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Neuropsychological Outcomes in Childhood Cancer and its Treatment

Neuropsychological Outcomes in Childhood Cancer and its Treatment. Mikaela K. Sebree, Ph.D. Children’s Neuropsychology Program St. Luke’s Children’s Hospital. Outline. Common pediatric malignancies ALL Brain Tumors Neurocognitive late effects Model for understanding late effects

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Neuropsychological Outcomes in Childhood Cancer and its Treatment

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

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

  3. Incidence of Pediatric Malignancies

  4. 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

  5. Brain Tumors

  6. Supratentorial Tentorium Infratentorial

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

  8. Simple Typology of Brain Tumors

  9. Histology of Pediatric Brain Tumors

  10. 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

  11. Treatment of Brain Tumors Surgery Radiation Chemotherapy

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

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

  14. Neurobehavioral Late effects

  15. 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

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

  17. “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

  18. 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

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

  20. Late effects: Surgery

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

  22. 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

  23. 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

  24. Late Effects:Chemotherapy and Radiation

  25. 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

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

  27. 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

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

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

  30. 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

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

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

  33. Risk Factors for Deficits

  34. 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

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

  36. 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

  37. 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

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

  39. 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: AParents’ 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

  40. 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

  41. Questions??? Hook ‘em Horns

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