The Detection of Small Early Liver Cancer With Natural History Follow up

Study Overview
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Brief Summary
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The SELINA study will recruit 200 patients with cirrhosis and small HCC and 50 patients with HCC but without cirrhosis (most of whom are expected to have FLD). Blood, urine and liver tissue samples (where available) will be collected for laboratory analysis. In a subgroup of patients (N=80, around 64 patients with HCC with liver cirrhosis and around 16 patients with HCC without liver cirrhosis), additional magnetic resonance liver imaging will be performed. The findings of the SELINA study aim to identify biomarkers that can be used to detect liver cancer at the earliest possible time, something we expect will increase the survival rate of HCC.

Official Title
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The Detection of Small Early Liver Cancer With Natural History Follow up

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Other: Blood & Urine Samples
* Other: Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study. Male or Female aged 18 years or above. Diagnosed with small HCC (Barcelona Clinic Liver Cancer Staging Criteria (BCLC) stage 0/A; 1-3 nodules <3cm, preserved liver function, performance status 0) with liver cirrhosis from any aetiology Diagnosed with small HCC (as above) and without cirrhosis Diagnosis of small HCC shown or confirmed within 3 months of study Visit 1 Patients with a diagnosis of HCC that was fully ablated or resected more than 6 months ago and now presenting with a new diagnosis of HCC in a different site in the liver may be included in the study Histological confirmation is required to establish the diagnosis of HCC in patients without cirrhosis (imaging alone is not considered sufficient to establish the diagnosis of HCC). Exclusion Criteria: Patients judged by the investigator to be unsuitable for inclusion in the study (e.g. where the investigator feels that the participant will not be able to comply with the study procedures) HCC with liver cirrhosis at BCLC stage B/C Patients who have had a previous liver transplant (note, it is permitted to enrol patients on the liver transplant waiting list if they fulfil all inclusion/exclusion criteria) Participants of the Pearl study Patients who have had a previous diagnosis of HCC followed by therapy, and now have a recurrence at the same site in the liver Patients who have received HCC specific therapy 3 months prior to study visit 1 (including resection, ablation [microwave/radiofrequency]), transarterial chemoembolization [TACE], select internal radiation therapy [SIRT] or stereotactic body radiation therapy [SBRT] 3, chemotherapy, immune modulators and other experimental therapies). Exclusion Criteria for Imaging Subgroup 1. Any contra-indication to Magnetic Resonance Imaging (MRI) (e.g. claustrophobia, metal implants/fragments, implants, pregnancy, other conditions the scanner operator deems unsafe for MR scanning).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Small HCC with Cirrhosis<br>200 patients diagnosed with small HCC (as defined in Eligibility Criteria) and cirrhosis | Other: Blood & Urine Samples<br>* Blood and urine samples will be collected to help identify biomarkers that can be used to detect liver cancer at the earliest possible time<br>|
| Small HCC without Cirrhosis<br>50 patients diagnosed with small HCC (as defined in Eligibility Criteria) but without cirrhosis | Other: Blood & Urine Samples<br>* Blood and urine samples will be collected to help identify biomarkers that can be used to detect liver cancer at the earliest possible time<br>|
| Imaging Subgroup<br>In a subgroup of patients (N=80, around 64 patients with HCC with liver cirrhosis and around 16 patients with HCC without liver cirrhosis), additional magnetic resonance liver imaging & elastography will be performed | Other: Imaging<br>* MRI & MRE Scans<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers associated with small HCC (Early detection [EDx] biomarkers) | Classification performance metrics of EDx biomarkers, in cirrhosis patients with small HCC compared to non-HCC cirrhosis patients | Throughout study to completion; up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic ability of Early Detection (EDx) bio-markers | Ability of EDx biomarkers to discriminate between individuals who go onto develop adverse outcomes (e.g. HCC rapid tumour progression, liver decompensation, liver related mortality, liver transplantation) versus those who do not. Measured via Harrell's concordance index and Royston's D statistic. | Throughout study to completion; up to 5 years | 
| Whether combinations of EDx tests improve the diagnostic and prognostic performance | Model fit statistics comparing univariate and multivariate models, including Harrell's adequacy index. The change in model discrimination (e.g. Delta Concordance-index and Delta D-statistic) will also be considered. | Throughout study to completion; up to 5 years | 
| Proportion of patients with HCC events according to time since treatment with curative intent. | To study the natural history of small HCC. Proportion of patients with HCC recurrence, all-cause mortality, liver mortality etc, according to time since treatment with curative intent.. | Throughout study to completion; up to 5 years |