Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study

Abstract

Purpose: To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures.

Patients and methods: Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the χ(2) test. Log-binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment.

Results: In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living.

Conclusion: Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones.

Fig 1.

CONSORT diagram of study participation.

Fig 2.

Degree of neurocognitive impairment in adult survivors of childhood CNS tumors by cranial radiation exposure. (A) No cranial radiation therapy (CRT; n = 63). (B) Focal irradiation (n = 71). (C) Craniospinal irradiation (CSI; n = 83).

Fig 3.

Neurocognitive performance by cranial radiation exposure. Medians, interquartile ranges, and individual z scores plotted for each exposure by outcome. The y-axis intervals are extended for sustained attention and verbal fluency to account for extreme values. 2DRT, two-dimensional treatment planning; 3DCRT, three-dimensional conformal radiation therapy; CRT, cranial radiation therapy; CSI, craniospinal irradiation; IQ, intelligence quotient.