Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study

Purpose The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established. Methods Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute). Results The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001). Conclusion Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.