Liver Neoplasms
Conditions
Brief summary
The purpose of this study is to demonstrate the superiority of SonoVue®-enhanced ultrasound versus unenhanced ultrasound for characterization of Focal Liver Lesions using final diagnosis based on histology or combined imaging/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-enhanced ultrasound
Contrast-enhanced ultrasound (CE-US) examination of the target lesion. Drug: SonoVue® Dose of 2.4 mL bolus injection administered intravenously. Maximum of 2 injections (4.8 mL)
OTHERUnenhanced ultrasound
-Unenhanced: Gray scale and Doppler (color or power imaging) ultrasound investigations of the target lesion. Drug: None
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 focal liver lesion (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 contrast-enhanced (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 beta-human chorionic gonadotropin (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 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 the truth standard. Truth standard: contrast-enhanced computed tomography (CE CT) and /or contrast-enhanced magnetic resonance imaging (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 Malignant 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 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 Malignant 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 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 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 | The 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 the truth standard. True negative: subject with a target lesion characterized as benign 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 and true negative lesions/number of total lesions per truth standard) x 100. |
| Inter-reader Agreement | 24 hours to 6 months | Inter-reader agreement of assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. 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. 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 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 ultrasound) x 100. |
Countries
United States
Participant flow
Recruitment details
Study Initiation Date (first subject enrolled): 30 September 2009; Study completion date (last patient completed study related activities): 29 January 2013. The study was conducted at 14 investigational sites throughout the United States (USA) and 1 site in Europe.
Pre-assignment details
A total of 74 patients received SonoVue in the training phase and were included only in safety population. A total of 263 patients received SonoVue in the efficacy phase. The 74 patients, included within the Not Completed category below, are the training patients.
Participants by arm
| Arm | Count |
|---|---|
| ITD Population All patients who received SonoVue and enrolled in the efficacy phase, had a definite final diagnosis from truth standard and unenhanced and SonoVue-enhanced ultrasonography available | 240 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Indeterminate diagnosis from truth stand | 17 |
| Overall Study | No study drug administered | 12 |
| Overall Study | no truth standard procedure available | 5 |
| Overall Study | Technically inadequate truth standard | 1 |
| Overall Study | Training Patients | 74 |
Baseline characteristics
| Characteristic | ITD Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 50 Participants |
| Age, Categorical Between 18 and 65 years | 190 Participants |
| Race/Ethnicity, Customized Asian | 15 participants |
| Race/Ethnicity, Customized Black | 32 participants |
| Race/Ethnicity, Customized Other | 32 participants |
| Race/Ethnicity, Customized White | 161 participants |
| Region of Enrollment Europe | 15 participants |
| Region of Enrollment United States | 225 participants |
| Sex: Female, Male Female | 117 Participants |
| Sex: Female, Male Male | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 337 |
| serious Total, serious adverse events | 5 / 337 |
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 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 the truth standard. Truth standard: contrast-enhanced computed tomography (CE CT) and /or contrast-enhanced magnetic resonance imaging (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 the 240 ITD participants, only 124 participants (lesions) were malignant based on the 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 | 53.2 Percentage of true positive lesions |
| Offsite Reader 1 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 64.5 Percentage of true positive lesions |
| Offsite Reader 2 - UE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 41.1 Percentage of true positive lesions |
| Offsite Reader 2 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 60.5 Percentage of true positive lesions |
| Offsite Reader 3 UE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 66.1 Percentage of true positive lesions |
| Offsite Reader 3 SonoVue CE-US | Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard | 46.8 Percentage of true positive lesions |
p-value: 0.075495% CI: [-1, 23.6]McNemar
p-value: 0.001195% CI: [8.3, 30.5]McNemar
p-value: 0.001695% CI: [-30.9, -7.8]McNemar
Primary
Specificity: Percentage of True Negative Lesions Among All Malignant 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 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 240 ITD participants, only 116 participants (lesions) were benign based on the truth standard and were included for specificity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Offsite Reader 1 - UE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 24.1 Percentage of true negative lesions |
| Offsite Reader 1 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 71.6 Percentage of true negative lesions |
| Offsite Reader 2 - UE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 6.9 Percentage of true negative lesions |
| Offsite Reader 2 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 67.2 Percentage of true negative lesions |
| Offsite Reader 3 UE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 58.6 Percentage of true negative lesions |
| Offsite Reader 3 SonoVue CE-US | Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard | 87.9 Percentage of true negative lesions |
p-value: <0.000195% CI: [37.4, 57.4]McNemar
p-value: <0.000195% CI: [50.5, 70.2]McNemar
p-value: <0.000195% CI: [19.7, 38.9]McNemar
Secondary
Accuracy: Percentage of True Positive and True Negative Among All Lesions
The 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 the truth standard. True negative: subject with a target lesion characterized as benign 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 and true negative lesions/number of total lesions per truth standard) x 100.
Time frame: 24 hours to 6 months
Population: 240 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 | 39.2 Percent true positive and negative lesio |
| Offsite Reader 1 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 67.9 Percent true positive and negative lesio |
| Offsite Reader 2 - UE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 24.6 Percent true positive and negative lesio |
| Offsite Reader 2 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 63.8 Percent true positive and negative lesio |
| Offsite Reader 3 UE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 62.5 Percent true positive and negative lesio |
| Offsite Reader 3 SonoVue CE-US | Accuracy: Percentage of True Positive and True Negative Among All Lesions | 66.7 Percent true positive and negative lesio |
p-value: <0.000195% CI: [20.5, 37]McNemar
p-value: <0.000195% CI: [31.3, 47.1]McNemar
p-value: 0.317395% CI: [-4, 12.3]McNemar
Secondary
Inter-reader Agreement
Inter-reader agreement of assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. 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 | 32.1 Percent of total number of lesions |
| Offsite Reader 1 - UE-US | Inter-reader Agreement | % Agreement: 2 out of 3 off-site readers agree | 97.1 Percent of total number of lesions |
| Offsite Reader 1 SonoVue CE-US | Inter-reader Agreement | % Agreement: All 3 off-site readers agree | 51.7 Percent of total number of lesions |
| Offsite Reader 1 SonoVue CE-US | Inter-reader Agreement | % Agreement: 2 out of 3 off-site readers agree | 91.7 Percent of total number of lesions |
Secondary
Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant 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 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 ultrasound) x 100.
Time frame: 24 hours to 6 months
Population: Among the 240 ITD participants, the overall 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 Malignant Lesions Per Ultrasound | 32.6 Percent negative lesions by ultrasound |
| Offsite Reader 1 SonoVue CE-US | Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound | 65.4 Percent negative lesions by ultrasound |
| Offsite Reader 2 - UE-US | Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound | 9.9 Percent negative lesions by ultrasound |
| Offsite Reader 2 SonoVue CE-US | Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound | 61.4 Percent negative lesions by ultrasound |
| Offsite Reader 3 UE-US | Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound | 61.8 Percent negative lesions by ultrasound |
| Offsite Reader 3 SonoVue CE-US | Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound | 60.7 Percent negative lesions by ultrasound |
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
p-value: 0.761Wald 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 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 ultrasound) x 100.
Time frame: 24 hours to 6 months
Population: Among the 240 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 | 42.9 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 | 70.8 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 | 32.1 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 | 66.4 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 | 63.1 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 | 80.6 Percent positive lesions by ultrasound |
p-value: <0.0001Wald Test
p-value: <0.0001Wald Test
p-value: 0.0004Wald 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. 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 116 ITD participants with benign lesions based on the truth standard, only 89 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 | # of Hemangioma by Truth Standard | 64 Benign lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 21 Benign lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 0 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 47 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 64 Benign lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 10 Benign lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 2 Benign lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 2 Benign lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 64 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 64 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 13 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 40 Benign lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 0 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 36 Benign lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 64 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # Hemangioma Correctly Characterized | 50 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Focal nodular hyperplasia by Truth Standard | 25 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | #Focal nodular hyperplasia Correctly Characterized | 12 Benign lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Benign FLLs | # of Hemangioma by Truth Standard | 64 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 124 ITD participants with malignant lesions based on the truth standard, only 115 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 | 84 Malignant lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 29 Malignant lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 1 - UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 14 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 33 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 84 Malignant lesions |
| Offsite Reader 1 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 20 Malignant lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 16 Malignant lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 12 Malignant lesions |
| Offsite Reader 2 - UE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 84 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 84 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 17 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 13 Malignant lesions |
| Offsite Reader 2 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 19 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 21 Malignant lesions |
| Offsite Reader 3 UE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 84 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # HCC(Malignant) Correctly Characterized | 20 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of Metastasis by Truth Standard | 31 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # Metastasis Correctly Characterized | 21 Malignant lesions |
| Offsite Reader 3 SonoVue CE-US | Specific Diagnosis of Malignant FLLs | # of HCC by Truth Standard | 84 Malignant lesions |