Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer Journal Article


Authors: Butler, R. W.; Hill, J. M.; Steinherz, P. G.; Meyers, P. A.; Finlay, J. L.
Article Title: Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer
Abstract: Purpose: To investigate the neuropsychologic effects of cranial irradiation (CRT), intrathecal methotrexate (IT-MTX), and systemic methotrexate (SYS-MTX) in a cohort of pediatric patients with cancer who had either received no, moderate, or high doses of these treatments alone or in various combinations. Patient and Methods: Data were collected on 120 pediatric cancer patients from a large variety of diagnostic groups. Patients completed a comprehensive neuropsychologic test battery designed to assess most areas of cognitive functioning. In analyzing cancer treatment effects, the following variables were statistically controlled: (1) age, (2) socioeconomic status (SES), (3) age at diagnosis, (4) months since both onset and cessation of CNS treatments, (5) time missed from schooling, and (6) presence/type of CNS cancer. Results: CRT, largely in combination with IT- MTX, was significantly associated with deficits in several, primarily nondominant, hemispheric neuropsychologic functions, even after control and other treatment variables were addressed. This relationship was somewhat, but not highly, dose-dependent at CRT doses greater than approximately 18 Gy, at least over the first several years posttreatment. While there was statistically significant evidence for cognitive impairment, absence from school during treatment and age at diagnosis were more predictive of reading and spelling academic achievement than having received CRT. IT-MTX and SYS- MTX alone were not associated with significant degrees of neuropsychologic involvement. Conclusion: CRT, especially when administered with IT-MTX, at currently used dosages was associated with significant neuropsychologic impairment in children. These impairments are most likely to be reflected in non-verbal intelligence, perceptual abilities, and susceptibility to distraction. IT-MTX and SYS-MTX did not result in a consistent pattern of cognitive deficit.
Keywords: child; major clinical study; dose response; methotrexate; childhood cancer; skull irradiation; statistical analysis; cognition; drug blood level; reading; neuropsychology; intelligence; human; priority journal; article; perceptive discrimination; intrathecal drug administration
Journal Title: Journal of Clinical Oncology
Volume: 12
Issue: 12
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1994-12-01
Start Page: 2621
End Page: 2629
Language: English
DOI: 10.1200/jco.1994.12.12.2621
PROVIDER: scopus
PUBMED: 7989937
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Peter G Steinherz
    169 Steinherz
  2. Paul Meyers
    247 Meyers
  3. Jonathan Finlay
    62 Finlay