Hepatocellular Carcinoma
Conditions
Keywords
CT perfusion, Hepatocellular Carcinoma, Xenetix, Contrast agent
Brief summary
The purpose of this study is to prospectively determine the diagnostic value of Xenetix-CT perfusion for the discrimination between well-differentiated hepatocellular carcinomas (HCC) and poorly/moderately differentiated HCC, in histo-pathologically proven HCC, and with the aim to cover the entire liver.
Interventions
DRUGXenetix-CT perfusion imaging
Injection of 50 ml of Xenetix
Sponsors
Guerbet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed for HCC and planned for surgery (lobectomy or transplantation) within a timeframe of 30 days between first imaging procedure used for the study and surgery.
Exclusion criteria
* Subjects who have undergone prior TACE (TransArterial Chemo Embolization), prior RFA (Radio Frequency Ablation) or prior SIRT (Selected Internal Radio Therapy) within one year before inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Volume (BV) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
| Blood Flow (BF) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
| Permeability Surface (PS) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Portal Venous Liver Perfusion (PVP) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
| Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase) | Within a week from CT perfusion to surgery | Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category. |
| Blood Volume According to Immunohistochemistry Parameter (CD31) | Within a week from CT perfusion to surgery | CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category. |
| Total Liver Perfusion (TLP) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. TLP = ALP + PVP |
| Blood Flow According to Immunohistochemistry Parameter (CD31) | Within a week from CT perfusion to surgery | CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category. |
| Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase) | Within a week from CT perfusion to surgery | Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category. |
| Permeability Surface According to Immunohistochemistry Parameter (CD31) | Within a week from CT perfusion to surgery | CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category. |
| Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase) | Within a week from CT perfusion to surgery | Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category. |
| Hepatic Perfusion Index (HPI) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
| Arterial Liver Perfusion (ALP) According to Degree of Lesions Differentiation | Within a week from CT perfusion to surgery | The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. |
Countries
Austria, Germany, South Korea, Switzerland
Participant flow
Recruitment details
A total of 96 patients were enrolled in 4 countries: Austria, Germany, South Korea and Switzerland.
Participants by arm
| Arm | Count |
|---|---|
| All Included Patients All patients included in the study. | 96 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other reason | 7 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | All Included Patients |
|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment Austria | 3 participants |
| Region of Enrollment Germany | 2 participants |
| Region of Enrollment Korea, Republic of | 85 participants |
| Region of Enrollment Switzerland | 6 participants |
| Severity of cirrhosis (Child-Pugh score) Class A | 79 Participants |
| Severity of cirrhosis (Child-Pugh score) Class B | 8 Participants |
| Severity of cirrhosis (Child-Pugh score) Class C | 2 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 84 |
| serious Total, serious adverse events | 0 / 84 |
Outcome results
Primary
Blood Flow (BF) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Blood Flow (BF) According to Degree of Lesions Differentiation | 73.042 mL/100 grams/min | Standard Deviation 21.551 |
| Moderately/Poorly Differentiated Lesions | Blood Flow (BF) According to Degree of Lesions Differentiation | 72.051 mL/100 grams/min | Standard Deviation 31.792 |
Primary
Blood Volume (BV) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Blood Volume (BV) According to Degree of Lesions Differentiation | 15.930 mL/100 grams | Standard Deviation 6.663 |
| Moderately/Poorly Differentiated Lesions | Blood Volume (BV) According to Degree of Lesions Differentiation | 13.958 mL/100 grams | Standard Deviation 5.315 |
Primary
Permeability Surface (PS) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Permeability Surface (PS) According to Degree of Lesions Differentiation | 26.421 mL/100 grams/min | Standard Deviation 10.014 |
| Moderately/Poorly Differentiated Lesions | Permeability Surface (PS) According to Degree of Lesions Differentiation | 27.750 mL/100 grams/min | Standard Deviation 9.425 |
Secondary
Arterial Liver Perfusion (ALP) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Arterial Liver Perfusion (ALP) According to Degree of Lesions Differentiation | 43.234 mL/min/100 mL | Standard Deviation 16.989 |
| Moderately/Poorly Differentiated Lesions | Arterial Liver Perfusion (ALP) According to Degree of Lesions Differentiation | 42.967 mL/min/100 mL | Standard Deviation 16.678 |
Secondary
Blood Flow According to Immunohistochemistry Parameter (CD31)
CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderately/Poorly Differentiated Lesions | Blood Flow According to Immunohistochemistry Parameter (CD31) | 70.057 mL/100 grams/min | Standard Deviation 25.317 |
| Glutamine Synthetase 10-50% | Blood Flow According to Immunohistochemistry Parameter (CD31) | 75.206 mL/100 grams/min | Standard Deviation 28.519 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.419595% CI: [0.9, 1.29]Regression, Logistic
Secondary
Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase)
Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase) | 79.178 mL/100 grams/min | Standard Deviation 32.656 |
| Glutamine Synthetase 10-50% | Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase) | 61.804 mL/100 grams/min | Standard Deviation 22.087 |
| Glutamine Synthetase >50% | Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase) | 74.261 mL/100 grams/min | Standard Deviation 27.619 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.348795% CI: [0.71, 1.13]Regression, Logistic
Secondary
Blood Volume According to Immunohistochemistry Parameter (CD31)
CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderately/Poorly Differentiated Lesions | Blood Volume According to Immunohistochemistry Parameter (CD31) | 14.708 mL/100 grams | Standard Deviation 7.657 |
| Glutamine Synthetase 10-50% | Blood Volume According to Immunohistochemistry Parameter (CD31) | 15.589 mL/100 grams | Standard Deviation 4.561 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.535495% CI: [0.77, 1.66]Regression, Logistic
Secondary
Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase)
Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase) | 14.994 mL/100 grams | Standard Deviation 5.714 |
| Glutamine Synthetase 10-50% | Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase) | 12.964 mL/100 grams | Standard Deviation 5.268 |
| Glutamine Synthetase >50% | Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase) | 15.551 mL/100 grams | Standard Deviation 6.328 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.247695% CI: [0.47, 1.21]Regression, Logistic
Secondary
Hepatic Perfusion Index (HPI) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Hepatic Perfusion Index (HPI) According to Degree of Lesions Differentiation | 75.232 percentage | Standard Deviation 18.458 |
| Moderately/Poorly Differentiated Lesions | Hepatic Perfusion Index (HPI) According to Degree of Lesions Differentiation | 80.834 percentage | Standard Deviation 14.503 |
Secondary
Permeability Surface According to Immunohistochemistry Parameter (CD31)
CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of CD31 labelling, lesions were classified in the CD31 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderately/Poorly Differentiated Lesions | Permeability Surface According to Immunohistochemistry Parameter (CD31) | 25.434 mL/100 grams/min | Standard Deviation 9.721 |
| Glutamine Synthetase 10-50% | Permeability Surface According to Immunohistochemistry Parameter (CD31) | 28.587 mL/100 grams/min | Standard Deviation 9.832 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.175395% CI: [0.86, 2.31]Regression, Logistic
Secondary
Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase)
Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype. Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and \>50%. In case of absence of glutamine synthetase labelling, lesions were classified in the glutamine synthetase 0% category.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase) | 28.896 mL/100 grams/min | Standard Deviation 7.207 |
| Glutamine Synthetase 10-50% | Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase) | 24.840 mL/100 grams/min | Standard Deviation 6.769 |
| Glutamine Synthetase >50% | Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase) | 27.139 mL/100 grams/min | Standard Deviation 10.714 |
Comparison: Multinomial logistic regression analyses were performed with each off-site CT perfusion parameters as explicative variables taken alone and each off-site immunohistochemistry categorized parameters as dependent variables.p-value: 0.712795% CI: [0.53, 1.54]Regression, Logistic
Secondary
Portal Venous Liver Perfusion (PVP) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Portal Venous Liver Perfusion (PVP) According to Degree of Lesions Differentiation | 19.492 mL/min/100 mL | Standard Deviation 14.586 |
| Moderately/Poorly Differentiated Lesions | Portal Venous Liver Perfusion (PVP) According to Degree of Lesions Differentiation | 13.708 mL/min/100 mL | Standard Deviation 13.207 |
Secondary
Total Liver Perfusion (TLP) According to Degree of Lesions Differentiation
The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site. TLP = ALP + PVP
Time frame: Within a week from CT perfusion to surgery
Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as well differentiated, 42 had lesions assessed as moderately/poorly differentiated and 3 had lesions assessed as well differentiated and moderately/poorly differentiated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Well Differentiated Lesions | Total Liver Perfusion (TLP) According to Degree of Lesions Differentiation | 62.725 mL/min/100 mL | Standard Deviation 15.62 |
| Moderately/Poorly Differentiated Lesions | Total Liver Perfusion (TLP) According to Degree of Lesions Differentiation | 56.674 mL/min/100 mL | Standard Deviation 20.494 |