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Late Effects

Central Nervous System




Many studies have shown that children treated for brain tumors develop intellectual decline which is progressive over at least a decade.

Radiation therapy (RT) and young patient age at the time of therapy are the most important risk factors for treatment induced cognitive decline.


Domains of neurobehavioral dysfunction in survivors of childhood cancer:



Intelligence Basic reasoning ability
Processing speed Rate of mental processing
Academic achievement School performance
Attention/concentration/distractibility Ability to focus on task for appropriate amount of time
Executive function Ability to plan, and organize information
Language Expressive and receptive language
Visuo-perceptual Ability to understand the position of objects in space
Fine motor Small, fine movements
Visuo-motor Ability to copy what you see using fine motor skills (eg. legible handwriting)
Memory Ability to learn and store new information and retrieve that information upon request
Adaptive function Functions of daily living, social skills and communication with others
Emotional and behavioral function Regulation of emotions, mood and behavior


Many factors contribute to long term neurocognitive problems in survivors of childhood cancer:

Tumor factors:

Children with leukemia are at risk for damage both from chemotherapy (methotrexate) and radiation therapy (RT).

Children with brain tumors are at even greater risk.  The magnitude of risk depends on location and extent of underlying tumor (treatment of supratentorial brain is more likely to lead to neurocognitive problems than treatment of the infratentorial brain).

Tumors may be associated with structural damage and  hydrocephalus which can contribute to generalized brain damage. However, there is little evidence from studies to show that the effect of hydrocephalus is significant.


Treatment factors

  • Radiation therapy (RT)
    • Dose dependent
    • Most damage is seen after high dose therapy to a large volume of supratentorial brain
    • Fractionation schedule (damage to normal tissues increased with large fraction size)
  • Chemotherapy
    • Concurrent chemotherapy sensitizes normal tissues
  • Surgery
    • Complications such as infection


Patient factors

  • Age
    • Younger children are at higher risk
  • Gender
    • Girls appear to be more vulnerable
  • Genetic
    • Some patients have underlying genetic problems such as ataxia-telangiectasia which makes it harder to repair radiation induced damage to DNA.


Denmark study9 assessing 133 consecutive pediatric brain tumor (PBT) patients:

  • 76 had RT
  • All had a brain tumor diagnosed < 15 years age
  • Treated between Jan 1970 & February 1997
  • 127 patients were able to cooperate  WISC-R and WAIS-R
  • 6 patients were too developmentally delayed for testing


  • Mean IQ scores substantially lower than expected
  • Significant predictors of lower cognitive function:
    • RT (most significant)
    • Younger age at diagnosis
    • Cerebral hemisphere tumor
    • Hydrocephalus treated with shunt

Mean observed full scale IQ:

  • Patients who did not have RT = 97.1
  • Patients given RT = 78.8


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