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

NCT ID: NCT02496260

Last Updated: 2022-03-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-12-31

Brief Summary

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. This study aims to develop imaging and blood biomarkers of cardiac exposure, as a first step to identifying patients at increased risk for cardiac effects, so they can 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.

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.

Conditions

Breast Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

Research Cardiac MRI

Cardiac MRI has increased use 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. 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 physician. Treatment will not be altered based on MRI.

Intervention Type: PROCEDURE

Biomarkers

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 physician. Treatment will not be altered based upon the data collected from these samples.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients who will receive RT for left-sided breast cancer and can have a contrast-enhanced MRI are eligible.

Exclusion Criteria

• Patients who have a contraindication to contrast-enhanced MRI are not eligible.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: collaborator

Henry Ford Health System

OTHER

Sponsor Role: lead

Responsible Party

Dr. Eleanor Walker

Senior Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Henry Ford Health System

Detroit, Michigan, United States

Countries

United States

References

Morris ED, Ghanem AI, Pantelic MV, Walker EM, Han X, Glide-Hurst CK. Cardiac Substructure Segmentation and Dosimetry Using a Novel Hybrid Magnetic Resonance and Computed Tomography Cardiac Atlas. Int J Radiat Oncol Biol Phys. 2019 Mar 15;103(4):985-993. doi: 10.1016/j.ijrobp.2018.11.025. Epub 2018 Nov 22.

Reference Type: BACKGROUND

PMID: 30468849 (View on PubMed)

Other Identifiers

9481

Identifier Type: -

Identifier Source: org_study_id