br Funding br This study was supported
This study was supported by Beijing Natural Science Foundation (7184240).
Declaration of Competing Interest
The authors are grateful to Mrs. Xuan Zhang and Prof. Zhiyi Pan for providing help in data analysis.
 M. Laplante, D.M. Sabatini, mTOR signaling in growth control and disease, Cell 149
Cardiac Function After Radiation Therapy for Breast Cancer
Veerle A.B. van den Bogaard, MD,* Peter van Luijk, PhD,* Yoran M. Hummel, PhD,y Peter van der Meer, MD, PhD,y Ewoud Schuit, PhD,z Liselotte M. Boerman, MD,x
Departments of *Radiation Oncology and yCardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; zJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Departments of xGeneral Practice, kMedical Oncology, and Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; and #Department of Radiation Oncology, Radiotherapy Institute Friesland, Leeuwarden, the Netherlands
The relationship between in-dividual cardiac dose distri-butions and systolic and diastolic dysfunction is un-clear. We conducted a cross-sectional study consisting of 109 breast cancer survivors treated with postoperative radiation therapy (RT). The
Purpose: The main purpose of this study was to test the hypothesis that incidental car-diac irradiation is associated with changes in cardiac function in breast cancer (BC) survivors treated with radiation therapy (RT).
Methods and Materials: We conducted a cross-sectional study consisting of 109 BC survivors treated with RT between 2005 and 2011. The endpoint was cardiac function, assessed by echocardiography. Systolic function was assessed with the left ventricular ejection fraction (LVEF) (n Z 107) and the global longitudinal strain (GLS) of the left ventricle (LV) (n Z 52). LV diastolic dysfunction (n Z 109) was defined by e’ at the lateral and septal region, which represents the relaxation velocity of the myocardium. The individual calculated RT dose parameters of the LV and coronary BYL-719 were collected from 3-dimensional
Conflict of interest: J.A.L. reports an honorarium for consultancy paid to UMCG Research BV by IBA, a research collaboration agreement with
IBA, a research collaboration agreement with Philips, a research collab-oration agreement with Mirada, and a research and development collab-oration agreement with RaySearch, outside the submitted work.
Supplementary material for this article can be found at https://doi.org/
Volume 104 Number 2 2019 Cardiac function after breast irradiation 393
endpoint was systolic and diastolic cardiac function, assessed by echocardiogra-phy. Although no relation between RT dose parameters and left ventricle ejection fraction was found, an asso-ciation between individual RT dose and global longitu-dinal systolic strain of the left ventricle was determined.
computed tomographyebased planning data. Univariable and multivariable anal-ysis using forward selection was performed to identify the best predictors of car-diac function. Robustness of selection was assessed using bootstrapping. The resulting multivariable linear regression model was presented for the endpoints of systolic and diastolic function.
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.
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 heart 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.