Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART Study)

Valentin Walker, Anne Crijns, Johannes Langendijk, Daan Spoor, Rozemarijn Vliegenthart, Stephanie E Combs, Michael Mayinger, Arantxa Eraso, Ferran Guedea, Manuela Fiuza, Susana Constantino, Radia Tamarat, Dominique Laurier, Jean Ferrières, Elie Mousseaux, Elisabeth Cardis, Sophie Jacob, Valentin Walker, Anne Crijns, Johannes Langendijk, Daan Spoor, Rozemarijn Vliegenthart, Stephanie E Combs, Michael Mayinger, Arantxa Eraso, Ferran Guedea, Manuela Fiuza, Susana Constantino, Radia Tamarat, Dominique Laurier, Jean Ferrières, Elie Mousseaux, Elisabeth Cardis, Sophie Jacob

Abstract

Background: Breast cancer is the most common cancer among women, and radiotherapy plays a major role in its treatment. However, breast cancer radiotherapy can lead to incidental irradiation of the heart, resulting in an increased risk for a variety of heart diseases arising many years after radiotherapy. Therefore, identifying breast cancer patients at the highest risk for radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention, which may contribute to healthy aging. There is still a need for precise knowledge on the relationship between radiation dose to specific cardiac structures and early subclinical cardiac changes and their occurrence over time that could finally lead to cardiac complications.

Objective: The MEDIRAD EARLY HEART study aims to identify and validate new cardiac imaging and circulating biomarkers of radiation-induced cardiovascular changes arising within first 2 years of breast cancer radiotherapy and to develop risk models integrating these biomarkers combined with precise dose metrics of cardiac structures based on three-dimensional dosimetry.

Methods: The EARLY HEART study is a multicenter, prospective cohort study in which 250 women treated for breast cancer and followed for 2 years after radiotherapy will be included. Women treated with radiotherapy without chemotherapy for a unilateral breast cancer and aged 40-75 years meet the inclusion criteria. Baseline and follow-up data include cardiac measurements based on two-dimensional speckle-tracking echocardiography, computed tomography coronary angiography, cardiac magnetic resonance imaging, and a wide panel of circulating biomarkers of cardiac injury. The absorbed dose will be evaluated globally for the heart and different substructures. Furthermore, the dose-response relationship will allow modeling the radiation-induced occurrence and evolution of subclinical cardiac lesions and biomarkers to develop prediction models.

Results: This study details the protocol of the MEDIRAD EARLY HEART study and presents the main limits and advantages of this international project. The inclusion of patients began in 2017. Preliminary results are expected to be published in 2019, and complete analysis should be published in 2021.

Conclusions: The MEDIRAD EARLY HEART study will allow identifying the main cardiac imaging and blood-based determinants of radiation-induced cardiac injuries to better propose primary and secondary preventive measures in order to contribute to enhanced patient care and quality of life.

Trial registration: ClinicalTrials.gov NCT03297346; https://ichgcp.net/clinical-trials-registry/NCT03297346 (Archived by WebCite at http://www.webcitation.org/72KS7MIUU).

Registered report identifier: RR1-10.2196/9906.

Keywords: biomarkers; breast cancer; cardiac diagnostic imaging; cardiotoxicity; radiation dosimetry; radiotherapy.

Conflict of interest statement

Conflicts of Interest: None declared.

©Valentin Walker, Anne Crijns, Johannes Langendijk, Daan Spoor, Rozemarijn Vliegenthart, Stephanie E Combs, Michael Mayinger, Arantxa Eraso, Ferran Guedea, Manuela Fiuza, Susana Constantino, Radia Tamarat, Dominique Laurier, Jean Ferrières, Elie Mousseaux, Elisabeth Cardis, Sophie Jacob. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.10.2018.

Figures

Figure 1
Figure 1
Main steps of the EARLY HEART study protocol. RT: radiotherapy; BC: breast cancer; BLOOD: blood sample for circulating biomarkers; ECHO-ST: two-dimensional speckle-tracking echocardiography; CTCA: computed tomography coronary angiography; MRI: magnetic resonance imaging.
Figure 2
Figure 2
Classification of the 17 segments of the left ventricle in bull’s-eye view, echocardiographic parasternal short-axis slices, and apical 4- and 2-chamber views.
Figure 3
Figure 3
The 15 segments of the coronary arteries. LM: left main coronary; LAD: left anterior descending artery; LCX: left circumflex artery; RCA: right coronary artery.

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