HepaT1ca: Quantifying Liver Health in Surgical Candidates for Liver Malignancies

Study Overview
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Brief Summary
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This observational clinical cohort study aims to evaluate the clinical utility of LiverMultiScan in quantifying liver health prior to liver resection or TACE. The results will enable further developments in scanning protocols and software, and clearly define the relevance of applying this technology as part of the pre-operative assessment of the patient being considered for liver resection or TACE.

Detailed Description
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The liver is unique among the abdominal organs for the capacity to regenerate post-operatively. However, a minimum functional liver remnant (FLR) is required for patients to survive the initial perioperative period. At present, the assessment of the FLR is based on volume alone, in the context of clinical judgment and surrogate markers of liver function based on blood tests. Recently, Perspectum Diagnostics have developed and validated LiverMultiScan, an MRI-based technology that can non-invasively quantify fibroinflammatory disease in addition to steatosis and iron content. In this project, we plan to use LiverMultiScan as an additional direct measurement of liver health prior to resectional surgery or transarterial chemoembolization (TACE), so that liver volume and function can be combined. For example, surgery with a predicted FLR of 21% might be survivable if the liver tissue was in extremely good health, whereas surgery with a predicted FLR of 40% might be lethal if the liver tissue was in poor health. Occasionally, portal vein embolization (PVE) is performed to promote hypertrophy of the FLR. Furthermore, non-resectional intervention, for example TACE for primary liver cancers, is well-tolerated by patients with healthy livers, but can lead to serious liver decompensation and liver failure if TACE is delivered to a liver in poor health. Currently, the available imaging modalities are limited in their ability to assess liver health in liver resection or TACE candidates. Liver fat content (steatosis) can be assessed with CT, or more accurately with MRI. However, fibroinflammatory disease, which has been shown to correlate with post-resection morbidity, typically requires an invasive biopsy to diagnose accurately. This research project will support the definition, development and technical validation of Hepatica, which aims to build on the MRI technology underlying LiverMultiScan and develop the additional functionality required to meet this clinical need.

Official Title
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HepaT1ca: Quantifying Liver Health in Surgical Candidates for Liver Malignancies

Conditions
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Liver Cancer, Surgery, Liver Regeneration, Colorectal Cancer Metastatic

Intervention / Treatment
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* Diagnostic Test: Multiparameter magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients being considered for liver resection Exclusion Criteria: i. Patients under the age of 18 years will be excluded from the present study. ii. Prisoners will be excluded from the present study. iii. Persons unable to have an MRI scan (including but not limited to claustrophobia, implanted metallic devices, metal foreign body) iv. Adults with incapacity v. Non-provision of consent

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Nested cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main cohort<br>Patients undergoing liver resection | Diagnostic Test: Multiparameter magnetic resonance imaging<br>* LiverMultiScan before and after surgery to assess liver health prior to liver resection and in the regenerative phase.<br>* Other names: LiverMultiScan;|
| Experimental: Nested cohort PVE<br>Patients undergoing liver resection after portal vein embolisation | Diagnostic Test: Multiparameter magnetic resonance imaging<br>* LiverMultiScan before and after surgery to assess liver health prior to liver resection and in the regenerative phase.<br>* Other names: LiverMultiScan;|
| Experimental: Nested cohort neoadjuvant chemotherapy<br>Patients undergoing liver resection after neoadjuvant chemotherapy | Diagnostic Test: Multiparameter magnetic resonance imaging<br>* LiverMultiScan before and after surgery to assess liver health prior to liver resection and in the regenerative phase.<br>* Other names: LiverMultiScan;|
| Experimental: Nested cohort TACE<br>Patients undergoing trans arterial chemoembolisation for presumed hepatocellular carcinoma | Diagnostic Test: Multiparameter magnetic resonance imaging<br>* LiverMultiScan before and after surgery to assess liver health prior to liver resection and in the regenerative phase.<br>* Other names: LiverMultiScan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the pre-operative liver health assessment score and the post-operative liver function composite integer-based risk score. | Correlation between the pre-operative liver health assessment score (Hepatica score - calculated by weighting future remnant liver volume by liver inflammation and fibrosis (LIF) score) and the post-operative liver function composite integer-based risk (Hyder-Pawlik) score. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare LiverMultiScan image interpretations with histological findings | To compare LiverMultiScan image interpretations with clinical outcome after surgery in three domains: post-operative liver function, surgery-specific complication rate, and overall complication rate | 24 months | 
| • To evaluate LiverMultiScan image interpretations correlated with post-operative length of stay. | • To compare LiverMultiScan image interpretations with histological findings in the resected liver specimen in four domains: fibrosis, inflammation, fat content and iron load as title | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LiverMultiScan, multiparameter MRI, functional liver remnant, liver resection, hepatic resection, portal vein embolisation, preoperative liver function, postoperative liver failure