Hepatectomy Risk Assessment With Functional Magnetic Resonance Imaging

NCT04705194 | Unknown

• 3 other identifiers: RL19/41424MR/P023398/119/NW/0139
• Study Type: observational
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

Liver resection remains the only curative option for primary or metastatic liver cancer, but a more accurate prediction of post-hepatectomy liver failure (PHLF) is needed to further reduce morbidity and mortality and to extend the indication to a wider patient population. Magnetic resonance Imaging (MRI) is a promising new source of liver function tests as it can provide segmental function alongside measurements of perfusion, tissue structure and standard morphological assessment. The primary aim of HEPARIM is to determine if quantitative MRI biomarkers of liver function and perfusion can improve predictions of post-hepatectomy liver function, as measured by an indocyanine green (ICG) liver function test. Secondary aims is to validate the MRI measurements of liver function against ICG. HEPARIM is an observational cohort study recruiting patients referred locally for a one- or two-stage liver resection of 2 segments or more. Before surgery, all participants will undergo an ICG liver function test and a Dynamic Gadoxetate-enhanced (DGE) MRI scan of the liver. The ICG test will be repeated at one day after surgery. The Gadoxetate Clearance (GC) of the future liver remnant (FLR-GC) will be determined from the DGE-MRI data and correlated to the post-operative ICG R15 as primary outcome measure. Preoperative ICG R15 will be correlated against GC of the whole liver (WL-GC) to address the secondary objective. In patients that undergo a staged hepatectomy, an additional MRI and ICG test will be performed before the first stage to assess its effect on volumetric and functional growth of the FLR. Additional pre- and postoperative data will be collected from medical records including demographics and medical histories, biochemistry, pathology and radiology reports, and any long-term outcome data collected in the 90-day follow-up visit. These data will be used in a multi-variate analysis to determine which preoperative biomarkers are most predictive of immediate and long-term outcomes, to identify the added value of functional MRI over routine clinical markers, and to derive a multi-variate prediction model that can be validated in future studies.

Conditions

Hepatectomy; Liver Failure; Liver Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Correlation coefficient between preoperative FLR-GC and post-operative ICG R15

  Correlation between preoperative estimates of liver function using gadoxetate clearance of the FLR (FLR-GC) derived from MRI data and post-operative measurement of liver function using ICG clearance

  End of 2 year recruitment

Secondary Outcomes (2)

• Correlation coefficient between preoperative WL-GC and pre-operative ICG R15

  End of 2 year recruitment

• Correlation coefficient between growth in FLR volume and growth in FLR-GC after the first stage

  End of 2 year recruitment

Study Arms (2)

One stage resection

Patients that are selected for a single hepatectomy of 2 segments or more.

Procedure: Hepatectomy

Two stage resection

Patients that are selected for a two-stage resection, where the first stage consists of either PVE or ALPPS and the second stage is a hepatectomy of 2 or more segments.

Procedure: Hepatectomy; Procedure: PVE or ALPPS

Interventions

Hepatectomy PROCEDURE

Resection of one or more liver segments as treatment for primary or metastatic liver cancer

Also known as: Liver resection

One stage resection; Two stage resection

PVE or ALPPS PROCEDURE

Embolization of the portal vein feeding the diseased liver segments or surgical liver partition and portal vein ligation of the diseased liver segments in order to induce growth of the future liver remnant ahead of the resection.

Two stage resection

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients referred for liver resection of two segments or more as treatment for any metastatic or primary liver cancer.

You may qualify if:

• Adults over 18 years of age and under 80 years
• Referred to the hepatobiliary surgical service at St James's Hospital
• Diagnosed with any hepatic tumour
• One of:
• i) Referred for liver resection (defined as two or more Couinaud segments) by multi-disciplinary team discussion at Saint James's Hospital (One stage arm) ii) OR Referred for PVE or ALPPS prior to likely major hepatectomy by multi-disciplinary team discussion at Saint James's Hospital (Two stage arm)

You may not qualify if:

• Unable to consent independently
• Previous liver resection
• Private patients
• Concurrent malignancy unrelated to liver tumour
• Chronic renal failure (estimated Glomerular Filtration Rate \< 30 mL/min)
• Possible pregnancy
• Other contraindications to DGE-MRI, including:
• i) Cochlear Implant ii) Aneurysm Clips iii) Neurological stimulator iv) Implanted cardiac devices v) Metal heart valve vi) History of metal foreign bodies in orbits vii) Other implanted metal device which prevents MRI viii) Known allergy to Gadolinium contrast ix) Claustrophobia x) Weight exceeding 250 kg xi) Maximal diameter exceeding 55cm
• Other contraindications to ICG i) Known allergy to Indocyanine green ii) Known allergy to sodium iodine iii) Known reaction or allergy to iodine iv) Previous diagnosis of a thyroid problem v) Breastfeeding

Sponsors & Collaborators

• University of Leeds: lead
• The Leeds Teaching Hospitals NHS Trust: collaborator
• University of Sheffield: collaborator

Study Sites (1)

The Leeds Teaching Hospital Trust

Leeds, United Kingdom

RECRUITING

Related Publications (1)

• Elsharif M, Roche M, Wilson D, Basak S, Rowe I, Vijayanand D, Feltbower R, Treanor D, Roberts L, Guthrie A, Prasad R, Gilthorpe MS, Attia M, Sourbron S. Hepatectomy risk assessment with functional magnetic resonance imaging (HEPARIM). BMC Cancer. 2021 Oct 23;21(1):1139. doi: 10.1186/s12885-021-08830-4.

  PMID: 34688256 DERIVED

Related Links

• Project description on the website of the funder

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Liver Failure; Liver Neoplasms

Interventions

Hepatectomy

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Digestive System Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Steven Sourbron, PhD

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven Sourbron, PhD

CONTACT

+44 114 215 9155; s.sourbron@sheffield.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 12, 2021
• Study Start: July 8, 2019
• Primary Completion: March 1, 2022
• Study Completion: June 1, 2022
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After publication of the primary and secondary outcomes (expected end 2022)
• Access Criteria: The excel table with anonymised research data will be made freely available as supplementary material with the publications. A small number of MRI data will be freely accessible as examples. Access to the entire dataset of MR images and raw k-space data will be conditional and subject to submission of a study plan and approval by the study PI.

Locations

GB (1)