Liver Neoplasms
Conditions
Brief summary
The purpose of this study is to demonstrate the Sensitivity and Specificity of SonoVue®-enhanced ultrasound is superior to that of unenhanced ultrasound for the characterization of benign versus malignant FLLs using final diagnosis based on histology or combined imaging (CE-CT and/or CE MRI)/clinical data as truth standard.
Detailed description
Unit of analysis for the outcome measures was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized.
Interventions
DRUGSonoVue®
SonoVue (2.4 mL)
Sponsors
Bracco Diagnostics, Inc
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
* Male/female. * Provides written Informed Consent and is willing to comply with protocol requirements. * Is at least 18 years of age. * Has at least 1 FLL (target lesion) requiring work-up for characterization. Target lesions may include those: Incidentally detected, In subjects with chronic hepatitis or liver cirrhosis, In subjects with known history of malignancy. * Is scheduled for surgical removal or biopsy of the target lesion from 24 hours to 30 days after the SonoVue® administration OR * In case tissue biopsy is not indicated nor surgery planned, is scheduled for or has performed a CE-CT and/or CE-MRI of the target lesion from 30 days to 48 hours prior to or from 24 hours to 30 days after the administration of SonoVue®.
Exclusion criteria
* Has an acoustic window insufficient for adequate ultrasound examination of the liver. * Has a FLL that cannot be identified with unenhanced ultrasound. * Has received or is scheduled for antineoplastic chemotherapy or an invasive procedure in the time period between test procedures and truth standard assessments which may have modified the target lesion. * Is receiving any other contrast medium, within the 48 hours before and up to 24 hours following the administration of SonoVue®. * Has previously been enrolled in and completed this study. * Known right to left cardiac shunt, bidirectional or transient. * Has any known allergy to 1 or more of the ingredients of the investigational product (sulfur hexafluoride or to any components of SonoVue®). * Has any contraindication to 1 of the planned imaging procedures (ultrasound, CT or MRI), e.g., implants, claustrophobia, inadequate medical conditions etc. * Has received an investigational compound within 30 days before admission into this study. * Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations. * Is determined by the Investigator that the subject is clinically unsuitable for the study. * Is a pregnant or lactating female. Exclude the possibility of pregnancy by: testing on site at the institution serum βHCG within 24 hours prior to the start of SonoVue® administration, surgical history (e.g., tubal ligation or hysterectomy), post menopausal with a minimum 1 year without menses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 24 hours to 6 months | Sensitivity of SonoVue-enhanced ultrasound (SonoVue CE-US) versus unenhanced ultrasound (UE-US) for characterization of malignant focal liver lesions (FLLs) using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the Intent-to-diagnose (ITD) population. Unit of analysis was the lesion, equivalent to subject, since each subject had a single lesion to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. Truth standard: CE-CT and/or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up Calculated as (number of true positive lesions/number of malignant lesions per truth standard) x 100 |
| Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 24 hours to 6 months | Specificity of SonoVue-enhanced versus unenhanced ultrasound for characterization of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Among the 259 ITD participants, only 140 participants (lesions) were benign based on the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per truth standard) x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 24 hours to 6 months | Negative Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per ultrasound) x 100. |
| Specific Diagnosis of Malignant FLLs | 24 hours to 6 months | SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of malignant FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100. |
| Accuracy: Percentage of True Positive and True Negative Among All Lesions | 24 hours to 6 months | Accuracy of SonoVue-enhanced versus unenhanced ultrasound for characterization of malignant and benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and truth standard. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive and true negative lesions/number of total lesions per truth standard) x 100. |
| Inter-reader Agreement | 24 hours to 6 months | Kappa statistic based on assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately and computation for the percentage agreement within two categories: 3 out of 3 readers agree and 2 out of 3 readers agree. |
| Specific Diagnosis of Benign FLLs | 24 hours to 6 months | SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Among the 140 ITD participants with benign lesions based on the truth standard, only 91 participants (lesions) were characterized as either hemangioma or focal nodular hyperplasia. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100. |
| Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 24 hours to 6 months | Positive Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive lesions/number of malignant lesions per ultrasound) x 100. |
Countries
United States
Participant flow
Recruitment details
Study Initiation Date (first subject enrolled): 15 June 2010; Study completion date (last patient completed study related activities): 18 February 2013. The study was conducted at 18 investigational sites; 11 sites throughout the United States (USA), 5 sites in Europe, and 2 sites in Canada.
Pre-assignment details
A total of 67 patients received SonoVue in the training phase and were included only in safety population. A total of 259 patients received SonoVue in the efficacy phase. The 67 patients, included within the Not Completed category below, are the training patients.
Participants by arm
| Arm | Count |
|---|---|
| ITD Population All patients who were enrolled in the efficacy phase, received SonoVue, had a definite final diagnosis from truth standard and unenhanced and SonoVue-enhanced ultrasonography available | 259 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Indeterminate diagnosis from truth stand | 3 |
| Overall Study | No study drug admimnistered | 13 |
| Overall Study | No truth standard procedure available | 9 |
| Overall Study | Technically inadequate truth standard | 2 |
| Overall Study | Training Patients | 67 |
Baseline characteristics
| Characteristic | ITD Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 74 Participants |
| Age, Categorical Between 18 and 65 years | 185 Participants |
| Age, Continuous | 56.9 years STANDARD_DEVIATION 13.4 |
| Race/Ethnicity, Customized Asian | 12 participants |
| Race/Ethnicity, Customized Black | 22 participants |
| Race/Ethnicity, Customized Other | 19 participants |
| Race/Ethnicity, Customized White | 206 participants |
| Region of Enrollment Canada | 34 participants |
| Region of Enrollment Europe | 93 participants |
| Region of Enrollment United States | 132 participants |
| Sex: Female, Male Female | 123 Participants |
| Sex: Female, Male Male | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 340 |
| serious Total, serious adverse events | 4 / 340 |
Outcome results
Primary
Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard
Sensitivity of SonoVue-enhanced ultrasound (SonoVue CE-US) versus unenhanced ultrasound (UE-US) for characterization of malignant focal liver lesions (FLLs) using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the Intent-to-diagnose (ITD) population. Unit of analysis was the lesion, equivalent to subject, since each subject had a single lesion to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. Truth standard: CE-CT and/or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up Calculated as (number of true positive lesions/number of malignant lesions per truth standard) x 100
Time frame: 24 hours to 6 months
Population: Among 259 ITD subjects, 119 were malignant by truth standard and were included for sensitivity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 UE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 48.7 Percentage of true positive lesions |
| Offsite Reader 1 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 86.6 Percentage of true positive lesions |
| Offsite Reader 2 UE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 35.3 Percentage of true positive lesions |
| Offsite Reader 2 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 75.6 Percentage of true positive lesions |
| Offsite Reader 3 UE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 16.0 Percentage of true positive lesions |
| Offsite Reader 3 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 91.6 Percentage of true positive lesions |
p-value: <0.000195% CI: [27.4, 48.2]McNemar
p-value: <0.000195% CI: [30.4, 50.3]McNemar
p-value: <0.000195% CI: [67.9, 83.3]McNemar
Primary
Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard'
Specificity of SonoVue-enhanced versus unenhanced ultrasound for characterization of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Among the 259 ITD participants, only 140 participants (lesions) were benign based on the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per truth standard) x 100.
Time frame: 24 hours to 6 months
Population: Among the 259 ITD participants, only 140 participants (lesions) were benign based on the truth standard and were were included for specificty.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 UE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 62.9 Percentage of true benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 70.7 Percentage of true benign lesions |
| Offsite Reader 2 UE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 54.3 Percentage of true benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 82.9 Percentage of true benign lesions |
| Offsite Reader 3 UE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 22.1 Percentage of true benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard' | 72.9 Percentage of true benign lesions |
p-value: 0.13895% CI: [-2.4, 18.2]McNemar
p-value: <0.000195% CI: [19.7, 37.5]McNemar
p-value: <0.000195% CI: [42, 59.5]McNemar
Secondary
Accuracy: Percentage of True Positive and True Negative Among All Lesions
Accuracy of SonoVue-enhanced versus unenhanced ultrasound for characterization of malignant and benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and truth standard. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive and true negative lesions/number of total lesions per truth standard) x 100.
Time frame: 24 hours to 6 months
Population: 259 participants in the ITD population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 UE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 56.4 Percent true positive and negative lesio |
| Offsite Reader 1 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 78.0 Percent true positive and negative lesio |
| Offsite Reader 2 UE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 45.6 Percent true positive and negative lesio |
| Offsite Reader 2 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 79.5 Percent true positive and negative lesio |
| Offsite Reader 3 UE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 19.3 Percent true positive and negative lesio |
| Offsite Reader 3 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 81.5 Percent true positive and negative lesio |
p-value: <0.000195% CI: [14.1, 29.2]McNemar
p-value: <0.000195% CI: [27.3, 40.7]McNemar
p-value: <0.000195% CI: [67.9, 83.3]McNemar
Secondary
Inter-reader Agreement
Kappa statistic based on assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately and computation for the percentage agreement within two categories: 3 out of 3 readers agree and 2 out of 3 readers agree.
Time frame: 24 hours to 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Offsite Reader 1 UE-US | Inter-reader Agreement | % Agreement: All 3 off-site readers agree | 28.2 Percentage of agreement |
| Offsite Reader 1 UE-US | Inter-reader Agreement | % Agreement: 2 out of 3 off-site readers agree | 94.6 Percentage of agreement |
| Offsite Reader 1 SonoVue CE-US | Inter-reader Agreement | % Agreement: All 3 off-site readers agree | 66.0 Percentage of agreement |
| Offsite Reader 1 SonoVue CE-US | Inter-reader Agreement | % Agreement: 2 out of 3 off-site readers agree | 99.6 Percentage of agreement |
Secondary
Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound
Negative Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per ultrasound) x 100.
Time frame: 24 hours to 6 months
Population: Among the 259 ITD participants, the number of participants (lesions) assessed as benign varied based on the evaluation of the UE-US and CE-US made by each off-site Reader.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 UE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 59.1 Percent negative lesions by ultrasound |
| Offsite Reader 1 SonoVue CE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 86.1 Percent negative lesions by ultrasound |
| Offsite Reader 2 UE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 49.7 Percent negative lesions by ultrasound |
| Offsite Reader 2 SonoVue CE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 80.0 Percent negative lesions by ultrasound |
| Offsite Reader 3 UE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 23.7 Percent negative lesions by ultrasound |
| Offsite Reader 3 SonoVue CE-US | Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound | 91.1 Percent negative lesions by ultrasound |
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
Secondary
Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound
Positive Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive lesions/number of malignant lesions per ultrasound) x 100.
Time frame: 24 hours to 6 months
Population: Among the 259 ITD participants, the overall number of participants (lesions) assessed as malignant varied based on the evaluation of the UE-US and CE-US made by each off-site Reader.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 UE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 52.7 Percent positive lesions by ultrasound |
| Offsite Reader 1 SonoVue CE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 71.5 Percent positive lesions by ultrasound |
| Offsite Reader 2 UE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 39.6 Percent positive lesions by ultrasound |
| Offsite Reader 2 SonoVue CE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 78.9 Percent positive lesions by ultrasound |
| Offsite Reader 3 UE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 14.8 Percent positive lesions by ultrasound |
| Offsite Reader 3 SonoVue CE-US | Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound | 74.1 Percent positive lesions by ultrasound |
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
Secondary
Specific Diagnosis of Benign FLLs
SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Among the 140 ITD participants with benign lesions based on the truth standard, only 91 participants (lesions) were characterized as either hemangioma or focal nodular hyperplasia. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100.
Time frame: 24 hours to 6 months
Population: Among the 140 ITD participants with benign lesions based on the truth standard, only 91 participants (lesions) were characterized as either hemangioma or focal nodular hyperplasia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Offsite Reader 1 UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 15 Benign lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 28 Benign lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 38 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 23 Benign lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 30 Benign lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 8 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 43 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 22 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 2 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 12 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 18 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 39 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 38 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 52 Benign lesions |
Secondary
Specific Diagnosis of Malignant FLLs
SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of malignant FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100.
Time frame: 24 hours to 6 months
Population: Among the 119 ITD participants with malignant lesions based on the truth standard, only 94 participants (lesions) were characterized as either hepatocellular carcinoma (HCC) lesions or metastatic lesions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Offsite Reader 1 UE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 18 Malignant lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 1 UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 16 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 26 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 37 Malignant lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 12 Malignant lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 10 Malignant lesions |
| Offsite Reader 2 UE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 31 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 29 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 3 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 1 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 47 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 30 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 47 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 28 Malignant lesions |