1.childpsych - pediatris brain tumors

Professional Background

• Presenter: Taryn Fay-McClymont, PhD, R.Psych.
    - Profession: Pediatric Neuropsychologist/ Clinical Child Psychologist
    - Position: Adjunct Professor, Department of Psychology, University of British Columbia (UBC) Okanagan

Pediatric Brain Tumors (PBT)

• Definition: Pediatric Brain Tumors are highly diverse in their histology, location, response to treatment, and survival rates.
• Current Advances:
    - Histology improvements
    - Identification enhancement
    - Advanced imaging techniques
    - Enhanced disease staging
    - Genetic understanding
• Survivorship:
    - PBT survivors have the highest cumulative burden of chronic health conditions of any cancer grade (St. Jude Lifetime Cohort Study, 2017).
• Neuropsychological Outcome:
    - PBT survivors exhibit a wide range of neurocognitive outcomes which are heterogeneous and influenced by various factors including:
      - Age at diagnosis
      - Presence of hydrocephalus/shunts
      - Stroke/complications from neurosurgery
      - Posterior Fossa Syndrome
      - Radiation Therapy
      - Chemotherapy-induced neuropathy
      - Sensorineural Hearing Loss/Vision Loss
      - Neuroendocrine dysfunction
      - Seizures
      - Time since diagnosis/therapy

Child Factors Influencing Neurocognitive Outcomes

• Factors:
    - Age at Diagnosis: Affects cognitive outcomes depending on developmental stages.
    - Pre-existing Conditions:
      - Medical/genetic conditions
      - Cognitive difficulties
      - Mental health concerns
    - Cognitive Resilience:
      - Cognitive Reserve
      - Emotional Resilience
    - Family Factors:
      - Parent’s mental health
      - Family stressors such as financial burden
      - Availability of psychosocial support and sibling relationships
    - Academic Factors:
      - Absence from school and late effects upon return
      - Academic achievement and emotional well-being

Direct Impact of Factors on Neurocognitive Outcomes

• Cancer Diagnosis Impact: Detrimental effects of cancer diagnosis on brain development.
• Treatment Factors:
    - Tumor Location: Affects surgical and subsequent treatment outcomes.
    - Surgery: Post-operative complications can lead to significant cognitive deficits.
    - Radiation Therapy:
      - Dosage and location are critical in determining outcomes.
    - Chemotherapy: Type, duration, and response vary greatly among patients.
    - Co-morbid illnesses: Influence overall neurocognitive capabilities.

White Matter Injury and Neurocognitive Outcomes

• Common Deficits: The most prevalent neurocognitive deficits in PBT survivors are linked to white matter injury (WMI).
• Causes of WMI:
    - Due to the disease process
    - Neurosurgical interventions
    - Cranial radiation therapy
    - Chemotherapy
• Consequences of White Matter Damage:
    - Direct loss or degeneration of white matter
    - Disruption of normal myelination along cortical white matter tracts
    - Delays in maturation of white matter
    - Interference with cerebellar functionality and connectivity
    - Decreased neurogenesis

Cranial Radiation Therapy (CRT)

• Linked Outcomes: Cranial radiation in PBT cases correlates with loss of white matter specifically in frontal lobes and various cortical areas.
• Dosage Correlation: There is a direct correlation between the amount of tissue radiated and neurocognitive late effects; the risk increases with higher doses and younger age.
• Radiation Therapy Impact: Radiotherapy contributes significantly to variance in neurobehavioral and IQ outcomes among PBT survivors.
    - WMI and Processing Speed Index (PSI) deficits account for a large portion of IQ variance.

Recent Developments in Radiation Therapy

• Proton vs. Photon Radiation Therapy:
    - Recent findings indicate that proton beam therapy may have promising cognitive outcomes by mitigating typical declines seen in photon therapy.
• Standard Therapy Protocols: Until recently, standard medulloblastoma therapy involved 5,400 cGy (54Gy) to the posterior fossa and 3,600 cGy to the neuroaxis.
    - Shift towards reduced dose protocols (e.g., 24Gy) is ongoing, with a focus on safer interventions.
• Technological Advances: Innovations in radiation therapy planning and delivery lead to lesser exposure of normal tissues and thus improvements in long-term cognitive toxicity outcomes.

Medulloblastoma: Epidemiology and Classification

• Incidence: Accounts for 30% of all pediatric CNS cancers; most common in children under 10 years old.
• Survival Rates:
    - Average survival rate is around 70%. Survivors often face quality of life challenges.
• Molecular Subtypes: Classification includes variants with distinct survival rates, highlighting the importance of genetic profile in prognosis.
• Histological Groups:
    - WNT, SHH, Group 3, Group 4, each with unique gene expression profiles, indicating distinct biological behaviors and outcomes.

Neuropsychological Functioning and Memory

• Role of the Hippocampus: Serves as the central hub for memory; radiation to the hippocampus correlates with declines in memory function.
• Recent Findings:
    - Goda et al. (2020) observed a 10-point decline in mean Full Scale IQ (FSIQ) scores for PBT patients receiving over 30 Gy to the left hippocampus.
• Impact of Complications: Hydrocephalus and VP shunts greatly affect memory performance, as shown in studies by Tsang (2020) and Acharya (2019).

Comparison of PBT and Acute Lymphoblastic Leukemia (ALL) Patients

• Overall IQ Performance:
    - No significant differences in FSIQ between PBT (n=33, Mean=90.94, SD=17.3) and ALL (n=39, Mean=94.18, SD=15) groups, Age=11.4 years.
• Clinical Impairment Rates:
    - PBT survivors display much higher rates of impairment across various memory types, including immediate and delayed verbal memory compared to ALL survivors.
• Statistical Outcomes:
    - Verbal Memory Index for PBT: Mean=91.64, SD=25 versus ALL: Mean=106.8, SD=14.4 (p=.008).

Educational Difficulties and Risk Factors

• High-Risk Groups include children and teens with:
    - Hearing loss
    - Posterior Fossa Syndrome
    - Surgical complications such as stroke
    - History of high-dose radiation therapy
    - Intrathecal therapy
• Common Neuropsychological Deficits:
    - Executive functioning issues, processing speed, working memory challenges, and fine motor dexterity impairment are prevalent in PBT survivors.

Long-Term Consequences of Neurocognitive Impairment

• Impacts:
    - Increased reliance on special education services
    - Reduced academic achievements and likelihood of attending higher education
    - Consequences for employability and independent living
    - Lower overall quality of life and reduced rates of marriage

Recommendations and Interventions

• Assessment Tools: Regular neuropsychological and psychoeducational assessments are crucial for identifying needs.
• Individualized Program Plan (IPP): Recommended strategies include:
    - Optimal classroom seating arrangements
    - Reducing written work and utilizing speech-to-text technologies
    - Providing handouts to minimize reliance on note-taking
    - Allowing extra time for tests,
      - Modifications for medical appointments to facilitate learning continuity
    - Offering remedial and small group instruction
• Additional Support:
    - Tutoring
    - Consultations for medication
    - Online learning resources
• Next Steps in Treatment:
    - Focus on hippocampal avoidance during therapies
    - Explore medications to moderate cognitive impacts
    - Enhance support within school environments (IEP)
    - Improve access to multidisciplinary rehabilitation (PT/SLP/OT)
    - Increase availability of stimulant medications such as Vyvanse
    - Foster community tutoring initiatives
    - Encourage ongoing research in cognitive rehabilitation approaches
    - Implement a comprehensive longitudinal approach to track cognitive function over time.

Case Study: Medulloblastoma Patient

• Demographics: 4-year-old girl presenting with headache, nausea, vomiting, dizziness, vertigo, and ataxia.
• Treatment: Following diagnosis, the patient underwent surgery, chemotherapy, and radiation therapy.

Posterior Fossa Syndrome (PFS)

• Definition: A collection of symptoms following cerebellar surgery, reported in up to 30% of children undergoing such operations.
• Symptoms:
    - Speech and communication deficits
    - Ataxia and balance issues
    - Cognitive declines leading to lowered IQ scores that may drop to intellectual disability ranges.

Dysembryoplastic Neuroepithelial Tumors (DNET)

• Characteristics:
    - WHO Grade 1 tumors, non-cancerous and slow-growing.
    - Comprised of glial and neuronal cells, often located in temporal lobe cortical gray matter (84% cases).
• Associated Conditions:
    - Commonly leads to seizures and drug-resistant epilepsy, yet many patients exhibit normal neurological status and IQ.

Post-Surgical Neuropsychological Outcomes of DNET

• Neuropsychological Measures:
    - A comparison of pre- and post-surgical performance:
      - Some domains showed decline while others indicated improvement in cognitive measures, particularly in Memory (CVLT-C and CMS) and working memory performance indicators.