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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02494453
• Other study ID #: UMCC 2014.151
• Status: Completed
• Start date: June 2015
• Est. completion date: July 2017

Study information

• Verified date: July 2019
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Procedure:
• Research Cardiac MRI
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.
• Biomarkers
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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number patients in which blood and serum biomarkers were identified that correlated with cardiac damage due to radiation	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.	One year
Secondary	Number of unique biomarkers identified that were associated with radiation related cardiac injury	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.	One year