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1.  Neurocognitive Functioning in Adult Survivors of Childhood Non-Central Nervous System Cancers 
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 ≥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.
doi:10.1093/jnci/djq156
PMCID: PMC2886093  PMID: 20458059
2.  Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report from the Childhood Cancer Survivor Study 
Neuropsychology  2009;23(6):705-717.
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.
Participants & Methods
As part of the Childhood Cancer Survivor Study (CCSS), 802 survivors of childhood CNS malignancy, 5937 survivors of non-CNS malignancy and 382 siblings without cancer completed a 25 item Neurocognitive Questionnaire (CCSS-NCQ) at least 16 years post cancer diagnosis assessing task efficiency, emotional regulation, organizational skills and memory. Neurocognitive functioning in survivors of CNS malignancy was compared to that of non-CNS malignancy survivors and a sibling cohort. Within the group of CNS malignancy survivors, multiple linear regression was used to assess the contribution of demographic, illness and treatment variables to reported neurocognitive functioning and the relationship of reported neurocognitive functioning to educational, employment and income status.
Results
Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all factors assessed by the CCSS-NCQ than non-CNS cancer survivors or siblings (p<.01), with mean T scores of CNS malignancy survivors substantially more impaired that those of the sibling cohort (p<.001), with a large effect size for Task Efficiency (1.16) and a medium effect size for Memory (.68). Within the CNS malignancy group, medical complications, including hearing deficits, paralysis and cerebrovascular incidents resulted in a greater likelihood of reported deficits on all of the CCSS-NCQ factors, with generally small effect sizes (.22-.50). Total brain irradiation predicted greater impairment on Task Efficiency and Memory (Effect sizes: .65 and .63, respectively), as did partial brain irradiation, with smaller effect sizes (.49 and .43, respectively). Ventriculoperitoneal (VP) shunt placement was associated with small deficits on the same scales (Effect sizes: Task Efficiency .26, Memory .32). Female gender predicted a greater likelihood of impaired scores on 2 scales, with small effect sizes (Task Efficiency .38, Emotional Regulation .45), while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor with a moderate effect size (.64). CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p<.01), less household income (p<.001) and less full time employment (p<.001).
Conclusions
Survivors of childhood CNS malignancy are at significant risk for impairment in neurocognitive functioning in adulthood, particularly if they have received cranial radiation, had a VP shunt placed, suffered a cerebrovascular incident or are left with hearing or motor impairments. Reported neurocognitive impairment adversely affected important adult outcomes, including education, employment, income and marital status.
doi:10.1037/a0016674
PMCID: PMC2796110  PMID: 19899829
Neurocognitive functioning; brain tumors; CNS malignancies; Childhood Cancer Survivor Study
3.  Reliability and Validity of the Childhood Cancer Survivor Study Neurocognitive Questionnaire 
Cancer  2008;113(8):2188-2197.
Background
Up to 40% of childhood cancer survivors may experience neurocognitive impairment in one 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 7,121 members of the Childhood Cancer Survivor Study cohort (6,739 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 seven years prior to 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 between survivors who were at “high risk” for neurocognitive dysfunction, due to 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.
Condensed Abstract
Regular monitoring of neurocognitive functioning is recommended for pediatric cancer survivors exposed to cranial irradiation and/or antimetabolite chemotherapy. The Childhood Cancer Survivor Study - Neurocognitive Questionnaire appears to be a practical and efficient tool for such monitoring.
doi:10.1002/cncr.23809
PMCID: PMC2574840  PMID: 18792068
Childhood Cancer Survivor Study; neurocognitive; questionnaire; late effects

Results 1-3 (3)