Ultrasound Elastography of Breast Lesions | NCT00716482

Ultrasound Elastography of Breast Lesions | NCT00716482 | Trialant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Estimates of Effect of Selectively Upgrading BIRADS Category 3 and Downgrading BIRADS 4a Masses Based on SWE Features. Overall Specificity and Sensitivity of BI-RADS Score Using Conventional B-mode Ultrasound vs. B-mode + Certain SWE Characteristics	Positive reference standard = malignant cytologic or histopathologic result. Negative reference standard = BIRADS 2 lesions, BIRADS 3 lesions with benign histopathology, or a 1 year follow-up ultrasound exam showing resolved or decreased lesion size. Conservative strategy:features of E-homogeneity, E-max and E-color were used to upgrade BIRADS 3 lesions to BIRADS 4a' or downgrade BIRADS 4a lesions to BIRADS 3'. Aggressive strategy used the same features but upgraded and downgraded more lesions. Based on 939 lesions.	2 years

Secondary Outcomes

Measure	Description	Time Frame
Qualitative Intraobserver Reproducibility of SWE Related to Homogeneity Feature	614 benign and 144 malignant breast lesions were scanned in SWE 3 consecutive times, and the similarity of the 3 images was evaluated by the investigator.	performed on the same day, within 2 years from study start date
Intraobserver Reliability of Quantitative SWE Measurements

Contacts/Locations Module

Name	Affiliation	Role
David O Cosgrove, MD	Hammersmith Hospitals NHS Trust	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California - LAC+USC Medical Center, OPD Rm 3P61		Los Angeles	California	90033	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22210408	Result	Cosgrove DO, Berg WA, Dore CJ, Skyba DM, Henry JP, Gay J, Cohen-Bacrie C; BE1 Study Group. Shear wave elastography for breast masses is highly reproducible. Eur Radiol. 2012 May;22(5):1023-32. doi: 10.1007/s00330-011-2340-y. Epub 2011 Dec 31.
22282182	Result	Berg WA, Cosgrove DO, Dore CJ, Schafer FK, Svensson WE, Hooley RJ, Ohlinger R, Mendelson EB, Balu-Maestro C, Locatelli M, Tourasse C, Cavanaugh BC, Juhan V, Stavros AT, Tardivon A, Gay J, Henry JP, Cohen-Bacrie C; BE1 Investigators. Shear-wave elastography improves the specificity of breast US: the BE1 multinational study of 939 masses. Radiology. 2012 Feb;262(2):435-49. doi: 10.1148/radiol.11110640.

ID	Title	Description
FG000	Breast Lesion	B-mode ultrasound examination with currently marketed machine followed by ultrasound B-mode examination and ShearWave Elastography examination

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0001681 subjects
COMPLETED		FG0001562 subjects
NOT COMPLETED		FG000119 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0006 subjects
Inadequate acquisition or analysis		FG00050 subjects
no pathology obtained		FG00010 subjects

Baseline Characteristics Module

ID	Title	Description
BG000	Breast Lesion	B-mode ultrasound examination with currently marketed machine followed by ultrasound B-mode examination and ShearWave Elastography examination

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous	mean age is based on 1681 participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Estimates of Effect of Selectively Upgrading BIRADS Category 3 and Downgrading BIRADS 4a Masses Based on SWE Features. Overall Specificity and Sensitivity of BI-RADS Score Using Conventional B-mode Ultrasound vs. B-mode + Certain SWE Characteristics

Positive reference standard = malignant cytologic or histopathologic result. Negative reference standard = BIRADS 2 lesions, BIRADS 3 lesions with benign histopathology, or a 1 year follow-up ultrasound exam showing resolved or decreased lesion size.

Conservative strategy:features of E-homogeneity, E-max and E-color were used to upgrade BIRADS 3 lesions to BIRADS 4a' or downgrade BIRADS 4a lesions to BIRADS 3'. Aggressive strategy used the same features but upgraded and downgraded more lesions.

Based on 939 lesions.

Per protocol. Analysis includes 289 malignant and 650 benign masses. One lesion was analyzed per participant.

Posted

Number

participants

2 years

ID	Title	Description
OG000	Specificity

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Breast Lesion	B-mode ultrasound examination with currently marketed machine followed by ultrasound B-mode examination and ShearWave Elastography examination

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Research Coordinator	SuperSonic Imagine	+33 442 99 24 24		sharon.bruce@supersonicimagine.fr

Condition Browse Module

ID	Term
D001943	Breast Neoplasms
D009369	Neoplasms

ID	Term
D009371	Neoplasms by Site
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

Region of Enrollment

Number

participants

Title

Denominators

Categories

France

Title	Measurements
	BG000322

United States

Title	Measurements
	BG000566

Germany

Title	Measurements
	BG000529

Italy

Title	Measurements
	BG00089

United Kingdom

Title	Measurements
	BG000175

Title

Denominators

Categories

lesion shape

Title	Measurements
	OG000451 OG001283

lesion homogeneity-conservative strategy

Title	Measurements
	OG000464 OG001280

lesion homogeneity-aggressive strategy

Title	Measurements
	OG000510 OG001278

maximum elasticity (Emax)-conservative strategy

Title	Measurements
	OG000427 OG001286

maximum elasticity (Emax)-aggressive strategy

Title	Measurements
	OG000503 OG001281

median mean elasticity (Emean)

Title	Measurements
	OG000407 OG001285

diameter ration (Edia)

Title	Measurements
	OG000333 OG001286

median elasticity ratio (Erat)

Title	Measurements
	OG000422 OG001284

color score of Emax (Ecol)-conservative strategy

Title	Measurements
	OG000457 OG001288

color score of Emax (Ecol)-aggressive strategy

Title	Measurements
	OG000510 OG001285

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	Tested Non-Inferiority	Non-Inferiority Type
OG000	Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Specificity of lesion shape	0.694	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of the homogeneity of elasticity with the lesion and surrounding tissue using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if they were not homogeneous on the color overlay SW elastographic image; BIRADS 4a mass downgraded to BIRADS 3' if they were very homogeneous). Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Lesion homogeneity spec, conservative	0.714	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of the homogeneity of elasticity with the lesion and surrounding tissue using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if they were not homogeneous on the color overlay SW elastographic image; BIRADS 4a mass downgraded to BIRADS 3' if they were very or reasonably homogeneous). Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Lesion homogeneity spec, agressive	0.785	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of the maximum elasticity using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if maximum elasticity was 160 kiloPascals (kPa) (7.3 m/sec) or more; BIRADS 4a mass downgraded to BIRADS 3' if the maximum elasticity was 30 kPa (3.2 m/sec) or less). Null hypothesis is that there is no difference between the two tests.	McNemar	0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Max. elasticity specificity,conservative	0.657	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of the maximum elasticity using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if maximum elasticity was 160 kPa(7.3 m/sec) or more; BIRADS 4a mass downgraded to BIRADS 3' if the maximum elasticity was 80 kPa (5.2 m/sec) or less). Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Max. elasticity specificity, aggressive	0.774	2-Sided	95	No	Superiority or Other
OG000	Elastography image median mean elasticity value. Null hypothesis is that there is no difference between the two tests.	McNemar	0.18	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	median mean elasticity value specificity	0.626	2-Sided	95	No	Superiority or Other
OG000	Elastography image diameter ratio. Null hypothesis is that there is no difference between the two tests.	McNemar	0.006	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Diameter ratio specificity	0.512	2-Sided	95	No	Superiority or Other
OG000	Elastography image median elasticity ratio. Null hypothesis is that there is no difference between the two tests.	McNemar	0.006	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Median elasticity ratio specificity	0.649	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of color using a six-point color scale of maximum elasticity in the mass and surrounding parenchyma using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if the max stiffness on the color overlay SW elastographic image was red; BIRADS 4a mass downgraded to BIRADS 3' if the max stiffness on the color overlay SW elastographic image was black to dark blue). Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Max.color scale specificity,conservative	0.703	2-Sided	95	No	Superiority or Other
OG000	Elastography image specificity of color using a six-point color scale of maximum elasticity in the mass and surrounding parenchyma using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if the max stiffness on the color overlay SW elastographic image was red; BIRADS 4a mass downgraded to BIRADS 3' if the max stiffness on the color overlay SW elastographic image was black to dark blue, or light blue). Null hypothesis is that there is no difference between the two tests.	McNemar	<0.001	P-value was that to test the null hypothesis that there is no change in specificity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05 Overall specificity = 78.5%	Max. color scale specificity, aggressive	0.785	2-Sided	95	No	Superiority or Other
OG001	Elastography image lesion shape. Null hypothesis is that there is no difference between the two tests.	McNemar	0.48	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Lesion shape sensitivity	0.979	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of the homogeneity of elasticity with the lesion and surrounding tissue using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if they were not homogeneous on the color overlay SW elastographic image; BIRADS 4a mass downgraded to BIRADS 3' if they were very homogeneous). Null hypothesis is that there is no difference between the two tests.	McNemar	0.74	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Lesion homogeneity sens, conservative	0.969	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of the homogeneity of elasticity with the lesion and surrounding tissue using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if they were not homogeneous on the color overlay SW elastographic image; BIRADS 4a mass downgraded to BIRADS 3' if they were very or reasonably homogeneous). Null hypothesis is that there is no difference between the two tests.	McNemar	0.37	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	elasticity homogeneity,aggressive,sensit	0.962	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of the maximum elasticity using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if maximum elasticity was 160 kPa(7.3 m/sec) or more; BIRADS 4a mass downgraded to BIRADS 3' if the maximum elasticity was 30 kPa (3.2 m/sec) or less). Null hypothesis is that there is no difference between the two tests.	McNemar	0.025	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05 Overall sensitivity = 99.0%	elasticity homegeneity,conservative,sens	0.990	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of the maximum elasticity using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if maximum elasticity was 160 kPa(7.3 m/sec) or more; BIRADS 4a mass downgraded to BIRADS 3' if the maximum elasticity was 80 kPa (5.2 m/sec) or less). Null hypothesis is that there is no difference between the two tests.	McNemar	>0.99	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	max. elasticity sensitivity,aggressive	0.972	2-Sided	95	No	Superiority or Other
OG001	Elastography image median mean elasticity value. Null hypothesis is that there is no difference between the two tests.	McNemar	0.046	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	median mean elasticity value sensitivity	0.986	2-Sided	95	No	Superiority or Other
OG001	Elastography image diameter ratio. Null hypothesis is that there is no difference between the two tests.	McNemar	0.025	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	diameter ratio sensitivity	0.990	2-Sided	95	No	Superiority or Other
OG001	Elastography image median elasticity ratio. Null hypothesis is that there is no difference between the two tests.	McNemar	0.083	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	median elasticity ratio sensitivity	0.983	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of color using a six-point color scale of maximum elasticity in the mass and surrounding parenchyma using conservative strategy (BIRADS 3 mass upgraded to BIRADS 4a' if the max stiffness on the color overlay SW elastographic image was red; BIRADS 4a mass downgraded to BIRADS 3' if the max stiffness on the color overlay SW elastographic image was black to dark blue). Null hypothesis is that there is no difference between the two tests.	McNemar	0.008	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Max.color scale sensitivity,conservative	0.997	2-Sided	95	No	Superiority or Other
OG001	Elastography image sensitivity of color using a six-point color scale of maximum elasticity in the mass and surrounding parenchyma using aggressive strategy (BIRADS 3 mass upgraded to BIRADS 4a' if the max stiffness on the color overlay SW elastographic image was red; BIRADS 4a mass downgraded to BIRADS 3' if the max stiffness on the color overlay SW elastographic image was black to dark blue, or light blue). Null hypothesis is that there is no difference between the two tests.	McNemar	0.21	P-value was that to test the null hypothesis that there is no change in sensitivity with addition of the ShearWave elastographic feature. Significance threshold P-value = 0.05	Max. color scale sensitivity, aggressive	0.986	2-Sided	95	No	Superiority or Other

Secondary

Qualitative Intraobserver Reproducibility of SWE Related to Homogeneity Feature

614 benign and 144 malignant breast lesions were scanned in SWE 3 consecutive times, and the similarity of the 3 images was evaluated by the investigator.

Per protocol. One lesion was analyzed per participant.

Posted

Number

participants

performed on the same day, within 2 years from study start date

ID	Title	Description
OG000	Very Homogeneous	The Elastography image of the lesion has a smooth and consistent color appearance throughout, or very subtle color differences relating to small changes on the color scale are observed.
OG001	Reasonably Homogeneous	The Elastography image of the lesion has a slightly "patchy" appearance. The image may consist of larger (2-5mm) sub-regions within the lesion boundary that are homogenous, or the color differences between adjacent areas within the lesion are small.
OG002	Not Homogeneous	The Elastography image of the lesion is inhomogeneous and has a "mottled" or "patchy" appearance throughout.

Units	Counts
Participants	OG000391 OG001212 OG002155

Title

Denominators

Categories

All images very or reasonably similar

Title	Measurements
	OG000385 OG001176 OG002105

Some images similar

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Null hypothesis: no variance of similarity exists between the three groups	Kruskal-Wallis	Kruskal-Wallis one-way ANOVA. Kruskal-Wallis was performed once to get p-values for all of the 9 categories at once.	<0.001							95						No	Superiority or Other

Secondary

Intraobserver Reliability of Quantitative SWE Measurements

614 benign and 144 malignant lesions. Each category's measurement (diameter, area, etc..) is performed 3 times. These 3 measurements are then compared with each other in order to calculate the interclass correlation coefficient.

Per protocol. 758 masses (614 benign and 144 malignant)are analyzed. One lesion was analyzed per participant. 3 acquisitions per lesion were analyzed with the ICC method for 10 different parameters.

Posted

Number

95% Confidence Interval

correlation coefficient

performed on the same day, within 2 years from study start date

ID	Title	Description
OG000	Overall (All Masses)	614 benign and 144 malignant masses

Units	Counts
Participants	OG000758

Title

Denominators

Categories

Diameter

Title	Measurements
	OG0000.94(0.94 to 0.95)

Area

Title	Measurements
	OG0000.95(0.94 to 0.95)

Perimeter

Secondary

Interobserver Agreement of B Mode Ultrasound and SWE Features

614 benign and 144 malignant breast masses.

Per protocol. One lesion was analyzed per participant. Two independent readers did a qualitative assessment of 7 image parameters (per lesion) using Kappa.

Posted

Number

95% Confidence Interval

kappa statistic

performed on the same day, after study completion

ID	Title	Description
OG000	Overall (All Masses)	Benign and malignant lesions

Units	Counts
Participants	OG000758

Title

Denominators

Categories

B-mode shape

Title	Measurements
	OG0000.58(0.51 to 0.65)

B-mode orientation

Title	Measurements
	OG0000.53(0.46 to 0.60)

B-mode margin