Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers

Abstract

BACKGROUND We sought to measure self-reported neurocognitive functioning among survivors of non-central nervous system (CNS) childhood cancers, overall and compared with a sibling cohort, and to identify factors associated with worse functioning. METHODS In a retrospective cohort study, 5937 adult survivors of non-CNS cancers and 382 siblings completed a validated neuropsychological instrument with subscales in task efficiency, emotional regulation, organization, and memory. Scores were converted to T scores; scores in the worst 10% of siblings' scores (ie, T score > or =63) were defined as impaired. Non-CNS cancer survivors and siblings were compared with multivariable linear regression and log-binomial regression. Among survivors, log-binomial models assessed the association of patient and treatment factors with neurocognitive dysfunction. All statistical tests were two-sided. RESULTS Non-CNS cancer survivors had similar or slightly worse (<0.5 standard deviation) mean test scores for all four subscales than siblings. However, frequencies of impaired survivors were approximately 50% higher than siblings in task efficiency (13.0% of survivors vs 7.3% of siblings), memory (12.5% vs 7.6%), and emotional regulation (21.2% vs 14.4%). Impaired task efficiency was most often identified in patients with acute lymphoblastic leukemia who received cranial radiation therapy (18.1% with impairment), myeloid leukemia who received cranial radiation therapy (21.2%), and non-Hodgkin lymphoma (13.9%). In adjusted analysis, diagnosis age of younger than 6 years, female sex, cranial radiation therapy, and hearing impairment were associated with impairment. CONCLUSION A statistically and clinically significantly higher percentage of self-reported neurocognitive impairment was found among survivors of non-CNS cancers than among siblings.

Figure 1

Flow diagram of study participation. Participants were from the Childhood Cancer Survivor Study. CNS = central nervous system; NCQ = Neurocognitive Questionnaire.

Figure 2

Percentages and 95% confidence intervals of impaired neurocognitive functioning among participants, stratified by receipt of cranial radiation therapy (CRT), compared with siblings (P values are for comparisons with siblings). Subgroups were non-central nervous system (CNS) survivors treated with a CRT dose of greater than 18 Gy, non-CNS survivors treated with CRT dose of 18 Gy or less, non-CNS survivors who did not receive CRT, and siblings. Impaired functioning was defined by T scores of 63 or higher on the Neurocognitive Questionnaire.