br Results The median time

Results: The median time between BC diagnosis and echocardiography was
7 years. No relation between RT dose parameters and LVEF was found. In the multivariable analysis for the endpoint GLS of the LV, the maximum dose to the left main coronary artery was most often selected across bootstrap sam-ples. For decreased diastolic function, the most often selected model across boot-strap samples included age at time of BC diagnosis and hypertension at baseline. Cardiac dose-volume histogram parameters were less frequently selected for this endpoint.
Conclusions: This study shows an association between individual cardiac dose distributions and GLS of the LV after RT for BC. No relation between RT dose parameters and LVEF was found. Diastolic function was most asso-ciated with age and hypertension at time of BC diagnosis. Further research is needed to make definitive conclusions. 2019 Elsevier Inc. All rights reserved.
Introduction
Adjuvant radiation therapy (RT) for breast cancer (BC) has been associated with a wide variety of cardiac dis-eases.1 In relation to BC radiation, risk of ischemic SPDP disease has been well established.2-4 Recent studies have shown significant relationships between RT to the whole heart and left ventricle (LV) and acute coronary events in BC populations.5,6 However, the relationship between thoracic RT and cardiac dysfunc-tion is less clear.
The left ventricular ejection fraction (LVEF) by echo-cardiography is the cornerstone of LV systolic function assessment in clinical practice. However, LVEF can un-derestimate actual cardiac damage because of the compensatory reserve of the myocardium that enables adequate ventricular outcome even in the presence of dysfunctional myocytes.7 Global longitudinal systolic strain (GLS) is an echocardiographic technique that detects and quantifies subclinical and subtle disturbances in LV systolic function and can thus be considered as an early marker for radiation-induced cardiac damage.8 This is particularly relevant because the latency time for symp-tomatic radiation-induced cardiovascular diseases is rela-tively long. These early markers may be helpful to identify patients at risk for major cardiac events who may benefit from preventive strategies.
The aim of this study was to assess the relationship between radiation dose to the LV and radiation dose to the coronary arteries and LV systolic and diastolic function in BC survivors treated with RT based on individual planned 3-dimensional (3D) dose distributions and computed to-mography (CT) information. 
Methods and Materials
Study population
The Department of General Practice of the University Medical Center Groningen (UMCG) performed a cross-sectional, population-based study to assess the frequency of cardiac dysfunction in female BC survivors in a primary care setting.9 Patients were included if they received a diagnosis of BC stage I to III and had no disease activity for at least 5 years after treatment. Information could be extracted from electronic patient records of 1 of 80 participating primary care physi-cians (PCPs) in the northern Netherlands region. Patients were excluded if they had metastatic disease at the time of BC diagnosis, had a history of other malignancies, or received prior chemotherapy or RT treatment of other malignancies. The main study included 350 BC survivors treated from 1988 to 2011. All 350 patients underwent echocardiography. Because of the inclusion criteria of the main study with the date of treatment mostly in the pre-CT era, patients were only selected when CT-based RT treatment planning data were available. Therefore, our total study population was composed of 109 BC survivors treated with RT from 2005 to 2011.