Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Hematinics

Nootropic Agents

Gastrointestinal Agents

Lipid Regulating Agents

Vitamins

Fluorides

Liver Extracts

Choline

Hypolipidemic Agents

Antimetabolites

Patients undergo 18F-fluoromethylcholine positron emission tomography (PET)/ computed tomography (CT) scan within 14 days of surgical resection of liver tumor.

Computed Tomography

18F-fluoromethylcholine

Positron Emission Tomography

Sandi Kwee, MD

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.

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.

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

Genomic and Imaging Study for Patients Undergoing Surgery for Liver Cancer

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).

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.

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).

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.

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.

National Cancer Institute (NCI)

Queen's Medical Center

Principal Investigator

Patients undergo 18F-fluoromethylcholine PET/CT scan within 14 days of surgical resection.

Computed Tomography: Undergo FCH PET/CT

18F-fluoromethylcholine: Undergo FCH PET/CT

Laboratory Biomarker Analysis: Correlative studies

Positron Emission Tomography: Undergo FCH PET/CT

18F-fluoromethylcholine PET/CT

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Tumor Diagnosis

Program Director for PET Research

All primary liver cancers (n=50)

HCC only (n=41)

Patients undergo fluorine-18 (18F-) fluoromethylcholine (FCH) positron emission tomography (PET)/ computed tomography (CT) scan within 14 days of surgical resection.

Computed Tomography: Undergo FCH PET/CT

18F-fluoromethylcholine: Undergo FCH PET/CT

Laboratory Biomarker Analysis: Correlative studies

Positron Emission Tomography: Undergo FCH PET/CT

Patients from whom surgical tumor resection (ie. partial hepatectomy) provided adequate tumor and liver samples for tissue analysis.

Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve.

Sensitivity for HCC sub-class S3

Specificity for HCC sub-class S3

Patients undergo 18F-fluoromethylcholine positron emission tomography (PET)/ computed tomography (CT) scan within 14 days of surgical resection of liver tumor.

Computed Tomography: Undergo FCH PET/CT

18F-fluoromethylcholine: Undergo FCH PET/CT

Positron Emission Tomography: Undergo FCH PET/CT

Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity

Analysis was performed using Gene Set Enrichment Analysis (GSEA version 19.0.24, Broad Institute, Cambridge, MA) implemented in GenePattern (Broad Institute, Cambridge, MA) by uploading expression array data to this cloud-computing genomics platform. The specific details of this statistical approach can be found in the following publicly available references:

Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP. GenePattern 2.0 Nature Genetics 38 no. 5 (2006): pp500-501

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. PNAS. 2005;102(43);15545-15550.

HALLMARK_OXIDATIVE_PHOSPHORYLATION

HALLMARK_ADIPOGENESIS

HALLMARK_PEROXISOME

HALLMARK_XENOBIOTIC_METABOLISM

HALLMARK_FATTY_ACID_METABOLISM

HALLMARK_BILE_ACID_METABOLISM

Patients with histopathologically confirmed HCC who completed FCH PET/CT followed by completion of whole-genome expression array analysis of tumor and adjacent liver tissue obtained following partial hepatectomy.

Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples.

Fibrosis stage >= F1

Fibrosis stage >= F2

Fibrosis stage >= F3

Fibrosis stage F4

Number of subjects with available peri-tumoral liver histopathology data

Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage

HCC sub-class S1

HCC sub-class S2

HCC sub-class S3

Intrahepatic cholangiocarcinoma

Primary sarcoma

Patients who underwent FCH PET/CT followed by histopathologic confirmation of the tumor

Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes

Overall Study

Anticoagulants

Micronutrients

Bone Density Conservation Agents

Edetic Acid

Pentetic Acid

Antidotes

Protective Agents

Chelating Agents

Iron

Iron Chelating Agents

Calcium

Calcium, Dietary

Patients receive gadoxetate disodium IV and then undergo enhanced liver MRI.

Gadoxetate Disodium

Magnetic Resonance Imaging

Gilbert Whang

This pilot clinical trial studies magnetic resonance imaging (MRI) with gadoxetate disodium in measuring tumors in patients with liver cancer. Diagnostic procedures, such as MRI with gadoxetate disodium, may help find and diagnose liver cancer and find out how far the disease has spread. It is not yet known whether MRI with gadoxetate disodium provides a more precise measurement of liver tumors than standard computed tomography (CT).

PRIMARY OBJECTIVES:

I. To evaluate the precision of gadoxetate (gadoxetate disodium)-enhanced MRI in evaluating lesion size.

II. To evaluate if there is a subjective improvement in the delineation of hepatocellular carcinoma (HCC) in the hepatocellular phase of contrast administration.

III. To further assess the sensitivity of gadoxetate-enhanced MRI for the detection of HCC.

SECONDARY OBJECTIVES:

I. To evaluate the reproducibility of various tumor measurement techniques in the evaluation of HCC.

II. To further evaluate how administration of gadoxetate affects diffusion weighted imaging.

OUTLINE:

Patients receive gadoxetate disodium intravenously (IV) and then undergo enhanced liver MRI.

After completion of study, patients are followed up at 2, 4, 8, and 12 months.

MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

MR Techniques in the Evaluation of Hepatocellular Carcinoma: Gadoxetate

Initially, a random effects analysis of variance (ANOVA) will be performed for each type of image (CT vs. MRI), for each phase (4 for CT and 5 for MRI) and for each method of measuring "size" (1-, 2-, and 3-dimensional) - for a total of 27 ANOVAs. Lesion, radiologist, and replication (for the 20 target lesions measured twice) will all be random effects; the inter-reader and the intra-reader variability will be estimated from these models and 95% confidence intervals will be constructed.

ADC values will be recorded for uninvolved liver parenchyma and for tumors before and after administration of gadoxetate disodium.

University of Southern California

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PET/CT in Diagnosing Patients With Liver Cancer Undergoing Surgical Resection	NCT01395030	Adult Hepatocel... Localized Resec...	Computed Tomogr... 18F-fluoromethy... Positron Emissi...	19 Years -	Queen's Medical Center
MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer	NCT02578602	Adult Hepatocel... Advanced Adult ... BCLC Stage 0 Ad... BCLC Stage A Ad... BCLC Stage B Ad... BCLC Stage C Ad... BCLC Stage D Ad... Localized Non-R... Localized Resec...	Gadoxetate Diso... Magnetic Resona...	18 Years -	University of Southern California

Spots Global Cancer Trial Database for localized resectable adult liver carcinoma