Assessment of Early Radiation-Induced Changes in Left Ventricular Function by Myocardial Strain Imaging After Breast Radiation Therapy

Abstract

Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall±regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. The MHD was 1.8±1.5Gy for patients receiving left-sided RT (n=26) and 1.1±1.3Gy for patients receiving right-sided RT (n=21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49days (27, 77) before and 54days (25, 78) and 195days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61%±7% vs 59%±8%; P=.003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.