Working Memory Performance Among Childhood Brain Tumor Survivors

Study Overview
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Brief Summary
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Children treated with radiation therapy for brain tumors are at risk for cognitive problems. These problems have typically been demonstrated on global cognitive measures including measures of intellectual functioning (IQ). Identification of specific areas of impairment can assist in isolating vulnerable brain areas and developing targeted interventions. In this study, we assess brain tumor survivors, solid tumor controls and healthy sibling controls using measures of working memory (online maintenance and manipulation of information) in order to identify a specific cognitive process that may underlie the observed decline in IQ. We are also exploring relationships among working memory performance with IQ, clinical characteristics and a specific genetic factor of interest.

Detailed Description
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This is a cross-sectional controlled study of brain tumor survivors treated at St. Jude with conformal radiation therapy. Brain tumor survivors (n= 50, solid tumor survivors (n=40), and healthy sibling controls (n= 40) are evaluated once only with laboratory measures of cognitive skills (working memory, episodic memory and estimated IQ) and parental questionnaires (executive and adaptive functions). We also use buccal (cheek) swabs to gather samples for DNA extraction. We hypothesize: brain tumor survivors will perform significantly worse than solid tumor and healthy controls on measures of working memory, working memory will correlate significantly with IQ, working memory will be associated with parent report of executive functions and a specified genotype related to dopamine metabolism will be associated with working memory impairment.

Official Title
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Working Memory Performance Among Childhood Brain Tumor Survivors Treated With Conformal Radiation Therapy: A Pilot Study

Conditions
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Brain Tumors

Intervention / Treatment
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* Behavioral: Series of tests/questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Brain Tumor Patients Treated for a primary central nervous system (CNS) tumor with conformal radiation therapy and enrolled on the institutional protocol RT-1 Initiated radiation therapy at least 2 years prior to enrollment with no evidence of recurrent disease Age 8-18 years inclusive at the time of enrollment, with sampling to obtain a broad cross-section of participants in terms of age, tumor location and time since RT initiation English as the primary language Research participant and one parent willing to participate and provide consent/assent according to institutional guidelines Solid Tumor Patient Controls Treated for a solid tumor (i.e., Ewing's sarcoma, osteosarcoma, soft tissue/rhabdomyosarcoma, neuroblastoma or Wilms tumor) at St. Jude without CNS directed therapy - Diagnosed at least 2 years prior to enrollment Age 8-18 inclusive at the time of enrollment, with age, gender and race sampling to broadly match the brain tumor group English as the primary language Research participant and one parent willing to participate and provide consent/assent according to institutional guidelines Sibling Controls Healthy sibling controls- siblings of St. Jude patients treated for a brain tumor (not necessarily on RT-1) Age 8-18 inclusive, with age and gender sampling to broadly match the patient group English as a primary language Research participant and one parent willing to participate and provide consent/assent according to institutional guidelines Exclusion Criteria: Brain Tumor Patients Significant impairment in global intellectual functioning (operationalized as an estimated IQ less than 70 as indicated by most recent RT-1 testing) History of documented CNS injury or disease predating cancer diagnosis History of documented Attention Deficit Hyperactivity Disorder (ADHD) predating cancer diagnosis by at least one year (must have been diagnosed by a physician with medication prescribed) Treatment with psychostimulant or psychotropic medication within two weeks of study enrollment Sensory or motor impairment that would preclude valid cognitive testing Solid Tumor and Sibling Controls Significant impairment in global intellectual functioning (operationalized as a history of special education in a self-contained classroom) History of documented CNS injury or disease History of documented Attention Deficit Hyperactivity Disorder (ADHD) (must have been diagnosed by a physician with medication prescribed) Treatment with psychostimulant or psychotropic medication within two weeks of study enrollment Sensory or motor impairment that would preclude valid cognitive testing

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1: Brain Tumor Survivors (n=50)<br> | Behavioral: Series of tests/questionnaires<br>* Developmental and Demographic, KINDL Health-Related Quality of Life, Adaptive Behavior Assessment System (ABAS-II),Behavior Rating Inventory of Executive Function (BRIEF), Wechsler Digit Span Task, Wide Range Achievement Test 3rd Edition (WRAT3),Wechsler Abbreviated Scale of Intelligence (WASI), Pediatric Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Recognition Memory Task: Face Stimuli, Recognition Memory Task: Verbal Stimuli, Self Ordered Search: Object, Self Order Search: Verbal<br>|
| 2: Healthy Sibling Controls (n=40)<br> | Behavioral: Series of tests/questionnaires<br>* Developmental and Demographic, KINDL Health-Related Quality of Life, Adaptive Behavior Assessment System (ABAS-II),Behavior Rating Inventory of Executive Function (BRIEF), Wechsler Digit Span Task, Wide Range Achievement Test 3rd Edition (WRAT3),Wechsler Abbreviated Scale of Intelligence (WASI), Pediatric Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Recognition Memory Task: Face Stimuli, Recognition Memory Task: Verbal Stimuli, Self Ordered Search: Object, Self Order Search: Verbal<br>|
| Solid Tumor Survivors (n=40)<br> | Behavioral: Series of tests/questionnaires<br>* Developmental and Demographic, KINDL Health-Related Quality of Life, Adaptive Behavior Assessment System (ABAS-II),Behavior Rating Inventory of Executive Function (BRIEF), Wechsler Digit Span Task, Wide Range Achievement Test 3rd Edition (WRAT3),Wechsler Abbreviated Scale of Intelligence (WASI), Pediatric Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Recognition Memory Task: Face Stimuli, Recognition Memory Task: Verbal Stimuli, Self Ordered Search: Object, Self Order Search: Verbal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance on experimental working memory measures (computerized self-ordered pointing tasks) |  | Collected during one time cross-sectional assessment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abbreviated IQ (WASI), episodic memory measures (computerized word and face recognition tasks) and parent questionnaires of executive (BRIEF) and adaptive (ABAS-II) functioning. |  | Collected during one time cross-sectional assessment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Tumor, Cognitive Late Effects, Radiation Therapy, Working Memory