated that 18F-Fluorodeoxyglucose
Positron Emission Tomography Magnetic Resonance Imaging (18F-FDG PET/MRI) may have role in
assessing the HCC tumoral differentiation and predict survival after LT. The Investigators
will assess the accuracy of 18F-FDG PET/MRI as a tool to predict HCC recurrence after liver
transplant. To understand the role of 18F-FDG PET/MRI in prediction of HCC's biological
behavior and upon recurrence, the investigators will try to assess whether the findings in
18F-FDG PET/MRI can predict HCC poor tumoral differentiation, if the findings in 18F-FDG
PET/MRI are related to presence of circulating tumoral DNA in plasma and try to determine the
role of 18F-FDG PET/MRI in predicting HCC recurrence after resection. These findings may
impact the selection criteria for liver transplantation.
Description:
Hepatocellular Carcinoma (HCC) is the third leading cause of death by cancer worldwide, being
responsible for nearly 700,000 deaths in 2012. Liver transplantation (LT) provides the best
results as a curative treatment for patients with early-stage HCC. Other curative treatment
strategies for early stages HCC include resection and ablation. However, the recurrence rates
are higher than LT. Due to organ shortage, better criteria for recipient selection are
necessary. The first widely accepted criteria for graft allocation in HCC patients is the
so-called Milan Criteria (MC): single HCC nodule ≤ 5 cm or 3 nodules all ≤ 3 cm, achieving a
4-y survival of 85%. Recently, MC is seen as too restrictive, its inclusion preventing
patients who might have better survival following LT when compared to other therapies.
Reluctant to have sizing-only criteria, the University of Toronto, since 2004, has applied
the so-called Extended Toronto Criteria (ETC) to LT, which offers transplant to patients with
any size and any number of tumors provide they do not have systemic cancer-related symptoms,
extrahepatic disease, vascular invasion or poorly differentiated tumors. A recent prospective
study conducted at University Health Network (UHN) has shown 5-years survival rates of 68%
when ECT are applied. Recent studies have demonstrated the need to use, besides the lesion
size, variables which can predict the biological behavior of the tumor.
Currently, important treatment decisions, like the selection of patients for transplantation,
are made on crude, static tumour characteristics such as the size and number of lesions, but
do not reflect other aspects of tumour biology. To date, pre-transplantation percutaneous
biopsy is the best strategy to assess tumor differentiation and, consequently, tumor
biological behavior. However, HCC is a very complex disease. Microscopic and molecular
analyses have demonstrated a highly heterogeneous degree of cell differentiation. Patients
with more than one tumor may have two or three degrees of cell differentiation between the
tumors. Even within a single HCC nodule, more than one clonal mutations can be present. To
date, there is not a precise method to determinate the degree of differentiation of each
patient's disease and percutaneous core biopsy, an invasive method, is the best estimative
the investigators can reach.
Since it is impossible to precisely determine the degree of differentiation of HCC with one
single tissue sample, the use of imaging becomes necessary. Magnetic resonance imaging (MRI)
and enhanced computed tomography (CT) are extensively validated as staging methods for HCC.
The use of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Magnetic Resonance
Imaging (PET/MRI) is still underevaluated in the field of HCC. However, previous studies have
demonstrated that 18F-FDG PET/CT may have role in assessing the HCC tumoral differentiation
and predict survival after LT. There is no investigation on use of 18F-FDG PET/MRI as a tool
to predict biological behavior in HCC.
Recently, the Pugh Lab has developed a circulating tumor DNA (ctDNA) sequencing assay that
combines a hybrid-capture method with a novel bioinformatics algorithm to enable full-length
sequence analysis of all exons in genes of interest or any other arbitrary genomic region,
rather than mutation hotspots13. With the availability of these technologies in our group,
the investigators next sought to determine whether these methods were applicable to HCC
patients, gathering two innovative tools in transplant patients' care.
