Adult Hepatocellular Carcinoma, Localized Resectable Adult Liver Carcinoma
Conditions
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTComputed Tomography
Undergo FCH PET/CT
Undergo FCH PET/CT
DIAGNOSTIC_TESTPositron Emission Tomography
Undergo FCH PET/CT
Sponsors
National Cancer Institute (NCI)
Queen's Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve. | Up to study completion at an average of 2.5 years | 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). |
| Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity | Up to study completion at an average of 2.5 years | 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. |
| Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | Up to study completion at an average of 2.5 years | 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). |
| Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Up to 1 year | 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. |
| Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | Up to study completion at an average of 2.5 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 18F-fluoromethylcholine PET/CT 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 | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not complete FCH PET/CT | 7 |
Baseline characteristics
| Characteristic | 18F-fluoromethylcholine PET/CT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 13 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 57 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 43 Participants |
| Tumor Diagnosis Cholangiocarcinoma | 8 Participants |
| Tumor Diagnosis Hepatocellular carcinoma | 48 Participants |
| Tumor Diagnosis Sarcoma | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 64 |
| other Total, other adverse events | 0 / 64 |
| serious Total, serious adverse events | 2 / 64 |
Outcome results
Primary
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.
Time frame: Up to 1 year
Population: Number of subjects with available peri-tumoral liver histopathology data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-fluoromethylcholine PET/CT | Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Fibrosis stage >= F1 | 3.03 odds ratio |
| 18F-fluoromethylcholine PET/CT | Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Fibrosis stage >= F2 | 5.29 odds ratio |
| 18F-fluoromethylcholine PET/CT | Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Fibrosis stage >= F3 | 5.56 odds ratio |
| 18F-fluoromethylcholine PET/CT | Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage | Fibrosis stage F4 | 6.67 odds ratio |
Primary
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).
Time frame: Up to study completion at an average of 2.5 years
Population: Patients from whom surgical tumor resection (ie. partial hepatectomy) provided adequate tumor and liver samples for tissue analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-fluoromethylcholine PET/CT | Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve. | All primary liver cancers (n=50) | 0.87 unitless |
| 18F-fluoromethylcholine PET/CT | Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve. | HCC only (n=41) | 0.80 unitless |
Primary
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.
Time frame: Up to study completion at an average of 2.5 years
Population: Patients from whom surgical tumor resection (ie. partial hepatectomy) provided adequate tumor and liver samples for tissue analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-fluoromethylcholine PET/CT | Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity | Sensitivity for HCC sub-class S3 | 100 percentage of analyzed participants |
| 18F-fluoromethylcholine PET/CT | Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity | Specificity for HCC sub-class S3 | 73 percentage of analyzed participants |
Primary
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.
Time frame: Up to study completion at an average of 2.5 years
Population: Patients who underwent FCH PET/CT followed by histopathologic confirmation of the tumor
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S1 | High FCH uptake | 7 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S1 | Low FCH uptake | 6 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S2 | High FCH uptake | 0 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S2 | Low FCH uptake | 4 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S3 | High FCH uptake | 24 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | HCC sub-class S3 | Low FCH uptake | 0 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | Intrahepatic cholangiocarcinoma | High FCH uptake | 0 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | Intrahepatic cholangiocarcinoma | Low FCH uptake | 8 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | Primary sarcoma | High FCH uptake | 0 Participants |
| 18F-fluoromethylcholine PET/CT | Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes | Primary sarcoma | Low FCH uptake | 1 Participants |
Primary
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).
Time frame: Up to study completion at an average of 2.5 years
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_OXIDATIVE_PHOSPHORYLATION | 0.009 false discovery rate |
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_ADIPOGENESIS | 0.012 false discovery rate |
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_PEROXISOME | 0.012 false discovery rate |
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_XENOBIOTIC_METABOLISM | 0.014 false discovery rate |
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_FATTY_ACID_METABOLISM | 0.015 false discovery rate |
| 18F-fluoromethylcholine PET/CT | Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. | HALLMARK_BILE_ACID_METABOLISM | 0.016 false discovery rate |