Radiation-Induced Acute Cardiotoxicity in Women with Left Sided Breast Cancer: Results from a Phase II Prospective Clinical Trial

Abstract

<h3>Purpose/Objective(s)</h3> Women with left sided breast cancer (BC) who receive adjuvant radiotherapy (RT) have increased risk of subsequent cardiac events, which may be mitigated by maintaining mean heart dose (MHD) below a threshold of 3 Gy. We hypothesized that early MRI evaluation of cardiac functional changes can identify acute cardiac insult and predict for the risk of long-term cardiac complications. Here we report the findings of a phase II prospective clinical trial evaluating RT-related LV structure and function using cardiac MRI in women with left sided BC treated with adjuvant RT. <h3>Materials/Methods</h3> Patients with left sided BC were enrolled into a single institutional phase II study. After informed consent, patients were allocated for breast RT with free breathing (FB) or with deep inspiratory breath hold (DIBH) delivery, if the predicted MHD was ≤3 Gy (≤ 5 Gy, if also regional nodal RT) or > 3 Gy (> 5 Gy, if regional nodal RT), respectively, on initial FB planning. Cardiac MRI was performed at baseline (pre-RT), and at 16 and 52 weeks. Cardiac toxicity was defined as change in the indexed LV end diastolic volume (LVEDVi), LV ejection fraction (LVEF), indexed LV end systolic volume (LVESVi) and indexed LV mass (LV MASSi). Estimation of multiple serum cardiac biomarkers were also done at the three time points. Continuous variables were expressed as mean ± standard deviation, and ANOVA analysis was used to identify correlation between changes in cardiac parameters from baseline to 16 and 52 weeks, when compared to cardiac radiation dosimetric data. <h3>Results</h3> Of the 69 participants, 25 received RT with FB technique. 44 received RT with DIBH, of which 23 also had received adjuvant chemotherapy (CT) prior to RT. For the FB, DIBH (no CT), and DIBH (with CT) cohorts, MHD was 1.70 ± 0.93 Gy, 1.93 ± 1.30 Gy, and 2.26 ± 1.15 Gy and mean LV dose was 2.47 ± 1.48 Gy, 3.18 ± 1.93 Gy, and 3.23 ± 1.82 Gy, respectively. Evaluation of LVEDVi, LVEF, LVESVi, and LV MASSi showed no statistical difference between the 3 treatment arms. No statistical correlation was noted between LVEF changes (≥ 5% and ≥ 10% from baseline) and the cardiac dosimetric data; all p values > 0.1. Prior CT did not measurably impact cardiac function. <h3>Conclusion</h3> In this prospective study, no significant post-RT cardiac events were demonstrable by functional imaging. This supports the significance of maintaining MHD ≤ 3 Gy to minimize or prevent RT related cardiac toxicity in women with left sided BC. Our observation warrants further investigation in a large prospective setting to evaluate late cardiac events. Analysis of serum cardiac biomarkers is currently ongoing.