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  • br selected multivariable linear regression model was pre

    2020-08-28

    
    selected multivariable linear regression model was pre-sented. This analysis was done for the endpoints LVEF, GLS of the LV, and diastolic function, respectively. Data were analyzed using MATLAB (version R2017a) and SPSS (IBM SPSS Statistics, version 22, IBM Corp).
    Results
    Patient characteristics
    The characteristics of the patients at baseline and at the time of echocardiography are summarized in Table 1. Tumor and treatment characteristics are summarized in Table 2. The median age at diagnosis was 55 years (inter-quartile range [IQR], 49-60), and the median age at time of echocardiography was 62 years (IQR, 56-67). The median follow-up time was 7 years (IQR, 5-8).
    Results of echocardiography
    Systolic function
    The results of echocardiography are summarized in Table 3. Using LVEF <54% as a cutoff value, 15 of 107 BC sur-vivors (14%) had an abnormal LVEF at the time of echocardiography.
    We further analyzed the data by investigating a possible relationship between radiation dose and posttreatment LVEF. Clinical factors (age, diabetes mellitus, hyperten-sion, dyslipidemia, smoking, and number of pack-years), systemic therapy (chemotherapy, endocrine therapy, and trastuzumab), and DVH parameters (mean dose, maximum dose, and mean V[x] in bins of 5 Gy) of the LV and cor-onary SCR 7 were entered in the multivariable analysis before application of forward selection. Results of the variable selection in the 1000 bootstrap samples are shown in Figures E2 and E3 (available online at https://doi.org/10. 1016/j.ijrobp.2019.02.003). No relationships with RT dose parameters or use of systemic therapy were found. In the final model, LVEF was associated with smoking at time of diagnosis (Table E1; available online at https://doi.org/10. 1016/j.ijrobp.2019.02.003).
    Because a decreased LVEF indicates relatively late and severe cardiac damage, we performed an additional analysis using the subclinical parameter GLS of the LV as an endpoint. According to 52 echocardiographies, the mean GLS of the LV was 16.95% (range, 23.26% to 9.44%). The multivariable analysis included the following risk factors before variable selection: clinical factors (age, diabetes mellitus, hypertension, dyslipidemia, smoking, and number of pack-years), systemic therapy variables (chemotherapy, endocrine therapy, and trastuzumab), and DVH parameters (mean dose, maximum dose, and mean V
    [x] in bins of 5 Gy) of the LV and coronary arteries. On the basis of variable selection in the 1000 bootstrap samples, we found that the maximum dose to the LMCA was selected
    396 van den Bogaard et al. International Journal of Radiation Oncology Biology Physics
    Table 1 Patient characteristics at the time of breast cancerdiagnosis and at the time of echocardiography for all 109breast cancer survivors
    At At time of Variable baseline echocardiography
    Age at BC diagnosis, y
    Median
    Median
    7 IQR
    5-8 Cardiovascular risk factors
    Diabetes mellitus, n (%)
    Complaints of heart
    Abbreviations: BC Z breast cancer; BMI Z body mass index; IQR Z interquartile range.
    * As reported by their primary care physician or stated in their
    hospital medical charts.
    y Arrhythmias included supraventricular paroxysmal tachycardia, ventricular paroxysmal tachycardia, and/or atrial fibrillation.
    z Nonrheumatic valve disorder included aortic stenosis and/or mitral valve insufficiency.
    x Ischemic heart diseases included coronary atherosclerosis, myocardial infarction, and unstable/stable angina pectoris.
    most across bootstrap samples (Fig. E4; available online at https://doi.org/10.1016/j.ijrobp.2019.02.003). All DVH parameters that were selected related to dose to the coro-nary arteries, not to the LV. The frequency plot of 
    the selected models is shown in Figure E5 (available online at https://doi.org/10.1016/j.ijrobp.2019.02.003). Model characteristics of the final model for the endpoint GLS of the LV, consisting of the maximum dose to the LMCA, are shown in Table 4.
    Diastolic function
    The multivariable analysis included the same risk factors before variable selection: clinical factors (age, diabetes mellitus, hypertension, dyslipidemia, smoking, and number of pack-years), systemic therapy variables (chemotherapy, endocrine therapy, and trastuzumab), and DVH parameters (mean dose, maximum dose, and mean V[x] in bins of 5 Gy) of the LV and coronary arteries. On the basis of variable selection in the 1000 bootstrap samples, we found that clinical variables were selected most across bootstrap samples (Fig. E6; available online at https://doi.org/10. 1016/j.ijrobp.2019.02.003). Variable age at baseline was selected 1000 times from 1000 bootstrap samples, and hypertension at baseline was selected 629 times. DVH parameters were less frequently selected for this endpoint. The frequency plot of the selected models is shown in Figure E7 (available online at https://doi.org/10.1016/j. ijrobp.2019.02.003). Details of the final model for the endpoint diastolic function, consisting of age at baseline and hypertension, are shown in Table 5.