Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study

Abstract

BackgroundRadiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry.Methods/DesignBACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relationship. Multivariate model of normal tissue complication probability (NTCP) will also be proposed.DiscussionTools and results developed in the BACCARAT study should allow improving prediction and prevention of potential lesions to cardiac normal tissues surrounding tumors and ultimately enhance patients’ care and quality of life.Trial registrationClinicalTrials.gov: NCT02605512

Long‐term cardiovascular mortality after radiotherapy for breast cancer: A systematic review and meta‐analysis

“…Different diagnostic methods—including measurements of functional myocardial dysfunction, including strain and strain rate based on 2D‐speckle tracking echocardiography; anatomical coronary lesions including description of plaques in segments of coronary arteries based on coronary computed tomography angiography; and a wide panel of circulating biomarkers—might be useful options to detect early cardiotoxicity related to RT. Although modern RT has decreased the risk of cardiac mortality, the risk still exists even if mean doses have decreased, and it is important to continue efforts in radiation protection of healthy tissues neighboring RT‐treated organs …”

“…Although modern RT has decreased the risk of cardiac mortality, the risk still exists even if mean doses have decreased, and it is important to continue efforts in radiation protection of healthy tissues neighboring RT-treated organs. 31…”

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

“…While in previous clinical studies, mean heart dose was related to the likelihood of RIHD [12], and the risk of major coronary events in breast cancer patients increased linearly by approximately 4-16% for each 1 Gy in mean heart dose received [6,9,10], other studies have shown that dose to the coronary arteries may also be an indicator of risk of developing coronary artery stenosis, an important aspect of RIHD [73]. Thus, there is a need for irradiation of small segments of the heart in pre-clinical models, which may include key sections of coronary arteries, to accurately predict risk factors and successfully develop interventions in RIHD [64,[74][75][76][77][78]. Partial heart irradiation in small animals may also be used to elucidate ways in which high-dose radiation treatment of segments of the heart can decrease ventricular tachycardia events in patients [79].…”

Treatment planning and evaluation of gated radiotherapy in left-sided breast cancer patients using the CatalystTM/SentinelTM system for deep inspiration breath-hold (DIBH)

“…Recent data suggest, that even lower radiation doses to the heart may play a relevant role for the development of late cardiac toxicity after breast cancer treatment [6–8]. Radiation exposure of the heart can result in coronary artery disease, congestive heart failure, valvular heart disease, pericardial disease, conduction abnormalities and sudden cardiac death [9].…”