Kyle Wang1, Hayley E Malkin2, Nicholas D Patchett3, Kevin A Pearlstein2, Hillary M Heiling4, Sean D McCabe4, Allison M Deal4, Panayiotis Mavroidis2, Mary Oakey2, Jeffrey Fenoli2, Carrie B Lee5, J Larry Klein6, Brian C Jensen7, Thomas E Stinchcombe8, Lawrence B Marks2, Ashley A Weiner2. 1. Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio. Electronic address: kwang545@gmail.com. 2. Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina. 3. Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 4. Lineberger Comprehensive Cancer Center Biostatistics Core, University of North Carolina, Chapel Hill, North Carolina. 5. Department of Internal Medicine, Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina. 6. Department of Internal Medicine, Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina; Department of Radiology, University of North Carolina, Chapel Hill, North Carolina. 7. Department of Internal Medicine, Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina. 8. Duke Cancer Institute, Division of Medical Oncology, Duke University, Durham, North Carolina.
Abstract
PURPOSE: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. CONCLUSIONS: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.
PURPOSE: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. CONCLUSIONS: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.
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