Breast Cancer, Thyroid Cancer
Conditions
Keywords
Cancer Screening
Brief summary
This is a 3-arm single center study of 45 patients. These cohorts will include 15 breast patients scheduled to undergo a biopsy, and 15 thyroid patients scheduled to undergo fine needle aspiration, biopsy, or thyroidectomy that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to their scheduled biopsy. Prior to imaging clinical patients, the third arm will include 15 healthy volunteers that will be imaged to optimize imaging parameters.
Detailed description
Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast or thyroid cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation.
Interventions
DRUGDefinity
Perflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed.
DEVICEAcoustic Angiography
Acoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8). Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.
Sponsors
National Cancer Institute (NCI)
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Healthy Volunteers Inclusion Criteria * Able to provide informed consent * Negative urine pregnancy test in women of child-bearing potential
Exclusion criteria
* Institutionalized subject (prisoner or nursing home patient) * Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD) * Known hypersensitivity to perflutren lipid (Definity®) * Active cardiac disease including any of the following: * Severe congestive heart failure * Unstable angina. * Severe arrhythmia * Myocardial infarction within 14 days prior to the date of proposed Definity® administration. * Pulmonary hypertension * Cardiac shunts Breast Imaging Patients Inclusion Criteria * Women * Patient had a diagnostic breast ultrasound study performed at UNC * Scheduled for a core needle or surgical breast biopsy of at least one breast lesion that is 2 cm or less in size and 3 cm in depth from the skin surface * Able to provide informed consent * Negative urine pregnancy test in women of child-bearing potential * BIRADS score of 4 or 5.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Acoustic Angiography; Breast Imaging | Baseline | The sensitivity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Sensitivity (%) = True Positives (TP)+False Negatives (FN)True Positives (TP) |
| Specificity of Acoustic Angiography; Breast Imaging (Percent of Negative Scans) | Baseline | Specificity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Specificity was calculated based on the formula, which is true negative / (true negative + false positive). |
| Sensitivity of Acoustic Angiography; Thyroid Imaging (Percent of Positive Scans) | Baseline | Sensitivity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available. |
| Specificity of Acoustic Angiography; Thyroid Imaging (Percent of Negative Scans) | Baseline | Specificity of Acoustic Angiography in the analysis of known thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units) | Baseline | To compare (using a reader study) the sensitivity of acoustic angiography to the sensitivity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available. |
| Area Under the Curve of Acoustic Angiography (Arbitrary Units) | Baseline | To compare the area under the curve (AUC) of acoustic angiography to the AUC of the B-mode ultrasound. Readers assigned a malignancy likelihood score from 1 to 5, with 1 likely benign to 5 likely malignant. An AUC was then calculated based on these scores. The Receiver operating curve (ROC ) was then plotted from this curve, and the AUC was estimated from the ROC curve. |
| Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units) | Calculated once all imaging is complete [Anticipated 1.5 years] | To compare (using a reader study) the specificity of acoustic angiography to the specificity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available. |
| Radiologist Preference (Arbitrary Units) | Baseline | To compare radiologist preference of acoustic angiography (AA) to conventional b-mode ultrasound, for each lesion characteristics which are shape, margins, and vascularity, were examined. Radiologists rated their preferences on a Likert scale from 1 to 5, with 1 strongly preferring conventional ultrasound and 5 strongly preferring AA. Shape, margin, and vascularity values appear to represent mean or median rather than counts. We should select either the mean or the median and provide the standard deviation, which will be 0 if all radiologists assign the same score. |
| Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units) | Baseline | Sensitivity of Acoustic Angiography relative to conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for both modalities. Sensitivity was calculated based on the formula, which is true positive / (true positive + false negative). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated. |
| Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units) | Baseline | Specificity of Acoustic Angiography (AA) and conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for each modality. Specificity was calculated based on the formula, which is true negative / (true negative + false positive). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at a North Carolina cancer center from 04/11/2022 to 08/01/2024, with enrollment occurring between 05/26/2022 and 08/01/2024. The study closed before reaching its target enrollment due to insufficient funding.
Pre-assignment details
Twenty-eight participants consented to the study; one was ineligible and not enrolled. No participants were enrolled in Arm 2 (Thyroid Imaging). Twelve were enrolled in Arm 1 (Breast Imaging), and fifteen in Arm 3 (Healthy Volunteers).
Participants by arm
| Arm | Count |
|---|---|
| Breast Imaging Cohort Women with known breast lesions that are already scheduled to undergo a clinical biopsy. | 12 |
| Thyroid Imaging Cohort Participants with known thyroid lesions that are already scheduled to undergo a clinical biopsy. | 0 |
| Healthy Volunteers Cohort A total of 15 participants will be included to optimize imaging parameters. | 15 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Operational reasons | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Breast Imaging Cohort | Total | Healthy Volunteers Cohort | Thyroid Imaging Cohort |
|---|---|---|---|---|
| Age, Continuous | 52.83 years STANDARD_DEVIATION 18.35 | 41.17 years STANDARD_DEVIATION 18.16 | 29.73 years STANDARD_DEVIATION 12.57 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 26 Participants | 15 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 22 Participants | 14 Participants | 0 Participants |
| Region of Enrollment United States | 12 participants | 27 participants | 15 participants | — |
| Sex: Female, Male Female | 12 Participants | 27 Participants | 15 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 0 | 0 / 15 |
| other Total, other adverse events | 0 / 12 | 0 / 0 | 1 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 0 | 0 / 15 |
Outcome results
Primary
Sensitivity of Acoustic Angiography; Breast Imaging
The sensitivity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Sensitivity (%) = True Positives (TP)+False Negatives (FN)True Positives (TP)
Time frame: Baseline
Population: Patients with known breast lesion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Imaging Cohort | Sensitivity of Acoustic Angiography; Breast Imaging | 50 percentage |
Primary
Sensitivity of Acoustic Angiography; Thyroid Imaging (Percent of Positive Scans)
Sensitivity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Time frame: Baseline
Primary
Specificity of Acoustic Angiography; Breast Imaging (Percent of Negative Scans)
Specificity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Specificity was calculated based on the formula, which is true negative / (true negative + false positive).
Time frame: Baseline
Population: Patient with known breast lesion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Imaging Cohort | Specificity of Acoustic Angiography; Breast Imaging (Percent of Negative Scans) | 67 percentage of benign lesion |
Primary
Specificity of Acoustic Angiography; Thyroid Imaging (Percent of Negative Scans)
Specificity of Acoustic Angiography in the analysis of known thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Time frame: Baseline
Secondary
Area Under the Curve of Acoustic Angiography (Arbitrary Units)
To compare the area under the curve (AUC) of acoustic angiography to the AUC of the B-mode ultrasound. Readers assigned a malignancy likelihood score from 1 to 5, with 1 likely benign to 5 likely malignant. An AUC was then calculated based on these scores. The Receiver operating curve (ROC ) was then plotted from this curve, and the AUC was estimated from the ROC curve.
Time frame: Baseline
Population: Patient with a known breast lesion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Imaging Cohort | Area Under the Curve of Acoustic Angiography (Arbitrary Units) | 50 percentage of probability |
Secondary
Radiologist Preference (Arbitrary Units)
To compare radiologist preference of acoustic angiography (AA) to conventional b-mode ultrasound, for each lesion characteristics which are shape, margins, and vascularity, were examined. Radiologists rated their preferences on a Likert scale from 1 to 5, with 1 strongly preferring conventional ultrasound and 5 strongly preferring AA. Shape, margin, and vascularity values appear to represent mean or median rather than counts. We should select either the mean or the median and provide the standard deviation, which will be 0 if all radiologists assign the same score.
Time frame: Baseline
Population: Patients with a known breast lesion.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Breast Imaging Cohort | Radiologist Preference (Arbitrary Units) | shape | 1 score on a scale | Standard Deviation 0 |
| Breast Imaging Cohort | Radiologist Preference (Arbitrary Units) | margin | 1 score on a scale | Standard Deviation 0 |
| Breast Imaging Cohort | Radiologist Preference (Arbitrary Units) | vascularity | 5 score on a scale | Standard Deviation 0 |
Secondary
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Sensitivity of Acoustic Angiography relative to conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for both modalities. Sensitivity was calculated based on the formula, which is true positive / (true positive + false negative). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated.
Time frame: Baseline
Population: Patients with malignant breast lesion(s).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Imaging Cohort | Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units) | 1.2 ratio |
Secondary
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
To compare (using a reader study) the sensitivity of acoustic angiography to the sensitivity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Time frame: Baseline
Secondary
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Specificity of Acoustic Angiography (AA) and conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for each modality. Specificity was calculated based on the formula, which is true negative / (true negative + false positive). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated.
Time frame: Baseline
Population: Patients with known breast lesion(s).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Imaging Cohort | Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units) | 0.86 ratio |
Secondary
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
To compare (using a reader study) the specificity of acoustic angiography to the specificity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Time frame: Calculated once all imaging is complete [Anticipated 1.5 years]