International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationInvestigating Verbal and Visual Auditory Learning After Conformal Radiation Therapy for Childhood Ependymoma
Introduction
Advances in conformal radiation therapy (CRT) have lowered the risk of cognitive decline in pediatric brain tumor patients by minimizing exposure of healthy brain tissue to irradiation 1, 2, 3, 4. CRT uses three-dimensional imaging and specialized software to concentrate the prescribed dose to the tumor while sparing surrounding healthy tissue (3). Research has linked higher doses of radiation to longitudinal decline in IQ, memory, attention, and academic achievement 2, 3, 4. These adverse effects are more pronounced with conventional radiation therapy compared with CRT 5, 6, 7, 8. Cognitive decline after irradiation has been attributed to a slower rate of knowledge acquisition vs. loss of intellectual skill 9, 10.
A prior study examining neurocognitive outcome in children with ependymoma treated with CRT found that children aged under 3 years at the time of CRT had significantly lower intellectual function scores at baseline compared with children over 3 years (3). However, these differences were no longer significant at the 48-month follow-up time point because the younger cohort exhibited an increase in IQ over time (3). No significant declines in memory, academic achievement, or adaptive behavior were found at the 24-month follow-up time point, although only a portion of the cohort completed all measures of memory, learning, and academic achievement (3).
CRT has demonstrated the potential to reduce global cognitive decline following treatment; however, the possibility of decline in other neurocognitive domains remains to be determined 2, 3, 11, 12, 13, 14, 15. Preliminary evidence of subtle difficulties in reading, attention, and memory following irradiation in the treatment of ependymoma have been reported 15, 16. We recently found that children with ependymoma experienced modest declines in reading, but not math or spelling, after CRT (16). Another study of children treated with conventional irradiation for infratentorial ependymoma revealed reading difficulties after treatment, as well as visuospatial, memory, and attention deficits, despite the lack of significant deterioration in aggregate IQ scores following treatment (15).
Childhood ependymoma typically emerges at an earlier age than other localized tumors such as craniopharyngioma and astrocytoma, which may create additional risk because young age is a robust predictor of adverse neurocognitive outcome 4, 17, 18, 19, 20, 21. Studies investigating outcome in children with ependymoma have found young age to predict lower mean scores on measures of intellectual function, although young age has not necessarily been found to predict decline in intellectual function after treatment 3, 8, 15.
For the current study, verbal and visual-auditory learning were serially assessed in children with localized ependymoma. Patients were treated with smaller-than-conventional volumes with the objective of sparing normal tissue. It was our hypothesis that the use of CRT would not result in significant longitudinal decline in verbal or visual-auditory learning after treatment. A secondary goal was to examine the effect of age and other select clinical factors on neurocognitive outcome. Despite advances in CRT, age was predicted to exert a modest but significant effect on rate of learning after treatment. Hypothetically, older children were expected to exhibit a more rapid rate of learning over time than younger children. To our knowledge, no prior studies have examined and compared rate of longitudinal verbal and visual-auditory learning in a prospective manner over a 5-year span. Recent advances in treatment have reduced the likelihood of more pervasive and conspicuous deficits in the form of global neurocognitive decline(s) after treatment 2, 3, 4, 5, 6, 7, 8, 9, 10. Therefore, future studies will need to adapt to treatment advances by using investigative methods that are more sensitive to the detection of specific and less conspicuous side effects. The investigative methods used in this study could serve as a potential benchmark for future studies.
Section snippets
Patients
Seventy-one pediatric patients with localized primary ependymoma were enrolled in a Phase II trial of CRT between July 1997 and August 2007. The study was approved by the institutional review board, and written informed consent was obtained before participation. Criteria for enrollment included diagnosis of localized ependymoma without metastasis, age range between 1 and 21 years at the time of irradiation, no prior irradiation, no ongoing chemotherapy, and adequate performance status (Eastern
Memory outcomes
Mean scores on the CVLT-C (43.78) and VAL (91.86) were in the average range at the start of CRT. There was no evidence of decrease in CVLT-C and VAL scores over time following CRT. In contrast, a trend for increase was found on the CVLT-C (.12 ± .041 points/month; p = 0.03) and a significant increase on the VAL (.20 ± .054 points/month; p = <0.01) over the 5-year follow-up time period.
Testing for practice effects
The results revealed no difference in the rate of improvement between those with more (>4) vs. fewer
Discussion
The results of this study support the primary hypothesis that patients with ependymoma treated with smaller-than-conventional volumes using CRT do not exhibit longitudinal decline in verbal or visual-auditory learning after treatment. These findings are notable because longitudinal declines in learning and intellectual functioning are associated with conventional radiation therapy 5, 6, 7, 8.
Evidence supporting the secondary hypothesis that older children would exhibit a more rapid rate of
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This work was supported in part by Cancer Center Support Grant No. CA21765 from the National Cancer Institute, by Research Project Grant No. RPG-99-252-01-CCE from the American Cancer Society, and by the American Lebanese Syrian Associated Charities (ALSAC).
Conflict of interest: none.