Trial Outcomes & Findings for PET/CT in Diagnosing Patients With Liver Cancer Undergoing Surgical Resection (NCT NCT01395030)

NCT ID: NCT01395030

Last Updated: 2018-09-26

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

Up to study completion at an average of 2.5 years

Results posted on

2018-09-26

Participant Flow

Participant milestones

Participant milestones
Measure
18F-fluoromethylcholine PET/CT
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
Overall Study
STARTED
64
Overall Study
Complete FCH PET/CT
57
Overall Study
Adequate Tissue for Analysis
50
Overall Study
COMPLETED
57
Overall Study
NOT COMPLETED
7

Reasons for withdrawal

Reasons for withdrawal
Measure
18F-fluoromethylcholine PET/CT
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
Overall Study
Did not complete FCH PET/CT
7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
18F-fluoromethylcholine PET/CT
n=57 Participants
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
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
37 Participants
n=5 Participants
Age, Categorical
>=65 years
20 Participants
n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
Sex: Female, Male
Male
43 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
56 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
29 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
13 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=5 Participants
Race (NIH/OMB)
White
13 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
57 Participants
n=5 Participants
Tumor Diagnosis
Hepatocellular carcinoma
48 Participants
n=5 Participants
Tumor Diagnosis
Cholangiocarcinoma
8 Participants
n=5 Participants
Tumor Diagnosis
Sarcoma
1 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
18F-fluoromethylcholine PET/CT
n=50 Participants
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
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
18F-fluoromethylcholine PET/CT
n=50 Participants
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
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
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 outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
18F-fluoromethylcholine PET/CT
n=41 Participants
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
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
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
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
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
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
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

PRIMARY outcome

Timeframe: Up to 1 year

Population: Number of subjects with available peri-tumoral liver histopathology data

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.

Outcome measures

Outcome measures
Measure
18F-fluoromethylcholine PET/CT
n=48 Participants
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
Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage
Fibrosis stage >= F1
3.03 odds ratio
Interval 1.59 to 5.88
Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage
Fibrosis stage >= F2
5.29 odds ratio
Interval 1.79 to 7.69
Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage
Fibrosis stage >= F3
5.56 odds ratio
Interval 1.85 to 16.7
Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage
Fibrosis stage F4
6.67 odds ratio
Interval 1.33 to 33.3

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
18F-fluoromethylcholine PET/CT
n=50 Participants
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
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
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
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
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
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
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
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
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
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
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

Adverse Events

18F-fluoromethylcholine PET/CT

Serious events: 2 serious events
Other events: 0 other events
Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure
18F-fluoromethylcholine PET/CT
n=64 participants at risk
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
Surgical and medical procedures
death within 30 days
3.1%
2/64 • Number of events 2 • 30 days

Other adverse events

Adverse event data not reported

Additional Information

Program Director for PET Research

The Queen's Medical Center

Phone: 808-691-5466

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place