Cardiac Effects of Modern Breast Radiation Therapy in Patients Receiving Systemic Cancer Therapy
Eva Berlin, Kyunga Ko, Lin Ma, Ian Messing, Casey Hollawell, Amanda M. Smith, Neil K. Taunk, Vivek Narayan, Jenica Upshaw, Amy S. Clark, Payal D. Shah, Hayley Knollman, Saveri Bhattacharya, Daniel Koropeckyj-Cox, Jessica Wang, Nikhil Yegya‐Raman, Ivy S. Han, Bénédicte Lefebvre, Li Tang, Nicholas S. Wilcox, Wonyoung Jung, Jinbo Chen, Gary M. Freedman, Bonnie Ky
Abstract
BACKGROUND: Radiation therapy (RT) improves breast cancer outcomes, but cardiac morbidity remains a concern. OBJECTIVES: This study sought to evaluate changes in cardiac function after RT and the relationship between cardiac dose metrics and echocardiography-derived measures of function. METHODS: In a longitudinal cohort study of women with breast cancer, radiation cardiac dose metrics and core lab quantitated echocardiographic measures of cardiac function were evaluated. Dose metrics included the whole heart, left ventricle, right ventricle, and left anterior descending artery (LAD). Echocardiographic measures included left ventricular ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e' (ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity), Ea/Es (ventricular arterial coupling; ratio of effective arterial elastance to end systolic elastance), and right ventricular fractional area change. The mean change in echocardiographic measures over time and the association between cardiac dose metrics and echocardiographic measures were estimated by repeated-measures multivariable linear regression via generalized estimating equations. RESULTS: The cohort included 303 participants (median age 52 years, 33.3% African American) who received adjuvant RT (2010-2019) with a median mean heart dose of 1.19 Gy (Q1-Q3: 0.75-2.61 Gy), were followed over a median of 5.1 years (Q1-Q3: 3.2-7.1 years). Across all participants, there was a modest increase in LVEF (52.1% pre-RT to 54.3% at 5 years; P < 0.001) but a worsening in sensitive measures of function, such as circumferential strain (-23.7% pre-RT to -21.0% at 5 years; P = 0.003). Among left-sided/bilateral breast cancer participants, changes in cardiac function were observed across all parameters (P < 0.05). The maximum LAD dose was associated with a modest worsening in LVEF, longitudinal strain, circumferential strain, and E/e'. CONCLUSIONS: Over a median of 5.1 years, modest changes in cardiac function were observed with RT. Maximum LAD dose was associated with a worsening in systolic and diastolic function parameters.