Children surviving some types of cancer, particularly acute lymphoblastic leukemia (ALL) and brain tumors, have an increased incidence of learning impairments compared to their healthy peers in the general population. These impairments, for which there is no known effective treatment, are of sufficient severity to inhibit normal academic achievement, vocational attainment, and quality of life. Previous investigations have suggested a model in which treatment-induced lesions of the brain, especially in the white matter, are an underlying cause of learning difficulties that are frequently manifested as deficits in the ability to sustain attention. The goal of this research proposal is to test the validity of this model by defining the neuroanatomic substrates of problems with attention and learning and by assessing the behavioral response of these problems to pharmacological intervention. To accomplish this goal, quantitative magnetic resonance imaging (qMRI) of the brain and neuropsychological testing will be conducted on 625 participating children treated for ALL or malignant brain tumors at 3 pediatric cancer centers. It is hypothesized that volumes of normal white matter in patients will be: a) significantly reduced compared to healthy peers, b) directly associated with the intensity of their central nervous system treatment, and c) positively correlated with their performance on measures of sustained attention and learning. A second study hypothesis is that methylphenidate will be effective in reducing their problems with attention and learning. This hypothesis will be tested with 200 children selected from the larger screened sample on the basis of objective problems with sustained attention and learning with regard to: (a) immediate (1-1/2 hr) behavioral benefits in our laboratory and (b) short-term (3 week) benefits at home and school in randomized, placebo-controlled, crossover designs, and then (c) long-term (12 month) maintenance benefits at home and school. The results of these studies will have a potentially important impact on childhood cancer by reducing the cognitive morbidities of cancer and cancer treatment and by furthering our knowledge of their biological basis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078957-02
Application #
6174266
Study Section
Behavioral Medicine Study Section (BEM)
Program Officer
Aziz, Noreen M
Project Start
1999-07-12
Project End
2004-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
2
Fiscal Year
2000
Total Cost
$536,727
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Reddick, Wilburn E; Taghipour, Delaram J; Glass, John O et al. (2014) Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers. Pediatr Blood Cancer 61:1074-9
Moyer, Katherine H; Willard, Victoria W; Gross, Alan M et al. (2012) The impact of attention on social functioning in survivors of pediatric acute lymphoblastic leukemia and brain tumors. Pediatr Blood Cancer 59:1290-5
Netson, Kelli L; Conklin, Heather M; Ashford, Jason M et al. (2011) Parent and teacher ratings of attention during a year-long methylphenidate trial in children treated for cancer. J Pediatr Psychol 36:438-50
Palmer, Shawna L; Reddick, Wilburn E; Glass, John O et al. (2010) Regional white matter anisotropy and reading ability in patients treated for pediatric embryonal tumors. Brain Imaging Behav 4:132-40
Conklin, Heather M; Helton, Susan; Ashford, Jason et al. (2010) Predicting methylphenidate response in long-term survivors of childhood cancer: a randomized, double-blind, placebo-controlled, crossover trial. J Pediatr Psychol 35:144-55
Conklin, Heather M; Reddick, Wilburn E; Ashford, Jason et al. (2010) Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors. J Clin Oncol 28:4465-72
Jasper, Bruce W; Conklin, Heather M; Lawford, Joanne et al. (2009) Growth effects of methylphenidate among childhood cancer survivors: a 12-month case-matched open-label study. Pediatr Blood Cancer 52:39-43
Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W et al. (2009) Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial. Pediatrics 124:226-33
Conklin, Heather M; Khan, Raja B; Reddick, Wilburn E et al. (2007) Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial. J Pediatr Psychol 32:1127-39
Helton, Susan C; Corwyn, Robert F; Bonner, Melanie J et al. (2006) Factor analysis and validity of the Conners Parent and Teacher Rating Scales in childhood cancer survivors. J Pediatr Psychol 31:200-8

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