Self-reported and parent proxy reported functional impairment among pediatric cancer survivors and controls.

BACKGROUND: A unique and limiting component in the research on functional impairment among children has been the exclusive use of parent proxy reports about child functioning; and there is limited information regarding the impact of pediatric cancer treatment on children's day-to-day functioning and how this is related to neurocognitive functioning. The objective of the current study was to examine a novel measure of self-reported functional impairment, and explore the relationship between self-reported and parent-reported child functional impairment in pediatric cancer survivors compared to controls. METHODS: A cross-sectional cohort of survivors (n = 26) and controls (n = 53) were recruited. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1-15 years) and demonstrated an average "medium" Central Nervous System treatment intensity score. Participants completed measures of functional impairment (FI), intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children's functional impairment. RESULTS: Survivors were similar to controls in functional impairment. Regardless of group membership, self-reported FI was higher than parent-reported FI, although they were correlated and parent report of FI significantly predicted self-reported FI. Across groups, increased impairment was associated with four of seven Examiner scores. CONCLUSIONS: Research regarding self-reported functional impairment of cancer survivors and its association with parent-reported functional impairment and neurocognitive deficits has been limited. Our results suggest that self-reported FI appears to be a reasonable and viable outcome measure that corresponds with and adds incremental validity to parent reported FI. While low treatment intensity may confer relative sparing of functional impairment among survivors, children report higher FI levels than parents, suggesting that FI can be of clinical utility. In conclusion, pediatric cancer survivors should be screened for self-reported functional difficulties.

Neuropsychological functioning of children treated for acute lymphoblastic leukemia: impact of whole brain radiation therapy.

OBJECTIVES: To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared. METHODS: This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105. RESULTS: Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p < 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p < 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis. CONCLUSIONS: The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.

Parental stress predicts functional outcome in pediatric cancer survivors.

BACKGROUND: Childhood cancer survivors are at risk for long-term neurocognitive and psychosocial morbidities. Research has seldom examined the relationship between these morbidities; thus, little empirical evidence exists concerning overall salience and how morbidities converge to impair day-to-day functioning. An increased understanding of functional impairment resulting from the pediatric cancer experience can inform early risk identification as well as sources for intervention. The purpose of this study was to characterize the frequency/severity of functional impairment and identify significant neurocognitive and psychosocial determinants of functional impairment. METHODS: Fifty child-parent dyads were enrolled. Children were aged 7-19 years who were at least 2 years postdiagnosis with leukemia/lymphoma and were recruited through a pediatric oncology late effects clinic. Parents completed questionnaires, rating their own adjustment to their child's illness as well as their child's level of functional impairment, while a brief neuropsychological exam was administered to children. RESULTS: Twenty-six percent of the sample evidenced clinically significant functional impairment. Regression analyses indicated that neurocognitive deficits did not predict functional impairment, whereas parental stress was a significant predictor. CONCLUSIONS: Although children demonstrated both neurocognitive deficits and functional impairments, results favor psychosocial factors, such as parental stress, as a predictor of overall functional impairment. The implications of this study suggest that late effects aggregate to impact day-to-day functioning in pediatric cancer survivor populations and parental stress may serve as a marker for heightened risk. The results suggest that broader functional domains, especially school and self-care domains, should be evaluated and considered when identifying potential targets for psychosocial interventions.

Normalized Cortisol Reactivity Predicts Future Neuropsychological Functioning in Children With Mild/Moderate Asthma.

Cortisol reactivity to adrenocorticotropic hormone (ACTH) has been associated with neuropsychological processes including attention and memory in children with asthma. While cortisol reactivity to a psychological stressor is often considered a measure of current neuroendocrine functioning, this study examines the association of the cortisol reactivity and subsequent neuropsychological functioning. Using prospective data from the Childhood Asthma Management Program (CAMP), we explored the predictive ability of cortisol reactivity to ACTH and children's later attention and memory using traditional and an alternative cortisol reactivity (normalized cortisol) measures. Cortisol reactivity was assessed at study entry and 1-year follow-up, and neuropsychological functioning was assessed at 3-year follow-up. Cortisol reactivity was assessed through plasma cortisol concentrations collected at baseline (CORTBASELINE) and 30 min post-ACTH challenge (CORTPOST-A CTH). An alternative measure of cortisol reactivity was developed through post-ACTH stimulation cortisol, normalized by cortisol by baseline (CORTNORM -ACTH). CORT B ASELINE positively predicted year 3 attention, while CORTNORM -ACTH negatively predicted attention, suggesting convergence of cortisol variables in prediction of neuropsychological function. Year 1 CORTACTH positively predicted child memory at year 3; Year 1 CORTNORM-ACTH negatively predicted year 3 sustained attentions. These findings demonstrate that HPA reactivity, including the application of normalized cortisol reactivity, can predict subsequent neuropsychological functioning of children with mild to moderate asthma.

Association Between Executive Functioning and Functional Impairment Among Pediatric Cancer Survivors and Controls.

OBJECTIVE: To examine the impact of cancer treatment upon neurocognitive and functional impairment; and to explore the relationship between these constructs in pediatric cancer survivors compared to controls. METHOD: A cross-sectional cohort of survivors (n = 26) and controls (n = 53) was included. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1-15 years) and demonstrated an average "medium" Central Nervous System (CNS) treatment intensity score. Participants completed measures of neurocognitive functions including intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children's functional impairment (BIS). RESULTS: Survivors were similar to controls in neurocognitive ability, including intellectual and executive functions, and functional impairment. Regardless of group membership, NIH Examiner performance and functional impairment increased with age. Increased impairment was associated with different neurocognitive variables for survivors versus controls. CONCLUSIONS: Research regarding functional impairment of cancer survivors and the association between neurocognitive deficits and functional impairment has been limited. Our results demonstrate that, while low treatment intensity may confer relative sparing of neurocognitive and executive functioning among survivors, functional impairment continues to be a potential risk. In conclusion, pediatric cancer survivors should be screened for functional difficulties, particularly in the areas of interpersonal relations and self-care.