PET/CT in Diagnosing Patients With Liver Cancer Undergoing Surgical Resection

Study Overview
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Brief Summary
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This clinical trial studies positron emission tomography (PET)/computed tomography (CT) in diagnosing patients with liver cancer undergoing surgical resection. Diagnostic procedures, such as fluorine-18 fluoromethylcholine PET/CT, may help find and diagnose liver cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the most optimal fluorine-18 (18F) fluoromethylcholine (FCH) PET/CT parameters for detecting primary hepatocellular carcinoma (HCC) by conducting a clinical radiologic-pathologic correlation study to estimate and compare the receiver operating characteristics of kinetic and static PET measures of tumor FCH metabolism in patients that test positive during screening or conventional imaging. II. Identify cancer signaling pathways associated with choline metabolism in HCC by profiling the global gene expression patterns in fresh-frozen liver tissue samples that are correlated with the features derived from FCH PET/CT images. III. Characterize the association between features derived from FCH PET/CT images of the liver and clinical liver disease severity and comparatively evaluate the ability of corresponding gene expression signatures to predictively model HCC disease outcome. OUTLINE: Patients undergo 18F-fluoromethylcholine PET/CT within 14 days of surgical resection. After completion of study treatment, patients are followed up periodically.

Official Title
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Genomic and Imaging Study for Patients Undergoing Surgery for Liver Cancer

Conditions
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Adult Hepatocellular Carcinoma, Localized Resectable Adult Liver Carcinoma

Intervention / Treatment
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* Diagnostic Test: Computed Tomography
* Drug: 18F-fluoromethylcholine
* Diagnostic Test: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver tumor diagnosed histologically as HCC or suspected of being HCC in association with serum alpha-fetoprotein level > 200 or tumor mass with characteristics of malignancy on diagnostic imaging Under the care of a surgical attending Deemed a surgical candidate and has agreed to surgery to remove a portion of the liver containing tumor Child-Pugh A/B Exclusion Criteria: Weight > 350 lbs Pregnant or lactating female, a serum pregnancy test will be performed within 2 weeks or less before the date of the FCH PET/CT scan in all women capable of becoming pregnant Serious underlying medical condition that would impair patient's ability to tolerate the imaging procedure Concurrent treatment with chemotherapy, molecule-selective, biological, or radiotherapeutic agent

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-fluoromethylcholine PET/CT<br>Patients undergo 18F-fluoromethylcholine positron emission tomography (PET)/ computed tomography (CT) scan within 14 days of surgical resection of liver tumor. | Diagnostic Test: Computed Tomography<br>* Undergo FCH PET/CT<br>* Other names: tomography;Drug: 18F-fluoromethylcholine<br>* Undergo FCH PET/CT<br>* Other names: FCH;Diagnostic Test: Positron Emission Tomography<br>* Undergo FCH PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve. | Area under the receiver operating characteristic curve for detecting resectable hepatocellular carcinoma with prognostically favorable molecular features (Hoshida molecular sub-class S3) based on FCH PET/CT measurement of tumor maximum standardized uptake value (SUVmax). | Up to study completion at an average of 2.5 years | 
| Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity | Sensitivity and specificity estimated at a predefined point (ie. Youden's maxima) on the receiver operating characteristic curve for detecting hepatocellular carcinoma with prognostically favorable molecular features (Hoshida molecular sub-class S3) based on FCH PET/CT measurement of tumor maximum standardized uptake value (SUVmax) in patients who underwent subsequent tumor resection. | Up to study completion at an average of 2.5 years | 
| Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | Statistically significant enrichment by sets of genes corresponding to previously-defined molecular pathway signatures was assessed by gene set enrichment analysis (a publicly available algorithm) of whole-genome expression array data obtained from tumors previously characterized by FCH PET/CT. Statistical significance was based on a false discovery rate < 0.05. Tumors demonstrating high choline metabolism (defined by a tumor-liver ratio > 1.0 measured on PET) were assessed for enrichment by publicly-available gene sets. This particular analysis involved the entire Molecular Hallmarks gene signature collection (v6.0) as obtained from the Broad Institute Molecular Signature Database (MSigDB). | Up to study completion at an average of 2.5 years | 
| Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Odds ratios and 95% confidence intervals for histologic liver fibrosis (Metavir) stage >= F1, >= F2, >= F3, and F4 at liver standardized uptake value (SUV) thresholds of 8.3, 8.0, 7.4, and 6.4, respectively. Reference: PMID 29315063. | Up to 1 year | 
| Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC tumors were sub-classified using gene expression arrays into 3 distinct prognostically-relevant molecular sub-classes (S1,S2, S3, where S3 is associated with the most favorable clinical prognosis) based on Hoshida et. al (PMID 19723656). The number of tumors comprising two distinct PET/CT imaging phenotypes (high FCH uptake vs. low FCH uptake) was compared between the different sub-classes. | Up to study completion at an average of 2.5 years |