Neuropsychological Outcomes in Childhood Cancer PowerPoint Presentation

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Neuropsychological Outcomes in Childhood Cancer and its Treatment Mikaela K. Sebree, Ph.D. Children’s Neuropsychology Program St. Luke’s Children’s Hospital

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Outline Common pediatric malignancies ALL Brain Tumors Neurocognitive late effects Model for understanding late effects Management of neurocognitive late effects

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Incidence of Pediatric Malignancies

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Acute Lymphoblastic Leukemia (ALL) Malignant disorder of lymphoid cells As recently as the 1960’s ALL was nearly always fatal Treatment for ALL Intrathecal (IT) and systemic chemotherapy Cranial radiation therapy (CRT) Treatment phases: Induction CNS prophylaxis and intensification Continuation

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Brain Tumors

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Supratentorial Tentorium Infratentorial

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Classification of Brain Tumors Astrocytoma – high grade and low grade Medulloblastoma Crainopharyngioma Brain Stem Glioma Ependyomomas Oligodendrogliomas

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Simple Typology of Brain Tumors

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Histology of Pediatric Brain Tumors

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Pediatric Brain Tumors Pediatric 50% infratentorial CNS primary site Gliomas and many others Molecular aspects Survival rates Adult 90% cerebral cortex Metastatic Gliomas/meningiomas Different molecular profile/genetic markers Poorer survival

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Treatment of Brain Tumors Surgery Radiation Chemotherapy

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Oncology Treatment ALL Standard vs high risk Chemotherapy MTX Steroids Radiation Brain Tumor Surgery Radiation Cranial Craniospinal Chemotherapy MTX

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Cure Rates in Pediatric Oncology * Includes both benign and malignant brain tumors

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Neurobehavioral Late effects

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Neurobehavioral Late Effects Factors Involved in Outcome Child: Genetic Factors Age Gender Tumor type/ genetic profile Premorbid factors Direct CNS injury: Location Hydrocephalus Surgery Surgical complications Treatment: Radiation Chemotherapy Medical complications Associated issues: Loss of Schooling Psychological adjustment Socialization issues Family functioning DEVELOPMENT

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Developmental Context Two potential consequences of tx: Loss/regression in skill development Failure to acquire skills in age-appropriate manner

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“Typical” Development What changes with development?? New systems come “on-line” Increasing sophistication of brain systems More interaction among systems Systems that support a skill at one age may not be the same as later Increasing specificity and integration across development

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Academic stress points Kindergarten 1st grade 4th grade Middle school High School College learning to learn learning to read reading to learn learning to organize learning learning to read, organize, learn – on your own Doing it all on your own

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Neurobehavioral Late Effects Cognitive ability Memory Attention Executive Functioning Motor Skills Academic Functioning Psychosocial Functioning

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Late effects: Surgery

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Neurosurgery Neurologic/sensory deficits Endocrine dysfunction Changes in physical appearance Posterior fossa syndrome Neuropsychological deficits Attention, memory, processing speed Lateralized/localized deficits

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Posterior Fossa Syndrome Consists of mutism +/- ataxia, cranial nerve deficits, and labile affect Mutism and affective lability typically resolves in 4-8 weeks As many as 20-30% of children are affected

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PFS cont. Children who experience PFS demonstrate persistent difficulties with social withdrawal and emotional lability Increased problems with working memory and initiation Slow processing speed Lower IQ Presence of PFS may be an index of increased risk for neurobehavioral morbidity

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Late Effects:Chemotherapy and Radiation

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Intellectual Ability Effects are slow to emerge, manifest progressively over time CRT is associated with lower IQ Estimated decline of 17 pts Reduced rate of learning – acquisition of new information at 40% expectations Age and Dose effect Even reduced dose have significant effect

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Attention/Concentration Deficits common in both ALL & BT Impairments in selective attention, focusing, and shifting Increased susceptibility to distraction

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Executive Functioning Slower speed of processing Limited working memory capacity Poor initiation Problems with planning and organization Limited cognitive flexibility/shifting Reduced hypothesis generation & problem solving

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Nondominant Hemisphere Functions Decreased nonverbal intelligence Spatial ability Visual motor integration skills Susceptibility to distraction Poor math skills

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Memory Verbal vs. visual memory Encoding, storage, and retrieval Interaction with executive deficits Dose effect – greater doses of radiation associated with greater impairments

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Academic Functioning Loss of schooling Declines in reading, spelling, and math Math skills are particularly vulnerable 57% of children with BT have specific LD – higher incidence of math LD

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Neurobehavioral Late Effects Core Deficits Attention Working Memory Engagement Processing Speed Secondary Deficits Loss of Intellectual Functioning Academic Failure

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Conceptual Model Disease & Treatment Age of Patient/ Neuro-development Processing Speed Attention Working Memory Intellectual Outcome Academic Achievement

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Risk Factors for Deficits

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Neuropathology of Deficits Damage to cortical and subcortical white matter Demyelination Radiation necrosis of white matter Reduction in the normal-appearing white matter DTI – reduction in white matter integrity Relationship between white matter volume intellectual outcomes

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Management Neuropsychological Evaluation Individualized Education Plan (IEP)/504 Plans Stimulant medication Innovative technology!!! Reading Writing Executive Functions

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Reading Text to speech software Available on most e-readers www.simplyaudiobooks.com www.audible.com www.bookshare.org Recording for the Blind and Dyslexic www.Ldonline.org www.fcrr.org

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Writing Speech to Text software Dragon Natural Speaking Organization: www.Inspiration.com Grammar/Spelling www.goqsoftware.com Ghotit.com www.spellingcity.com – spelling and vocabulary building games

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Executive Functioning Google calendar iphone/ipad/android apps Livescribe.com lumosity.com funbrain.com Cogmed.com

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Executive Function Resources Smart but Scattered: The Revolutionary "Executive Skills" Approach to Helping Kids Reach Their Potential  Peg Dawson and Richard Guare Executive Skills in Children and Adolescents, Second Edition: A Practical Guide to Assessment and Intervention Peg Dawson and Richard Guare Late, Lost, and Unprepared: A Parents’ Guide to Helping Children with Executive Functioning Joyce Cooper-Kahn, Ph.D. and Laurie Dietzel, Ph.D. Promoting Executive Function in the Classroom (What Works for Special-Needs Learners) Lynn Meltzer Fostering Independent Learning: Practical Strategies to Promote Student Success Virginia Smith Harvey Organizing the Disorganized Child: Simple Strategies to Succeed in School Martin L. Kutscher

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Summary Survivors are a population “at risk” Increasing impact of neuropsychological compromise over time Considerable neuropsychological morbidity Need for intervention and innovative approaches Major issue of transition to adulthood Highlights need to long term follow-up and comprehensive, multidisciplinary care

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Questions??? Hook ‘em Horns