Background Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity among survivors, however, has not been described. Methods Among 5,522 patients treated for childhood cancer at St. Jude Children’s Research Hospital who survived ≥10 years and were ≥18 years old, 3,010 underwent prospective clinical assessment and retrospective medical validation of health records as part of the St. Jude Lifetime Cohort Study. Age- and sex-frequency-matched community-controls (n=272) were used for comparison. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs among the 2512 survivors not clinically evaluated. Mean cumulative count and marked-point-process regression were used for descriptive and inferential cumulative burden analyses, respectively. Findings The cumulative incidence of any grade CHC at age 50 was 99·9%; 96·0% (95·3%–96·8%) for severe/disabling, life-threatening or fatal CHCs. By age 50, a survivor experienced, on average, 17·1 (16·2–18·0) CHCs including 4·7 (4·6–4·9) graded as severe/disabling, life-threatening or fatal. The cumulative burden among survivors was nearly 2-fold greater than matched community-controls (p<0·001). Second neoplasms, spinal disorders and pulmonary disease were major contributors to the excess total cumulative burden. Significant heterogeneity in CHCs among survivors with differing primary cancer diagnoses was observed. Multivariable analyses demonstrated that age at diagnosis, treatment era and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. Interpretation The burden of surviving childhood cancer is substantial and highly variable. The total cumulative burden experienced by survivors of pediatric cancer, in conjunction with detailed characterization of long-term CHCs, provide data to better inform future clinical guidelines, research investigations and health services planning for this vulnerable, medically-complex population.

A B S T R A C T PurposeTo determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and MethodsSurvivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age Ն 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. ResultsImpairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values Ͻ .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. ConclusionThis study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.

The diagnosis, treatment, and medical late effects of childhood cancer may alter the psychosocial trajectory of survivors across their life course. This review of the literature focuses on mental health symptoms, achievement of social milestones, socioeconomic attainment, and risky health behaviors in survivors of childhood cancer. Results suggest that although most survivors are psychologically well adjusted, survivors are at risk for anxiety and depression compared with siblings. Although the absolute risk of suicide ideation and post-traumatic stress symptoms is low, adult survivors are at increased risk compared with controls. Moreover, young adult survivors are at risk for delayed psychosexual development, lower rates of marriage or cohabitation, and nonindependent living. Survivors' socioeconomic attainment also is reduced, with fewer survivors graduating college and gaining full-time employment. Despite risk for late health-related complications, survivors of childhood cancer generally engage in risky health behaviors at rates similar to or only slightly lower than siblings and peers. CNS tumors and CNS-directed therapies are salient risk factors for poor psychosocial outcomes. In addition, physical health morbidities resulting from cancer-directed therapies are associated with worse psychosocial functioning. Several studies support the effectiveness of cognitive and behavioral interventions to treat psychological symptoms as well as to modify health behaviors. Additional randomized controlled trials are needed to evaluate the efficacy and long-term outcomes of intervention efforts. Future research should focus on the identification of potential genetic predispositions related to psychosocial outcomes to provide opportunities for preventive interventions among survivors of childhood cancer.