Early detection of cardiovascular changes after radiotherapy for breast cancer: Protocol for a European multicenter prospective cohort (MEDIRAD EARLY HEART Study) (Preprint)

BACKGROUND Breast cancer (BC) is the most common cancer among women and radiotherapy (RT) plays a major role in its treatment. However, BC RT can lead to incidental irradiation of the heart, resulting in an increased risk of a variety of heart diseases arising many years after radiotherapy. Therefore, identifying BC patients with the highest-risk of radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention, which may contribute to healthy ageing. There is still a need of precise knowledge on the relationship between radiation dose to specific cardiac structures and early subclinical cardiac changes and their occurrence in 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 in the first 2 years after BC RT and to develop risk models integrating these biomarkers combined with precise dose metrics of cardiac structures based on 3D-dosimetry. METHODS EARLY HEART study is a multicenter prospective cohort study that will include 250 women treated for breast cancer and followed for 2 years after RT. Women treated with RT without chemotherapy, for a unilateral breast cancer and aged 40 to 75 years meet the inclusion criteria. Baseline and follow-up data include cardiac measurements based on 2D-speckle-tracking-echocardiography, on coronary computed tomography angiography, on cardiac magnetic resonance imaging and a wide panel of circulating biomarkers of cardiac injury. The absorbed dose is evaluated globally for the heart and different substructures. Dose-response relationship will allow modeling radiation-induced occurrence and evolution of subclinical cardiac lesions and biomarkers in order to develop prediction models. RESULTS The article details the protocol of the MEDIRAD EARLY HEART study, and presents main limits and advantages of this international project. 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 patients’ care and quality of life. CLINICALTRIAL Clinicaltrials.gov NCT03297346 - https://clinicaltrials.gov/ct2/show/NCT03297346