The investigators propose a multidisciplinary project to describe the frequency, nature, and longitudinal course of the effects of radiotherapy (RT) on cognition and cerebral white matter in adults with low-grade, supratentorial brain tumors. They have identified a neurobehavioral model of the early-delayed effects of radiotherapy, characterized by decrement and rebound of semantic memory retrieval. They will investigate the validity of these findings in brain tumor groups with and without radiotherapy. They will concurrently validate the model by comparing it with another cognitive memory model, and will identify the onset of other cognitive changes. The investigators plan to investigate dose-dependent effects of radiotherapy by relating neuropsychological measures to reconstructions of dose burden to hypothesized brain regions. They will also relate dose and neuropsychological outcome to serial magnetic resonance imaging (MRI). They will compare magnetization transfer imaging (MTI) with MRI and expect that MTI will show greater sensitivity and specificity to the late-delayed changes, will differentiate axonal degeneration from edema, and will show higher correlations with neuropsychological measures. Over the five years of the project, the investigators will recruit new patients with low-grade gliomas, pituitary and other low-grade tumors because of their long life expectancies. Patients with gliomas who did not receive radiotherapy will be also sought as a control group. They propose to recruit 220 new cases, and will follow 22 cases from their pilot study over the study period. Hypotheses about treatment effects will be tested using subjects as their own controls and treatment group comparisons. They will conduct neuropsychological evaluation (10 domains and mood/fatigue) at baseline (about 6 weeks post surgery and just prior to radiotherapy), 6 weeks post-completion of radiotherapy, trimonthly for one year, and then yearly. Cognitive neuropsychological models of memory search and retrieval over time will be investigated to discern the relation of neurocognitive impairment to brain structure. They will correlate cognitive variables with dose and graded MRI scans of all patients. Dose histograms will quantify dose to hypothesized brain structures and radiation portals. They will gather pilot data on the sensitivity of MTI to radiation effects in 37 cases during the early and late delayed periods. Standard brain regions, tumor sites and specific regions will be examined.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA065438-06
Application #
6376104
Study Section
Behavioral Medicine Study Section (BEM)
Program Officer
Stone, Helen B
Project Start
1997-06-01
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2004-07-31
Support Year
6
Fiscal Year
2001
Total Cost
$605,552
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Armstrong, Carol L; Shera, David M; Lustig, Robert A et al. (2012) Phase measurement of cognitive impairment specific to radiotherapy. Int J Radiat Oncol Biol Phys 83:e319-24
Seiler, Christie Burger; Jones, Kelly E; Shera, David et al. (2011) Brain region white matter associations with visual selective attention. Brain Imaging Behav 5:262-73
Niemitz, Emily L; Feinberg, Andrew P; Brandenburg, Sheri A et al. (2005) Children with idiopathic hemihypertrophy and beckwith-wiedemann syndrome have different constitutional epigenotypes associated with wilms tumor. Am J Hum Genet 77:887-91
Armstrong, Carol L; Traipe, Elfrides; Hunter, Jill V et al. (2004) Age-related, regional, hemispheric, and medial-lateral differences in myelin integrity in vivo in the normal adult brain. AJNR Am J Neuroradiol 25:977-84
Armstrong, Carol L; Gyato, Kunsang; Awadalla, Abdel W et al. (2004) A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy. Neuropsychol Rev 14:65-86
Goldstein, Bram; Armstrong, Carol L; Modestino, Edward et al. (2004) The impact of left and right intracranial tumors on picture and word recognition memory. Brain Cogn 54:1-6
Goldstein, Bram; Obrzut, John E; John, Cameron et al. (2004) The impact of frontal and non-frontal brain tumor lesions on Wisconsin Card Sorting Test performance. Brain Cogn 54:110-6
Goldstein, Bram; Obrzut, John E; John, Cameron et al. (2004) The impact of low-grade brain tumors on verbal fluency performance. J Clin Exp Neuropsychol 26:750-8
Goldstein, Bram; Armstrong, Carol L; John, Cameron et al. (2003) Attention in adult intracranial tumors patients. J Clin Exp Neuropsychol 25:66-78
Armstrong, Carol L; Goldstein, Bram; Shera, David et al. (2003) The predictive value of longitudinal neuropsychologic assessment in the early detection of brain tumor recurrence. Cancer 97:649-56

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