Background-Among survivors of childhood cancer, those with Central Nervous System (CNS) malignancies have been found to be at greatest risk for neuropsychological dysfunction in the first few years following diagnosis and treatment. This study follows survivors to adulthood to assess the long term impact of childhood CNS malignancy and its treatment on neurocognitive functioning.

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.

BACKGROUND. Up to 40% of childhood cancer survivors may experience neurocognitive impairment in 1 or more specific domains. As such, regular monitoring has been recommended for patients exposed to cranial irradiation and/or antimetabolite chemotherapy. This study reports the results of a questionnaire developed to identify those survivors who may be experiencing neurocognitive problems. METHODS. Participants for this study were 7121 members of the Childhood Cancer Survivor Study cohort (6739 survivors and 382 siblings). These participants completed a new neurocognitive questionnaire designed to assess functions commonly affected by cancer therapy, as well as a standard measure of emotional functioning. A measure of cognitive and emotional functioning was also completed on a subset of the patients roughly 7 years before the current questionnaire. Responses to the questionnaires among subgroups of survivors were then analyzed to examine the reliability and validity of the new neurocognitive questionnaire. RESULTS. Four reliable factors were identified that assessed task efficiency, emotional regulation, organization, and memory skills. These neurocognitive factors accurately discriminated survivors who were at “high risk” for neurocognitive dysfunction, because of neurologic abnormalities or a history of intensive focal cranial irradiation, from healthy “low‐risk” survivors and siblings. CONCLUSIONS. The questionnaire demonstrated excellent reliability, as well as construct and discriminative validity. It appears to be a practical and efficient tool for monitoring neurocognitive outcomes in adult survivors of pediatric cancer. Cancer 2008. © 2008 American Cancer Society.

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