TY - JOUR
T1 - Cardiac Disease in Childhood Cancer Survivors Treated With Radiation Therapy
T2 - A PENTEC Comprehensive Review
AU - Bates, James E.
AU - Rancati, Tiziana
AU - Keshavarz, Homa
AU - Gagliardi, Giovanna
AU - Aznar, Marianne C.
AU - Howell, Rebecca M.
AU - Shrestha, Suman
AU - Moiseenko, Vitali
AU - Yorke, Ellen
AU - Armenian, Saro
AU - Kremer, Leontien
AU - Chen, Ming Hui
AU - van der Pal, Helena J.
AU - Cutter, David J.
AU - Constine, Louis S.
AU - Hodgson, David
N1 - Funding Information: M.C.A. acknowledges the support of the Engineering and Physical Research Council (grant number EP/T028017/1 ). E.Y. acknowledges the support of Memorial Sloan Kettering Cancer Center's Cancer Center Support Grant ( NIH/NCI P30 CA008748 ). D.J.C. is supported by Cancer Research UK ( C8225/A21133 , PRCRPG-Nov21\100001 ) and the University of Oxford . Publisher Copyright: © 2023 Elsevier Inc.
PY - 2023
Y1 - 2023
N2 - Purpose: Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT. Methods and Materials: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We identified 1496 articles; 4 were included for dose-response modeling between mean cardiac radiation dose and risk of late coronary artery disease, heart failure (HF), valvular disease, and any cardiac disease. Results: For each 10-Gy increase in corrected mean cardiac radiation dose in 1.8- to 2.0-Gy fractions, we estimated a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25) for coronary artery disease, of 1.87 (95% CI, 1.70-2.06) for HF, of 1.87 (95% CI, 1.78-1.96) for valvular disease, and of 1.88 (95% CI, 1.75-2.03) for any cardiac disease. From the same model, for each 100-mg/m2 increase in cumulative anthracycline dose, the hazard ratio for the development of HF was 1.93 (95% CI, 1.58-2.36), equivalent to an increase in mean heart dose of approximately 10.5 Gy. Other nontreatment factors were inconsistently reported in the analyzed articles. Conclusions: Radiation dose to the heart increases the risk of late cardiac disease, but survivors of childhood cancer who receive a mean dose <10 Gy at standard fractionation are at low absolute risk (<∼2% approximately 30 years after exposure) of late cardiac disease in the absence of anthracycline exposure. Minimizing cardiac radiation dose is especially relevant in children receiving anthracyclines. When cardiac sparing is not possible, we recommend prioritizing target coverage. It is likely that individual cardiac substructure doses will be a better predictor of specific cardiac diseases than mean dose, and we urge the pediatric oncology community to further study these relationships.
AB - Purpose: Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT. Methods and Materials: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We identified 1496 articles; 4 were included for dose-response modeling between mean cardiac radiation dose and risk of late coronary artery disease, heart failure (HF), valvular disease, and any cardiac disease. Results: For each 10-Gy increase in corrected mean cardiac radiation dose in 1.8- to 2.0-Gy fractions, we estimated a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25) for coronary artery disease, of 1.87 (95% CI, 1.70-2.06) for HF, of 1.87 (95% CI, 1.78-1.96) for valvular disease, and of 1.88 (95% CI, 1.75-2.03) for any cardiac disease. From the same model, for each 100-mg/m2 increase in cumulative anthracycline dose, the hazard ratio for the development of HF was 1.93 (95% CI, 1.58-2.36), equivalent to an increase in mean heart dose of approximately 10.5 Gy. Other nontreatment factors were inconsistently reported in the analyzed articles. Conclusions: Radiation dose to the heart increases the risk of late cardiac disease, but survivors of childhood cancer who receive a mean dose <10 Gy at standard fractionation are at low absolute risk (<∼2% approximately 30 years after exposure) of late cardiac disease in the absence of anthracycline exposure. Minimizing cardiac radiation dose is especially relevant in children receiving anthracyclines. When cardiac sparing is not possible, we recommend prioritizing target coverage. It is likely that individual cardiac substructure doses will be a better predictor of specific cardiac diseases than mean dose, and we urge the pediatric oncology community to further study these relationships.
UR - http://www.scopus.com/inward/record.url?scp=85152745798&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijrobp.2023.03.045
DO - https://doi.org/10.1016/j.ijrobp.2023.03.045
M3 - Article
C2 - 37061912
SN - 0360-3016
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
ER -