Kyle Wang1, Kevin A Pearlstein2, Nicholas D Patchett3, Allison M Deal4, Panayiotis Mavroidis2, Brian C Jensen5, Matthew B Lipner2, Timothy M Zagar2, Yue Wang4, Carrie B Lee6, Michael J Eblan7, Julian G Rosenman2, Mark A Socinski8, Thomas E Stinchcombe9, Lawrence B Marks2. 1. Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, United States. Electronic address: kyle.wang@unchealth.unc.edu. 2. Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, United States. 3. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States. 4. Lineberger Comprehensive Cancer Center Biostatistics Core, University of North Carolina Hospitals, Chapel Hill, United States. 5. Department of Medicine, Division of Cardiology, University of North Carolina Hospitals, Chapel Hill, United States. 6. Department of Medicine, Division of Hematology/Oncology, University of North Carolina Hospitals, Chapel Hill, United States. 7. Department of Radiation Oncology, Inova Schar Cancer Institute, Falls Church, United States. 8. Florida Hospital Cancer Institute, Orlando, United States. 9. Department of Medicine, Division of Hematology/Oncology, Duke University Hospitals, Durham, United States.
Abstract
BACKGROUND AND PURPOSE: To assess associations between radiation dose/volume parameters for cardiac subvolumes and different types of cardiac events in patients treated on radiation dose-escalation trials. MATERIAL AND METHODS: Patients with Stage III non-small-cell lung cancer received dose-escalated radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective trials from 1996 to 2009. Volumes analyzed included whole heart, left ventricle (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into three categories: pericardial (symptomatic effusion and pericarditis), ischemia (myocardial infarction and unstable angina), and arrhythmia. Univariable competing risks analysis was used. RESULTS: 112 patients were analyzed, with median follow-up 8.8 years for surviving patients. Nine patients had pericardial, seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial events were correlated with whole heart, RA, and LA dose (eg, heart-V30 [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart-V30 [p=0.048]). Arrhythmic events showed borderline significant associations with RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30 [p=0.051]). Cardiac events were associated with decreased survival on univariable analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased survival on multivariable analysis. CONCLUSIONS: Cardiac events were heterogeneous and associated with distinct heart subvolume doses. These data support the hypothesis of distinct etiologies for different types of radiation-associated cardiotoxicity.
BACKGROUND AND PURPOSE: To assess associations between radiation dose/volume parameters for cardiac subvolumes and different types of cardiac events in patients treated on radiation dose-escalation trials. MATERIAL AND METHODS:Patients with Stage III non-small-cell lung cancer received dose-escalated radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective trials from 1996 to 2009. Volumes analyzed included whole heart, left ventricle (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into three categories: pericardial (symptomatic effusion and pericarditis), ischemia (myocardial infarction and unstable angina), and arrhythmia. Univariable competing risks analysis was used. RESULTS: 112 patients were analyzed, with median follow-up 8.8 years for surviving patients. Nine patients had pericardial, seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial events were correlated with whole heart, RA, and LA dose (eg, heart-V30 [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart-V30 [p=0.048]). Arrhythmic events showed borderline significant associations with RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30 [p=0.051]). Cardiac events were associated with decreased survival on univariable analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased survival on multivariable analysis. CONCLUSIONS: Cardiac events were heterogeneous and associated with distinct heart subvolume doses. These data support the hypothesis of distinct etiologies for different types of radiation-associated cardiotoxicity.
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