Risk of Ischemic Heart Disease in Patients After Conccurent Chemoradiotherapy for Lung and Esophageal Cancer: A Case-Control Study

Abstract

Late cardiac toxicity after thoracic radiotherapy is an important problem because the number of long-term survivors are increasing due to advances in medicine. However, little is known about the effect of incidental exposure of the heart to radiation on the risk of subsequent ischemic heart disease. Purpose of this study was to investigate the relationship between cardiac radiation dose and major adverse cardiovascular event (MACE). We conducted a case-control study of MACE in patients who underwent definitive thoracic radiotherapy for lung or esophageal cancer between September 2002 to December 2005 at our institution. MACE were defined as myocardial infarction, coronary revascularization, or death from ischemic heart disease. To minimize selection bias between MACE and non-MACE group, a propensity score matching was used based on the following covariates: age, sex, smoking history, and history of ischemic heart disease. The mean heart dose (MHD) was recalculated using original volumetric CT simulation images and radiotherapy planning system. Beam arrangements, energy, and monitor units were simulated based on the patient’s radiotherapy record. Among 543 patients, 14 patients developed MACE and 63 patients were included in the matched non-MACE cohort. Forty-seven and 30 patients had lung and esophageal cancer, respectively. All patients underwent three dimensional conformal radiotherapy with concurrent chemotherapy. Mean prescribed dose was 56 Gy. Median follow up time was 114.2 months. There was no statistically significant difference in overall survival rate between two groups. We set the cutoff value of 30 Gy in MHD by receiver operating characteristic curve analysis to predict MACE. There was a significant difference in the incident of MACE between high-MHD (>=30Gy) and low-MHD (<30Gy) groups (10.0 vs 47.1%, Fisher’s exact test, p=0.002). Patients in low-MHD group had a longer MACE-free survival than those in high-MHD group (94.8 months vs not-reached, Log-rank test p=0.044). Exposure of the heart to ionizing radiation in thoracic radiotherapy may increase the subsequent rate of ischemic heart disease.