Cardiotoxicity in Patients with Ductal Carcinoma In Situ (DCIS) in the Contemporary Radiotherapy Era

Abstract

<h3>Purpose/Objective(s)</h3> Risk of radiation induced cardiotoxicity with modern radiotherapy (RT) for patients with DCIS is unclear. Many studies have observed a higher risk of cardiac toxicity for women treated with left vs right breast RT. However, most analyses were conducted in an older era and included patients with invasive disease, who also have risk of cardiac toxicity from anthracycline, taxane, and/or Herceptin-based systemic therapy and have more limited long-term follow up due to risk of death due to breast cancer. In this study, we evaluated the impact of modern RT on cardiac events in patients with DCIS. Our hypothesis is that toxicity rates will not differ significantly between left and right DCIS patients treated with modern breast RT. <h3>Materials/Methods</h3> We identified patients with DCIS who were treated with breast conserving surgery and RT at our institution between 2006-2017. Patients with bilateral breast RT or prior thoracic RT were excluded. Patients were treated using CT simulation and modern RT techniques including 3D-CRT, brachytherapy, and IMRT. Prone and deep inspiration breath hold (DIBH) delivery were utilized. Patients received either whole breast or partial breast RT. We recorded 5 cardiac event classes: ischemic, valvular, arrhythmia, cardiomyopathy, and pericardial events. Incidence of cardiac events were compared for right vs left DCIS, and stratified by age and risk factors such as previous cardiac disease, BMI, tobacco use, hyperlipidemia, hypertension, and diabetes. Comparisons were done using Fisher's exact test. <h3>Results</h3> 546 patients (262 left and 284 right) met the inclusion criteria for our study. Mean age at diagnosis was 57.8 years and mean follow up was 105 months. Cardiac events occurred at median of 52 months, mean of 59 months, and range of 7-147 months after RT. There was no significant difference in incidence of overall cardiac events among patients with left vs. right DCIS (p>0.05). There was also no significant difference among left vs. right DCIS patients for any event class, including ischemic, valvular, arrhythmia, cardiomyopathy, and pericardial events (p>0.05). Similarly, we did not observe a significant difference in rate of cardiac events for patients with left vs. right DCIS when patients were divided into two groups based on year of RT delivery and when stratified by risk factors for any cardiac outcome. <h3>Conclusion</h3> Incidence of cardiac events after adjuvant breast RT did not differ significantly between left and right DCIS patients, including overall risk as well as risk of each cardiac event class (ischemic, valvular, arrhythmia, cardiomyopathy, and pericardial). This suggests that modern radiotherapy techniques such as partial breast RT or whole breast RT using 3D-CRT, prone, or DIBH techniques, with CT simulation based planning and strict cardiac dose-volume constraints are effective in limiting cardiac events for left breast RT. Further studies and continued follow-up are necessary to confirm these observations.