Elsevier

Current Problems in Cancer

Volume 27, Issue 4, July–August 2003, Pages 177-197
Current Problems in Cancer

Neurocognitive late effects in pediatric cancer

https://doi.org/10.1016/S0147-0272(03)00026-6Get rights and content

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Acute lymphoblastic leukemia

Approximately 20,000 children and adolescents under the age of 20 years were diagnosed with cancer in 1999.7 ALL accounts for one fourth of all childhood cancers and 78% of all cases of childhood leukemia.1 In the United States, approximately 3000 children are diagnosed with ALL each year, with an incidence of 3 to 4 cases per 100,000 white children. Central nervous system (CNS) preventive therapy is necessary because the CNS is a sanctuary for occult leukemia. Traditionally, CNS therapy has

Core and secondary symptoms of the neurocognitive phenotype

Deficits in broad-spectrum abilities measured by tests of academic achievement and intellectual functioning have been well documented in the literature. These symptoms can produce limitations in age-appropriate activities of daily living, such as school performance, employment, independent living, and quality of life among subsets of surviving patients.26, 27, 28 These problems were the first to be quantified in the neuro-oncology literature and remain important end points in any pediatric

Neuropathologic changes

Studies using neuroimaging have shown changes in brain tissue after chemotherapy and radiation treatment. By using computerized tomography to study patients with brain malignancies, several CNS abnormalities, such as cerebral atrophy, calcifications, focal and diffuse white matter lesions, and enlarged ventricles, have been qualitatively defined.38 Late effects of treatment-related CNS injury in ALL survivors include diffuse and multifocal white matter abnormalities, demyelination, breakdown of

Gender

The most convincing data relating to gender as a risk factor for increased neurotoxicity has come from the work of the Dana Farber group with patients treated for ALL,54, 55, 56 although this effect had been reported incidentally in other papers.10 When gender effects have been investigated and have had significant effects on cognitive function, female gender confers a greater risk. Waber’s initial study used a control group with solid tumors who had not received CNS therapy to assess the risks

Compensatory neurobiological systems

The concept of “brain reserve capacity” has been proposed by Satz to explain individual variation in the behavioral manifestation of signs and symptoms of brain damage.58 Using a model derived from adult studies of progressive neurologic diseases that result in dementia (Alzheimer’s disease, Parkinson’s disease, acquired immunodeficiency syndrome), he proposes that each individual has a unique threshold for tolerance of brain damage before signs and symptoms are noted. Cumulative effects of

Compensatory psychosocial systems

Although patients with varying types of CNS treatments may express similar core neurocognitive symptoms, considerable variability exists in their actual academic performance. Aside from treatment factors, one possible explanation is that the home, school, and community environments of patients have differences in their ability to compensate for core deficits and thus affect the intensity of secondary symptoms, such as achievement in school. For example, among healthy samples of children,

Interventions for neuropsychological deficits

Although research on the patterns and risks for neuropsychological and educational deficits among survivors of childhood cancer has been progressing for the past three decades, the development of empirically validated interventions for these deficits has not been as rapid. Broadly speaking, interventions can be divided into two approaches: those intended to avoid or reduce the neuropsychological toxicity of therapy directed toward the CNS, and those intended to minimize or rehabilitate deficits

Conclusion

In November 2000, a report from the Brain Tumor Progress Review Group, jointly sponsored by the National Cancer Institute and the National Institute for Neurological Disorders and Stroke, articulated four priority areas for pediatric research.66 Two of these related to the neurocognitive functioning of surviving children. In particular, an emphasis was placed on more accurate assessment of risks for deficits, the development of more precise methods of assessing functional and structural damage

Acknowledgment

Preparation of the article was supported in part by the American Lebanese Syrian Associated Charities and grants CA 21765 and CA 20180 from the National Cancer Institute. This article was commissioned by the National Cancer Policy Board of the Institute of Medicine, National Academy of Sciences.

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