Cardiovascular Disease in Adult Survivors of Childhood and Adolescent Cancer: A Report from the Childhood Cancer Survivor Study (CCSS)

Sarah S. Donaldson, Stanford University Medical Center 
Daniel M. Green, St. Jude Children's Research Hospital 
Toana Kawashima, Fred Hutchinson Cancer Research Center 
Wendy M. Leisenring, Fred Hutchinson Cancer Research Center 
Ann C. Mertens, Emory University 
Pauline Mitby, Children's Hospitals and Clinics of Minnesota 
*Daniel A. Mulrooney, St. Jude Children's Research Hospital 
Leslie L. Robison, St. Jude Children's Research Hospital 
Charles A. Sklar, Memorial Sloan-Kettering Cancer Center 
Marilyn Stovall, University of Texas MD Anderson Cancer Center 
Mark W. Yeazel, University of Minnesota 

Keywords: Childhood Cancer, Survivors, Cardiovascular disease

Background: Previous research has shown that cardiovascular disease contributes to significant morbidity and mortality among survivors of childhood and adolescent cancer. Few studies have reported risk factors in long-term survivors who are now adults.

Methods: This analysis includes 14,358 five-year cancer survivors of the CCSS diagnosed = age 21, between 1970-1986, with one of eight childhood cancers [leukemia, CNS tumors, Hodgkin (HD) or non-Hodgkin lymphomas (NHL), renal tumors, neuroblastoma, soft-tissue sarcomas (STS), bone cancers]. Self-reported cardiac outcomes occurring at least 5-years post-dx are compared to a sibling control group (N=3899) and across treatment groups using Cox proportional hazards models to estimate relative risks (RR) adjusted for age, gender, race, sociodemographic factors, and smoking status.

Results: Survivors (54% males) were on average 7.8 yrs (0-20) at diagnosis, and 27.5 yrs (8-51) at follow-up. Compared to siblings, survivors were more likely to report congestive heart failure (CHF) (RR 5.9 95% CI 3.4-9.6), myocardial infarction (MI) (RR 5.0 95% CI 2.3-10.4), atherosclerosis (RR 10.2 95% CI 3.7-28.3), pericardial (RR 6.3 95% CI 3.3-11.9) and valvular disease (RR 4.8 95% CI 3.0-7.6), and coronary angiography (RR 8.2 95% CI 4.2-16.1). Anthracycline exposure = 250 mg/m2 increased the risk of reported CHF (RR 5.2 95% CI 3.6-7.4), pericardial (RR 1.8 95% CI 1.1-3.0) and valvular disease (RR 2.3 95% CI 1.6-3.3), and angiography (RR 2.6 95% CI 1.8-3.7) compared to unexposed survivors. Radiation (RT) to the heart also increased the risk of CHF (RR 2.0 95% CI 1.4-2.8), MI (RR 1.9 95% CI 1.1-3.2), atherosclerosis (RR 5.3 95% CI 2.5-11.0), pericardial (RR 2.2 95% CI 1.4-3.3) and valvular disease (RR 2.8 95% CI 1.9-4.0), and angiography (RR 2.2 95% CI 1.5-3.2) compared to those survivors without cardiac directed RT.

Conclusion: The occurrence of premature cardiovascular diseases is substantial in this young adult population of cancer survivors.