Radiotherapy-induced cardiotoxicity in breast cancer patients: New approaches of early detection and prediction based on cardiac imaging and circulating biomarkers (European MEDIRAD EARLY-HEART study)

V Walker,S Jacob,A Crijns,J Langendijk,D Spoor,R Vliegenthart,S Combs,M Mayinger,K Borm,A Eraso,F Guedea,M Fiuza,S Constantino Rosa Santos,R Tamarat,D Laurier,J Ferrières,E Cardis,E Mousseaux

doi:10.1016/j.acvdsp.2018.10.275

Abstract

Radiotherapy (RT) plays a major role in breast cancer treatment. However, RT has been linked to long-term cardiac diseases. Therefore, detecting early signs of cardiotoxicity and determining the relationship between radiation dose to specific cardiac structures and subclinical cardiac changes is crucial for primary/secondary prevention. The 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 breast cancer RT and to develop risk models integrating these biomarkers combined with precise dosimetry of cardiac structures. EARLY HEART is a multicenter prospective cohort study that will include 250 unilateral breast cancer women aged 40 to 75 years treated with RT without chemotherapy and followed for 2 years. Baseline (before RT) and follow-up data (at the end of RT, RT + 6, RT + 24 months) include cardiac imaging measurements and circulating biomarkers. Myocardial deformation is evaluated with myocardial strain imaging (2D-speckle-tracking echocardiography). Cardiac magnetic resonance imaging is performed to detect subtle changes in cardiac function and structure. Cardiac computed tomography is performed to evaluate coronary artery lesions. Patients’ RT radiation dose is evaluated for the following cardiac structures: whole heart, left and right atrium, left and right ventricles, strain segments of the left ventricle and coronary arteries. Dose-response relationship will allow modeling radiation-induced occurrence and evolution of subclinical cardiac lesions and biomarkers in order to develop early cardiotoxicity prediction models. Five European centers are currently recruiting patients and end of follow-up is foreseen for 2020. Based on emerging research in advanced imaging modalities and biomarkers, this study will allow enhanced detection and prediction of early cardiotoxicity and patients’ care.

Highlights

Breast cancer (BC) RT can lead to incidental irradiation of the heart, resulting in an increased risk for a variety of heart diseases arising many years after radiotherapy
Identifying BC patients at the highest risk for radiation-induced cardiac complications is crucial for developing strategiesfor primary and secondary prevention, which may contribute to healthy aging
The patients are followed for 2 years after RT, based on cardiac imaging and circulating biomarkers (Blood sample [BLOOD])

Summary

Introduction

Breast cancer (BC) is the most common cancer among w omen, and radiotherapy (RT) plays a major role in its treatment. BC RT can lead to incidental irradiation of the heart, resulting in an increased risk for a variety of heart diseases arising many years after radiotherapy. Identifying BC patients at the highest risk for radiation-induced cardiac complications is crucial for developing strategiesfor primary and secondary prevention, which may contribute to healthy aging. There is still a need for precise knowledge on the relationship betw een radiation dose to specific cardiac sub-structures and early subclinical cardiac changes and their occurrence over time that could lead to cardiac complications

Methods

Discussion

Conclusion