ARFI, VisR and DDAI Ultrasound for Improving Discrimination of Malignant and Unresponsive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

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.
    

Detailed 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.
    

Intervention name(s): Ultrasound
Intervention type(s): Device
Intervention description(s): Breast ultrasound
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Keywords: Screening