Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03785782 |
| Other study ID # |
LCCC1745 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 10, 2018 |
| Est. completion date |
July 15, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
UNC Lineberger Comprehensive Cancer Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Purpose: The purpose of this study is to evaluate in vivo the diagnostic relevance of
ultrasound-derived metrics for stiffness, elasticity, viscosity, and anisotropy.
Participants: Forty women with breast lesions that have a BIRADS-4 or BIRADS-5 rating and
forty women undergoing neoadjuvant chemotherapy (NAC) for malignant breast lesions will be
recruited. Subjects will be recruited from the Breast Imaging Division of UNC Hospitals.
Procedures (methods): In this exploratory clinical study, the investigators will attempt to
demonstrate that ARFI, VisR, and DDAI ultrasound reliably detect malignant breast masses (Aim
#1) and distinguish masses that respond to chemotherapy from those that do not (Aim #2). The
ARFI, VisR, and DDAI imaging location will be on the surface of the breast, above the
suspicious or malignant mass. This unblinded, open-label, exploratory study will be conducted
in 40 women with diagnosed BIRADS-4 or -5 masses in Aim #1 and in 40 women with malignant
masses undergoing neoadjuvant chemotherapy (NAC) in Aim #2.
Description:
The primary objective of breast cancer screening is to identify early stage cancer, or
precancerous lesions, at a time before symptoms emerge and when treatment is likely to result
in a cure. Screening is beneficial when it averts progression of disease to metastasis and/or
death, but adverse effects to patients (and unnecessary medical expense) may result
downstream from false positives and indiscrimination of masses that will not respond to
treatment. The sensitivity of digital mammography, the current screening standard in the US,
has been reported in the range of 0.40 to 0.85, with a positive predictive value of 0.31.
Sensitivity is increased by augmenting mammography with MRI and B-Mode ultrasound, but false
positive rates may also increase3. There exists a vital need for a screening technology that
exhibits high sensitivity and specificity for cancer detection with early identification of
unresponsive masses.
This urgent need could be met by exploiting new imaging biomarkers. Specifically, the
mechanical properties of breast tissue have been used for cancer detection, with both
elasticity and viscosity demonstrated for discriminating malignant from benign lesions.
Further, tissue anisotropy has been shown to correlate with core biopsy result and tumor
grade, with large cancers significantly more anisotropic than small cancers. Importantly,
while both MRI and ultrasound can be used to measure these biomarkers, ultrasound's cost
effectiveness and ease of implementation render it an efficient platform to pursue.
The long-term goal of this research program is to develop a new ultrasound-based
breast-screening tool to augment mammography. As a critical first step toward achieving this
goal, the primary objective of the proposed research is to evaluate in vivo the diagnostic
relevance of ultrasound-derived metrics for stiffness, elasticity, viscosity, and anisotropy.
These biomarkers will be measured using novel, noninvasive ultrasound technologies under
development in Dr. Gallippi's laboratory: 1) Acoustic Radiation Force Impulse (ARFI)
ultrasound for interrogating tissue stiffness, 2) Viscoelastic Response (VisR) ultrasound for
assessing tissue elasticity and viscosity, and 3) Dynamic Displacement Anisotropy Imaging
(DDAI) for measuring tissue anisotropy. These technologies have been demonstrated previously
for delineating atherosclerosis, muscular dystrophy, and renal dysfunction.
A.1.2.State the research question(s) (i.e., specific study aims and/or hypotheses).
The investigators hypothesize that ultrasound-derived stiffness, elasticity, viscosity, and
anisotropy will correlate with lesion malignancy and response to treatment. To test this
hypothesis, they will pursue the following specific aims:
Aim #1: Quantify the ability of ultrasound-derived stiffness, elasticity, viscosity, and
anisotropy to detect malignancy. ARFI, VisR, and DDAI imaging will be performed on suspicious
breast lesions in 40 women with BIRADS-4a, 4b, 4c, or -5 ratings. The diagnostic accuracy of
imaging metrics will analyzed, with malignancy confirmed by histology as the outcome.
Aim #2: Quantify the ability of ultrasound-derived stiffness, elasticity, viscosity, and
anisotropy to predict a positive response to treatment. ARFI, VisR, and DDAI imaging will be
performed serially - once every four weeks over the course of neoadjuvant chemotherapy (NAC)
- on malignant breast lesions in 40 women. Changes in outcome metrics over time will be
correlated to overall reduction in tumor size (diameter and area). The ability of ultrasound
metrics to predict a positive response to treatment will be examined. A positive response to
treatment will be determined according to the Response Evaluation Criteria in Solid Tumors
(RECIST) guidelines.
