TY - JOUR
T1 - Cardiac Substructure Radiation Dose and Risk of Late Cardiac Disease in Survivors of Childhood Cancer
T2 - A Report From the Childhood Cancer Survivor Study
AU - Bates, James E.
AU - Shrestha, Suman
AU - Liu, Qi
AU - Smith, Susan A.
AU - Mulrooney, Daniel A.
AU - Leisenring, Wendy
AU - Gibson, Todd
AU - Robison, Leslie L.
AU - Chow, Eric J.
AU - Oeffinger, Kevin C.
AU - Armstrong, Gregory T.
AU - Constine, Louis S.
AU - Hoppe, Bradford S.
AU - Lee, Choonsik
AU - Yasui, Yutaka
AU - Howell, Rebecca M.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - PURPOSERadiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.METHODSUsing the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.RESULTSThe cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD.CONCLUSIONAmong children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.
AB - PURPOSERadiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.METHODSUsing the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.RESULTSThe cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD.CONCLUSIONAmong children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.
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U2 - 10.1200/JCO.22.02320
DO - 10.1200/JCO.22.02320
M3 - Article
C2 - 37307512
AN - SCOPUS:85166362271
SN - 0732-183X
VL - 41
SP - 3826
EP - 3838
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -