Radiation therapy is a primary risk factor for late cardiac disease in children with cancer.
A new study reported in the Journal of Clinical Oncology and led by a Winship Cancer Institute of Emory University researcher demonstrates for the first time that applying the same radiation therapy dose to the heart’s substructures as a uniform dose to the whole heart in children with cancer puts them at higher risk for future heart complications.
Nearly 16,000 children under the age of 20 are diagnosed with cancer yearly in the U.S., with approximately 85% becoming five-year survivors. Although the cure rates of childhood cancer have significantly improved over the past several decades, nearly every childhood cancer survivor develops a severe, life-threatening or fatal late complication from their treatment course. Cardiac disease is the most common of these late complications, and radiation therapy is a primary risk factor for late cardiac disease.
The current understanding of radiation dosage only considers the heart as a single organ and ignores its various substructures, such as the ventricles, atria, coronary arteries and valves. There is no established guidance for safe, effective radiation dosage for heart substructures. This study underscores the need to consider cardiac substructure doses in radiation treatment planning and in survivorship care.
Winship radiation oncologist and Cancer Prevention and Control researcher James Edward Bates, MD, assistant professor in the Department of Radiation Oncology at Emory University School of Medicine, and his colleagues show that the heart’s substructures may be more sensitive to the harmful effects of radiation than considering the heart as a single uniform organ, which is the typical approach taken by radiation oncologists today.
The study of 25,481 five-year survivors of childhood cancer treated from 1970-1999 in the Childhood Cancer Survivor Study represents the largest analysis ever of this kind and the first to contain a broad, heterogenous group of children treated for a variety of cancers. It is also the largest study, adult or pediatric, analyzing the impact of radiation doses to cardiac substructures across multiple primary cancer diagnoses.
Their modeling suggests that there may be a threshold dose below which radiation to the whole heart does not meaningfully increase the risk of coronary artery disease, arrhythmia, or valvular disease; however, there appears to be no “safe” threshold radiation dose when considering many cardiac substructures. Most notably, the right coronary artery and left ventricle appear very sensitive; each 1 Gy—the international system unit of radiation dose, expressed as absorbed energy per unit mass of tissue—increase in mean dose to either structure increases the risk of late coronary artery disease by 28.7% and 28.4% respectively.
Advanced radiation techniques, such as intensity modulated radiation or proton therapy, permit significantly increased precision in treatment planning. This precision allows for targeting specific areas of the heart rather than the entire organ.
"This research will allow radiation oncologists to better leverage modern radiation techniques, such as proton therapy and intensity-modulated radiation therapy (IMRT), to maximally reduce the risk of cardiac disease in children with cancer who require radiation,” says Bates. “Future work to ascertain optimal cardiac dose constraints remains critical."
The research was supported by the National Cancer Institute (CA55727); R01-CA261750; R01-216354; the Cancer Center Support Grant CA21765; and the American Lebanese-Syrian Associated Charities (ALSAC).