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

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 (CCSS) 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. 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, non-recurrence, non-external) 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. Among 15,346 survivors diagnosed 1970-1999, the risk of developing a severe chronic condition by age 35 was 11.9% (95% CI 9.9-14.3%), 15.1% (13.7-16.6%) and 25.4% (24.3-26.5%) for low, medium, and high-risk survivors, respectively, and 6.9% (6.1-7.9%) for siblings. Multivariable analysis confirmed higher likelihood of developing a chronic condition in high (hazard ratio [HR] 2.9, 2.5- 3.4) and medium (HR 1.5, 1.3- 1.8) vs the low-risk group. Health-related mortality was similarly increased among high (HR 5.1, 3.8-7.0) and medium (HR 2.5, 1.8-3.4) risk groups, as well as Black vs Non-Hispanic White survivors (HR 1.7, 1.3-2.1). 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.