Models that included factors such as age at diagnosis, anthracycline doses, and radiation fields and doses accurately predicted risk for congestive heart failure in childhood cancer survivors through age 40 years, according to study results.
Eric J. Chow, MD, MPH, an assistant member of the clinical research division at Fred Hutchinson Cancer Research Center, and colleagues evaluated data from 13,060 cancer survivors enrolled in the Childhood Cancer Survivor Study. All survivors were free of significant cardiovascular disease 5 years after cancer diagnosis.
Researchers also included 4,023 of the survivors’ siblings for comparison.
Most of the cancer survivors were aged younger than 5 years at diagnosis (40.2%). The most common cancer diagnoses were acute lymphoblastic leukemia (30.5%), Hodgkin’s lymphoma (13.4%) and brain tumors (12.9%).
More than one-third of the survivors (37.3%) had been treated with an anthracycline, which included doxorubicin, daunorubicin, idarubicin, epirubicin and mitoxantrone. About one-quarter (25.9%) of the survivors had received chest radiation therapy.
Median follow-up on the Childhood Cancer Survivor Study was 19 years (range, 0-34). The median age of survivors at last follow-up was 32 years (range, 6-59), and the median age of siblings was 34 years (range, 3-63).
Overall, 285 survivors developed congestive heart failure by age 40 years, which equated to a cumulative incidence of 2.8% (95% CI, 2.4-3.2). However, only 12 siblings had heart failure (cumulative incidence, 0.3%; 95% CI, 0.1-0.5).
Researchers used data from these individuals to create simple, standard and heart dose models of congestive heart failure predictors. The heart dose model incorporated data about the average radiation dose to the heart in place of chest field dose.
Elevated risks for heart failure in the heart dose model included age younger than 5 years at diagnosis (RR=2.6; 95% CI, 1.6-4.1), female sex (RR=1.7; 95% CI, 1.3-2.1), anthracycline dose ≥250 mg/m2 (RR=10.5; 95% CI, 7.7-14.4) and receipt of radiation therapy ≥35 Gy (RR=10.5; 95% CI, 7.2-15.4).
Researchers calculated an area under the curve of 0.76 and a concordance statistic of 0.77 for the heart dose model through age 40 years.
Analyses from a validation cohort of 3,421 survivors from Emma Children’s Hospital in the Netherlands, the National Wilms’ Tumor Study and the St. Jude Lifetime Cohort study demonstrated an area under the curve ranging from 0.68 to 0.81 and a concordance statistic ranging from 0.68 to 0.82 for the standard and heart dose models.
Researchers then used the risk scores to create low-risk (cumulative incidence, 0.5%; 95% CI, 0.2-0.8), moderate-risk (cumulative incidence, 2.4%; 95% CI, 1.8-3) and high-risk groups (cumulative incidence, 11.7%; 95% CI, 8.8-14.5) for heart failure by age 40 years.
“Although there remains a paucity of evidence regarding the optimal screening strategy and the most appropriate intervention should abnormalities be detected, the Childhood Cancer Survivor Study-Congestive Heart Failure prediction models provide a robust framework for personalized risk assessment,” Chow and colleagues concluded. “These models may help refine cardiomyopathy surveillance by reducing screening among low-risk survivors while identifying higher-risk individuals who may benefit from closer follow-up. Further, they can serve as a platform to test interventions designed to reduce congestive heart failure-related morbidity.”
Disclosure: The researchers report no relevant financial disclosures.