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Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.

ABSTRACT: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored.Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores.Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; -0.190 patients/Gy/year; P=.001), math (-0.164 patients/Gy/year; P=.010), reading (-0.137 patients/Gy/year; P=.011), and spelling scores (-0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (-0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (-0.150 patients/Gy/year; P=.002), math (-0.120 patients/Gy/year; P=.023), reading (-0.111 patients/Gy/year; P=.012), and spelling (-0.117 patients/Gy/year; P=.015) scores.Sparing portions of the cerebellum should be considered in RT planning for children with infratentorial ependymoma because of the potential impact of radiation dose on cognitive function.

SUBMITTER: Merchant TE

PROVIDER: S-EPMC4705097 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.

Merchant Thomas E TE Sharma Shelly S Xiong Xiaoping X Wu Shengjie S Conklin Heather H

International journal of radiation oncology, biology, physics 20140819 3

<h4>Purpose</h4>Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored.<h4>Methods and materials</h4>Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescr ...[more]

PMID: 25149660

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Project description:Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors.The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR.Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses.Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.

Dataset Information

Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.

Publications

Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.

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