Clinical trial NCT06878547: VisR Ultrasound for Noninvasively Interrogating Stromal Collagen Organization in Women as a Breast Cancer Biomarker: Evaluation of Anisotropy in Cancer Patients
Official title: VisR Ultrasound for Noninvasively Interrogating Stromal Collagen Organization in Women as a Breast Cancer Biomarker: Evaluation of Anisotropy in Cancer Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Keywords: Breast cancer
Ultrasound screening
Ultrasound elastography
ARFI Ultrasound
VisR Ultrasound
Breast cancer diagnosis
Malignant breast lesion
Benign breast lesion
Neoadjuvant chemotherapy
Non-invasive imaging
Tissue anisotropy
Elasticity
Viscosity
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2025-03-17
Enrollment: 250
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Potential study participants will be patients 20-90 years of age. In the first study arm, patients with suspicious breast lesions that are rated 4 (suspicious)or 5 (highly suggestive of malignancy) on the BI-RADS scale will be recruited. In the second study arm, patients with confirmed malignant breast lesion (s) (BI-RADS 6) who are to undergo neoadjuvant systemic therapy will be recruited. All patients will be recruited from and imaged at the University of North Carolina Hospitals. Based on local demographics, we estimate that roughly 20% will be racial and ethnic minorities. Children will not be included in this study. There will be no randomization to study arms and no intervention beyond ARFI, VisR, and DDAI ultrasound imaging.

Brief summary: Purpose: This study will evaluate how measurements of tissue stiffness, viscosity, and anisotropy using non-invasive ultrasound imaging correlate with breast tumor malignancy and response to chemotherapy.

Participants: Up to 200 women with benign or malignant breast tumors for arm 1 and up to 50 women undergoing neoadjuvant chemotherapy in the breast for arm 2 will be recruited.

Procedures (methods): The research team will use an ultrasound scanner to acquire non-invasive elastography data from the breast of each subject, testing a range of transducer rotation angles. Transducer position will be monitored using a position sensor during imaging.

Detailed description: The purpose of the proposed research is to evaluate in vivo the feasibility of ultrasound-derived metrics for stiffness, elasticity, viscosity, and anisotropy for clinical diagnostic breast imaging. 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. This proposed pilot study has two unblinded arms, corresponding to two aims from our NIH R01 grant.

The hypothesis of this study is that ultrasound-derived stiffness, elasticity, viscosity, and anisotropy measured in breast tissue will differ between patients with malignant and benign lesions, and between patients who are responsive versus non-responsive to neoadjuvant systemic therapy (NAT). To test these hypotheses, the research team will pursue the following specific aims from the R01 grant (specific aim #1 is being addressed by a different ongoing study, IRB #24-0122):

Aim #2: Correlate in vivo VisR outcomes to collagen fiber organization in malignant and benign breast masses and surrounding stroma in women, and demonstrate the clinical relevance of such to cancer diagnosis and staging. ARFI, VisR, and DDAI imaging will be performed on women with malignant or benign breast tumors to determine their diagnostic value in predicting malignancy. Results will be compared with histological assessment of collagen fiber organization.

Aim #3: Correlate in vivo VisR outcomes to pre- and post-NAT collagen fiber organization, and demonstrate the clinical relevance of such to predicting pathologic complete response (pCR) to NAT in women. ARFI, VisR, and DDAI imaging will be performed on women with malignant breast tumors undergoing neoadjuvant systemic therapy to monitor changes in mechanical properties during treatment and predict response to chemotherapy from early timepoints. Results will be compared with histological assessment of collagen fiber organization.

Eligibility criteria: Inclusion Criteria (Arm 1):

* Subjects are 20-90 years of age
* Subjects are female
* Breast lesion is sonographically visible with B-Mode ultrasound on diagnostic workup
* Breast lesion(s) have BI-RADS 4a, 4b, 4c, or 5 rating

Exclusion Criteria (Arm 1):

* Inability to provide informed consent
* Inability to communicate in English
* Inability to remain motionless for 15 minutes
* Subjects with breast implants
* Breast mass is deeper than 4 cm from skin surface
* Subjects who are pregnant or lactating
* Subjects who have pacemakers or implanted cardioverters
* Subjects with a history of mastectomy
* Previous biopsy or surgery to the site of the mass, surgical excision of mass of interest
* Subject is male

Inclusion Criteria (Arm 2):

* Subjects are 20-90 years of age
* Subjects are female
* Breast lesion is sonographically visible with B-Mode ultrasound on diagnostic workup
* Breast lesion(s) have BI-RADS 6 rating, subject will be undergoing NAT for stage 2 or 3 malignant breast lesion(s)

Exclusion Criteria (Arm 2):

* Inability to provide informed consent
* Inability to communicate in English
* Inability to remain motionless for 15 minutes
* Subjects with breast implants
* Breast mass is deeper than 4 cm from skin surface
* Subjects who are pregnant or lactating
* Subjects who have pacemakers or implanted cardioverters
* Subjects with a history of mastectomy
* Previous biopsy or surgery to the site of the mass, surgical excision of mass of interest
* Subject is male

Primary outcomes:
measure: ARFI Peak Displacement (PD) in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR Relative Elasticity (RE) in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR Relative Viscosity (RV) in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: ARFI PD DoA in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: ARFI PD DoA in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR RE DoA in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR RE DoA in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR RV DoA in lesion (Study Arm 1)
timeFrame: Baseline imaging
measure: VisR RV DoA in surrounding tissue (Study Arm 1)
timeFrame: Baseline imaging
measure: ARFI Peak Displacement (PD) in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR Relative Elasticity (RE) in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR Relative Viscosity (RV) in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: ARFI PD DoA in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: ARFI PD DoA in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR RE DoA in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR RE DoA in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR RV DoA in lesion (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
measure: VisR RV DoA in surrounding tissue (Study Arm 2)
timeFrame: From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: Lampe Joint Department of Biomedical Engineering
name: Caterina Gallippi, PhD
role: PRINCIPAL_INVESTIGATOR
References: