Performance of Contrast-Enhanced Spectral Mammography to Assess Neoadjuvant Chemotherapy Response (CEDM)

This study is designed to investigate the diagnostic accuracy of Contrast Enhanced Spectral Mammography (CEDM) in predicting early neoadjuvant therapy response and pathologic complete response (pCR) compared to mammography.

Patients diagnosed with invasive breast cancer with available mammography and ultrasound imaging are eligible for the study.

Eligible patients will be imaged at baseline (before initiation of neoadjuvant chemotherapy or endocrine therapy), early (2-4 cycles of neoadjuvant therapy) and late (after completion of neoadjuvant chemotherapy or endocrine therapy) timepoints with mammography. CEDM will be done within 2 weeks of the specified timepoint. Additionally, a survey of subject experience with CEDM and other pre-operative imaging will be collected after CEDM is performed.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Digital Mammography; Drug: Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml

Detailed Description

The use of neoadjuvant systemic therapy in the treatment of breast cancer patients is increasing beyond the scope of locally advanced disease. Imaging provides important information in assessing response to therapy as a complement to conventional tumor measurements via physical examination. Tumor response to neoadjuvant therapy can also provide prognostic information. The attainment of pCR after completion of neoadjuvant therapy and surgical resection is associated with improved disease-free survival. This correlation is especially strong for Triple-receptor negative and human epidermal growth factor receptor 2 (HER-2) positive breast cancer. Studies of neoadjuvant therapy have used a variety of methods for assessing tumor response. Currently, there are no established clinical practice guidelines for how best to assess tumor response to neoadjuvant therapy. Typically, patients undergo conventional breast imaging such as mammography and ultrasonography (US) and physical examination, and dynamic contrast-enhanced breast magnetic resonance imaging (DCR-MRI) in selected cases.

Contrast Enhanced Digital Mammography (CEDM) is a novel imaging technique, which allows digital mammography to be used with contrast enhancement to depict cancers that would otherwise be occult on standard unenhanced mammography. CEDM is performed with and without intravenous iodine contrast, using the dual energy subtraction technique. Compared with mammography and US, CEDM improves the sensitivity for breast cancer detection without decreasing specificity. CEDM digital detector has higher spatial resolution than MRI, revealing details that are approximately 10 times better. In contrast to the rapid washout in MRI, enhancement on CEDM in fact persists for at least 10 min after contrast agent infusion. Today CEDM is available commercially for clinical use. It is estimated that over 200,000 CEDM examinations have been performed to date in both research and clinical settings. CEDM costs significantly less compared to MRI. Furthermore, longer time delays between contrast injection and CEDM exposure could result in stronger enhancement and hence better visibility compared to MRI, especially given the much higher spatial resolution of digital mammography. It is unknown whether CEDM can improve the sensitivity of mammography in the early assessment of neoadjuvant therapy response. We hypothesize that CEDM is superior to mammography and ultrasound in assessing early response, and pre-surgical residual cancer after neoadjuvant therapy, and when performed, non-inferior to MRI in assessing the residual disease using the metrics of pCR and residual cancer burden (RCB).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ipsilateral intact biopsy-proven breast cancer clinical stage T1-T4 (by imaging)
• Available mammography and ultrasound imaging of the existing index cancer, with orthogonal measurements
• Prior history of ipsilateral or contralateral breast cancer, presenting with a new primary or recurrent disease
• Patients who were determined to be candidates for either neoadjuvant chemotherapy or neoadjuvant endocrine therapy by the treating physician
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for days following completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

• History of ipsilateral mastectomy
• Women who already started neoadjuvant chemotherapy or endocrine therapy
• Woman who may be pregnant or nursing an infant
• Prior history of anaphylactic or anaphylactoid reaction to any contrast.
• Prior allergy to iodine or iodinated contrast.
• Impaired renal function measured by estimated glomerular filtration rate (eGFR) < 60 milliliters per minute.
• Patients with known distant metastasis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Breast cancer patients; Patients with ipsilateral intact biopsy-proven breast cancer	Procedure: Digital Mammography; Digital Mammography enhanced with an iodinated contrast agent; Drug: Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml; Injection of low osmolar contrast material during the digital mammography exam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of Predicting pCR (Pathologic Complete Response) for CEDM	Sensitivities in predicting pCR will be calculated for CEDM and measured as AUC	4 to 6 months from initiation of neoadjuvant therapy until final surgery
Sensitivity of Predicting pCR (Pathologic Complete Response) for Mammography	Sensitivities in predicting pCR will be calculated for mammography measured as AUC	4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of Predicting pCR (Pathologic Complete Response) for CEDM	Specificity of predicting pCR will be calculated for CEDM and measured as AUC	4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of Predicting pCR (Pathologic Complete Response) for Mammography	Specificity of predicting pCR will be calculated for mammography and measured as AUC	4 to 6 months from initiation of neoadjuvant therapy until final surgery
Diagnostic Accuracy of Contrast-enhanced Mammography in Assessing pCR or Non Response	ROC analysis will be used to assess the diagnostic performance of CEDM. The Area under the receiver operating characteristic (ROC) curve (AUC) will be compared. A leave-one-out cross validation algorithm will be used to reduce bias from overfitting.	4 to 6 months from initiation of neoadjuvant therapy until final surgery
Correlation of Residual Tumor Size With Pathologic Size	Spearman's rank correlation will be used to measure the association between final pathologic and imaging tumor size	4 to 6 months from initiation of neoadjuvant therapy until final surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify any patient preference differences between CEDM and breast MRI	A survey will be administered to each patient who undergo both breast MRI and contrast enhanced mammography to assess their preference.	Up to 4 years

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Basak Dogan, MD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: mammography; contrast enhanced spectral mammography
• Other Study ID Numbers: STU-2019-0529

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes