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

Completed

• Conditions: Breast Cancer
• Interventions: Procedure: Research Cardiac MRI; Procedure: Biomarkers

• Registration Number: NCT02494453
• Lead Sponsor: University of Michigan Rogel Cancer Center

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.

Detailed Description

Radiotherapy plays an integral role in breast cancer therapy. Multiple randomized studies have demonstrated decreased local-regional recurrence rates and decreased breast-cancer mortality. However, balanced with this survival benefit is the potential toxicity of the treatment itself. In particular, cardiac effects of radiotherapy have been a concern and an area of research for the past 20 years. From long-term follow up of patients with lymphoma, it is known that radiotherapy can lead to increased risk of myocardial infarction, valvular dysfunction, systolic and diastolic function abnormalities, and heart failure among cancer-survivors. Patients with breast cancer receive lower 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 hypothesize that they can 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 RT field design for patients sensitive to RT effects. Finally, this information can be incorporated into better designs of treatment plans for future patients.

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-24
• Study First Submitted QC: 2015-07-09
• Study First Posted: 2015-07-10
• Primary Completion: 2017-07
• Study Completion: 2017-07
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-26
• Last Update Posted: 2019-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• 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.

Exclusion Criteria

• Patients with a contraindication to contrast-enhanced MRI

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cardiac MRI	Research Cardiac MRI	-
Cardiac MRI	Biomarkers	-

Primary Outcome Measures

Name	Time	Method
Number of patients in which cardiac MRI indicated subclinical cardiac abnormalities after radiotherapy that correlated with cardiac events	One year	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.

Secondary Outcome Measures

Name	Time	Method
Number patients in which blood and serum biomarkers were identified that correlated with cardiac damage due to radiation	One year	The study aims to characterize longitudinal changes in potential early biomarkers of cardiac damage. Biomarker endpoints derived from blood or its components include measuring levels of galectin-3, NT-Pro brain natriuretic peptide, troponin, C-reactive protein, myeloperoxidase, and growth differentiation factor 15.
Number of unique biomarkers identified that were associated with radiation related cardiac injury	One year	Biomarker endpoints derived from blood or its components include measuring levels of galectin-3, NT-Pro brain natriuretic peptide, troponin, C-reactive protein, myeloperoxidase, and growth differentiation factor 15. Additional biomarkers may be included as the research in those fields progresses during the conduct of this clinical trial.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States