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

Abstract

BackgroundBreast 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.ObjectiveThe 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.MethodsThe 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.ResultsThis 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.ConclusionsThe 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 RegistrationClinicalTrials.gov NCT03297346; https://clinicaltrials.gov/ct2/show/NCT03297346 (Archived by WebCite at http://www.webcitation.org/72KS7MIUU)Registered Report IdentifierRR1-10.2196/9906

Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography: association between cardiac exposure and longitudinal strain reduction (BACCARAT study)

“…However, with 79 patients, the size of the population involved a limited statistical power for odds ratios sub-analyses which may partly explain the absence of significant results in multivariate analysis. A large multicenter European study (MEDIRAD EARLY-HEART study) is ongoing and plan to include 250 patients which should provide results without this limitation [38]. Some alternatives to cardiac echocardiography for assessment of early cardiac damage exist, such as myocardial scintigraphy or cardiac magnetic resonance imaging.…”

Cardiac Function After Radiation Therapy for Breast Cancer

“…Moreover, it is important to note that we performed explorative analysis in this study. Therefore prospective data still needs to be collected within studies such as the BACCARAT prospective cohort study or the MEDIRAD EARLY HEART study 8,38 . The results of the current study should therefore be considered as hypothesis generating, and not for making definitive conclusions.…”

Positive association between heart dosimetry parameters and a novel cardiac biomarker, solubleST‐2, in thoracic cancer chest radiation

“…Therefore, a long‐term follow‐up study with a large sample size is warranted. Fortunately, a registered clinical study on early detection of RIHD is under way. Despite these limitations, this study analyzed the relationship between cardiac dose parameters and ST change rate for the first time in patients with chest radiation exposure and confirmed a linear relationship between them.…”