Coronary Heart Disease after Irradiation for sn Enlarged Thymus: Results from the Hempelmann Cohort

*Michael Jacob Adams, MD, MPH, University of Rochester School of Medicine and Dentistry 
Robert Block, University of Rochester School of Medicine and Dentistry 
Louis S. Constine, University of Rochester School of Medicine and Dentistry 
Ann Dozier, University of Rochester School of Medicine and Dentistry 
Susan G. Fisher, University of Rochester School of Medicine and Dentistry 
Steven E. Lipshultz, University of Miami/Jackson Memorial Hospital 
Thomas A. Pearson, University of Rochester School of Medicine and Dentistry 
Ronald G. Schwartz, University of Rochester School of Medicine and Dentistry 
Roy E. Shore, Radiation Effects Research Foundation, Minami-ku 
Marilyn Stovall, University of Texas MD Anderson Cancer Center 
Kelly Thevenet-Morrison, University of Rochester School of Medicine and Dentistry 

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Background: Studies of cancer survivors and those with peptic ulcer disease treated with older radiotherapy (RT) techniques strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago. Additionally, a nested pilot study was performed to evaluate whether highly-sensitive C reactive Protein, body mass index or components of total cholesterol differed between irradiated individuals and their siblings.

Methods: A population-based, longitudinal cohort of subjects exposed to irradiation for an enlarged thymus during infancy from 1926 to 1957 and of their non-irradiated siblings was reestablished between 2004 and 2008. Coronary heart disease (CHD) events were assessed using a mailed survey and checking cause of death in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose.

Results: Median age and length of follow-up was 57.5 years (range 41.2-88.8 yrs) among both irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gy (range 0.17-20.20 Gy). During a combined 335,235 person-years of follow-up, 215 myocardial infarctions (MI) and 351 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age and gender, the rate ratio for MI incidence was 0.99 (95%CI: 0.75-1.30), and for all CHD events was 1.09 (95%CI: 0.88-1.35). The estimated adjusted excess relative risks for MI and all CHD events were -0.03 (95%CI: -0.12-0.10) and 0.07 (95%CI: -0.02-0.18), respectively at 1 Gy. In our pilot study, amongst the biomarkers measured only HDL cholesterol was significantly different between thymus-irradiated individuals and their siblings. Breast cancer incidence and thyroid cancer incidence data from the last follow-up will also be reviewed

Conclusions: These preliminary results suggest reduction of cardiac radiation doses to the levels in our cohort without increasing other cardiotoxic therapies may eliminate or at least delay into the 7th decade of life increased CHD risk. Thyroid cancer and breast cancer cumulative incidence was still greater in the irradiated individuals with the relative risk still apparently increasing for breast cancer.