Treatment exposure-based risk-stratification for care of survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Treatment exposure-based risk-stratification of long-term cancer survivors may help inform health care in survivorship clinics. We used the large, diverse population of the Childhood Cancer Survivor Study to test a modified, exposure-based strata previously developed within United Kingdom to classify survivors with respect to risk of late morbidity and health-related mortality. METHODS: Five-year survivors of childhood cancer were categorized into low-, medium-, and high-risk groups based on treatment exposures and diagnosis. Primary endpoints included cumulative health-related (ie, nonrecurrence, nonexternal) late mortality and cumulative incidence of severe or fatal (CTCAE grade 3-5) chronic health conditions conditional on reaching age 20 without the outcome. Siblings were a comparison group for chronic health conditions. Cox proportional hazards models were adjusted for sex, race, ethnicity, and age at diagnosis. RESULTS: Among 15,346 survivors diagnosed 1970-1999, the risk of developing a severe chronic condition by age 35 was 11.9% (95% confidence interval [CI] = 9.9% to 14.3%), 15.1% (13.7% to 16.6%), and 25.4% (24.3% to 26.5%) for low-, medium-, and high-risk survivors, respectively, and 6.9% (6.1% to 7.9%) for siblings. Multivariable analysis confirmed higher likelihood of developing a chronic condition in high (hazard ratio [HR] = 2.9, 2.5 to 3.4) and medium (HR = 1.5, 1.3 to 1.8) versus the low-risk group. Health-related mortality was similarly increased among high (HR = 5.1, 3.8 to 7.0) and medium (HR = 2.5, 1.8 to 3.4) risk groups, as well as Black versus Non-Hispanic White survivors (HR = 1.7, 1.3 to 2.1). CONCLUSIONS: Exposure-based risk categorizations can provide generalized risk stratification regarding future chronic health conditions and early mortality and may be useful in guiding management of childhood cancer survivors.

Duke Scholars

Author Michaela Ann Dinan Population Health Sciences

Author Kevin Charles Oeffinger Medicine, Medical Oncology