Pilot Study of Biomarkers and Cardiac MRI as Early Indicators of Cardiac Exposure Following Breast Radiotherapy

NCT02494453 | Completed DMC

• 1 other identifier: UMCC 2014.151
• Study Type: observational
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with breast cancer receive low doses to smaller volumes of the heart, but they also have an excellent long-term survival, so it is crucial to study the effects of low dose radiotherapy. Indeed, a recent study suggests that these effects can be seen within the first 5 years after treatment, and that there is no dose threshold. The investigators wish to develop imaging and blood biomarkers of cardiac exposure, as a first step to identifying patients at increased risk for cardiac effects. These patients can then be targeted for close monitoring and early intervention, potentially with statins or ACE inhibitors. Additionally, by characterizing a time-course and radiation dose-volume relationship, potentially real-time modifications can be made to radiotherapy (RT) field design for patients sensitive to RT effects. Finally, this information can be incorporated into better designs of treatment plans for future patients.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients in which cardiac MRI indicated subclinical cardiac abnormalities after radiotherapy that correlated with cardiac events

  The study aims to characterize longitudinal changes in imaging characteristics of cardiac damage. Cardiac MRI endpoints will include myocardial edema, microvascular dysfunction, myocardial fibrosis, and subclinical impairment of systolic and diastolic function.

  One year

Secondary Outcomes (2)

• Number patients in which blood and serum biomarkers were identified that correlated with cardiac damage due to radiation

  One year

• Number of unique biomarkers identified that were associated with radiation related cardiac injury

  One year

Study Arms (1)

Cardiac MRI

Procedure: Research Cardiac MRI; Procedure: Biomarkers

Interventions

Research Cardiac MRI PROCEDURE

Cardiac MRI has increasing utility in evaluating structural and functional cardiac pathologies. For detection of coronary artery disease, MRI outperforms SPECT and dobutamine stress echocardiography for the detection of ischemia. MRI also can detect wall-motion abnormalities and other dysfunction. Dynamic contrast-enhanced MRI (DCE-MRI) can evaluate microvascular parameters such as vessel permeability and fluid volume fraction as an assessment of tissue perfusion. Thus, cardiac MRI holds promise for early detection of subclinical cardiac abnormalities after radiotherapy and could potentially identify patients for intervention to prevent cardiac events. All patients will follow the protocol calendar requiring research MRIs, but will receive standard radiation treatment determined by their treating physician. In this study, treatment will not be altered based on the data collected from these MRIs.

Cardiac MRI

Biomarkers PROCEDURE

Scant data exist on potential biomarkers of cardiac radiation exposure and damage. However, we have identified potential candidates based on other processes affecting heart function in a way similar to probable mechanisms of RT-related injury. For fibrosis and left ventricular dysfunction, these include galectin-3 and N-terminal-Pro brain natriuretic peptide. For myocyte destruction, troponin; for inflammation and oxidative stress, C-reactive protein, myeloperoxidase, and growth differentiation factor 15. Additional blood will be collected and stored for future assessment of other candidate biomarkers. All patients will follow the calendar of protocol required research blood draws for biomarker collection, but will receive standard radiation treatment as clinically indicated by their treating physician. In this study, treatment will not be altered based upon the data collected from these samples.

Cardiac MRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients receiving radiotherapy for treatment of left-sided breast cancer.

You may qualify if:

• Patients who will receive radiotherapy as treatment for left-sided breast cancer
• Patients must understand and be willing to sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks.

You may not qualify if:

• Patients with a contraindication to contrast-enhanced MRI

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Scant data exist on potential biomarkers of cardiac radiation exposure and damage. However, the investigators have identified potential candidates based on other processes affecting heart function in a way similar to probable mechanisms of RT-related injury. For fibrosis and left ventricular dysfunction, these include galectin-3 and N- terminal-Pro brain natriuretic peptide. For myocyte destruction, troponin; for inflammation and oxidative stress, C-reactive protein, myeloperoxidase, and growth differentiation factor 15. Additional blood will be collected and stored for future assessment of other candidate biomarkers.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Biomarkers

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biological Factors

Study Officials

• Corey Speers, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: July 10, 2015
• Study Start: June 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: July 30, 2019

Record last verified: 2019-07

Locations

US (1)