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Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.

ABSTRACT: The purposes of this study were to determine the incidence of neurovascular events as late complications in pediatric patients with brain tumor and to evaluate radiation as a risk factor.Patients were ascertained using the tumor database of a pediatric tertiary care center. Included patients had a primary brain tumor, age birth to 21 years, initial treatment January 1, 1993, to December 31, 2002, and at least 2 visits with neuro-oncology. Radiation exposure included: whole brain, whole brain plus a focal boost, or focal brain. The primary outcome was stroke or transient ischemic attack.Of 431 subjects, 14 had 19 events of stroke or transient ischemic attack over a median follow-up of 6.3 years. The incidence rate was 548/100 000 person-years. Overall, 61.5% of subjects received radiation, including 13 of 14 subjects with events. Median time from first radiation to first event was 4.9 years. The stroke/transient ischemic attack hazard ratio for any brain irradiation was 8.0 (95% CI, 1.05-62; P=0.045); for the circle of Willis, radiation was 9.0 (95% CI, 1.2-70; P=0.035); and for focal noncircle of Willis, radiation was 3.4 (95% CI, 0.21-55; P=0.38).The incidence of neurovascular events in this population is 100-fold higher than in the general pediatric population and cranial irradiation is an important risk factor. By defining the incidence of this late effect, physicians are better able to counsel parents regarding treatment, monitor patients at risk, and target a population for primary stroke prevention in future studies.

SUBMITTER: Campen CJ

PROVIDER: S-EPMC3492057 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.

Campen Cynthia J CJ Kranick Sarah M SM Kasner Scott E SE Kessler Sudha K SK Zimmerman Robert A RA Lustig Robert R Phillips Peter C PC Storm Phillip B PB Smith Sabrina E SE Ichord Rebecca R Fisher Michael J MJ

Stroke 20120911 11

<h4>Background and purpose</h4>The purposes of this study were to determine the incidence of neurovascular events as late complications in pediatric patients with brain tumor and to evaluate radiation as a risk factor.<h4>Methods</h4>Patients were ascertained using the tumor database of a pediatric tertiary care center. Included patients had a primary brain tumor, age birth to 21 years, initial treatment January 1, 1993, to December 31, 2002, and at least 2 visits with neuro-oncology. Radiation ...[more]

PMID: 22968468

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Project description:IntroductionThis systematic review aims to elucidate the diagnostic accuracy of radiological examinations to distinguish between brain radiation necrosis (BRN) and tumor progression (TP).MethodsWe divided diagnostic approaches into two categories as follows-conventional radiological imaging [computed tomography (CT) and magnetic resonance imaging (MRI): review question (RQ) 1] and nuclear medicine studies [single photon emission CT (SPECT) and positron emission tomography (PET): RQ2]-and queried. Our librarians conducted a comprehensive systematic search on PubMed, the Cochrane Library, and the Japan Medical Abstracts Society up to March 2015. We estimated summary statistics using the bivariate random effects model and performed subanalysis by dividing into tumor types-gliomas and metastatic brain tumors.ResultsOf 188 and 239 records extracted from the database, we included 20 and 26 studies in the analysis for RQ1 and RQ2, respectively. In RQ1, we used gadolinium (Gd)-enhanced MRI, diffusion-weighted image, MR spectroscopy, and perfusion CT/MRI to diagnose BRN in RQ1. In RQ2, 201Tl-, 99mTc-MIBI-, and 99mTc-GHA-SPECT, and 18F-FDG-, 11C-MET-, 18F-FET-, and 18F-BPA-PET were used. In meta-analysis, Gd-enhanced MRI exhibited the lowest sensitivity [63%; 95% confidence interval (CI): 28-89%] and diagnostic odds ratio (DOR), and combined multiple imaging studies displayed the highest sensitivity (96%; 95% CI: 83-99%) and DOR among all imaging studies. In subanalysis for gliomas, Gd-enhanced MRI and 18F-FDG-PET revealed low DOR. Conversely, we observed no difference in DOR among radiological imaging in metastatic brain tumors. However, diagnostic parameters and study subjects often differed among the same imaging studies. All studies enrolled a small number of patients, and only 10 were prospective studies without randomization.ConclusionsDifferentiating BRN from TP using Gd-enhanced MRI and 18F-FDG-PET is challenging for patients with glioma. Conversely, BRN could be diagnosed by any radiological imaging in metastatic brain tumors. This review suggests that combined multiparametric imaging, including lesional metabolism and blood flow, could enhance diagnostic accuracy, compared with a single imaging study. Nevertheless, a substantial risk of bias and indirectness of reviewed studies hindered drawing firm conclusion about the best imaging technique for diagnosing BRN.

Project description:IntroductionCranial irradiation (IR) negatively regulates hippocampal neurogenesis and causes cognitive dysfunctions in cancer survivors, especially in pediatric patients. IR decreases proliferation of neural stem/progenitor cells (NSPC) and consequently diminishes production of new hippocampal neurons. Memantine, an NMDA receptor antagonist, used clinically to improve cognition in patients suffering from Alzheimer's disease and dementia. In animal models, memantine acts as a potent enhancer of hippocampal neurogenesis. Memantine was recently proposed as an intervention to improve cognitive impairments occurring after radiotherapy and is currently under investigation in a number of clinical trials, including pediatric patients. To date, preclinical studies investigating the mechanisms underpinning how memantine improves cognition after IR remain limited, especially in the young, developing brain. Here, we investigated whether memantine could restore proliferation in the subgranular zone (SGZ) or rescue the reduction in the number of hippocampal young neurons after IR in the juvenile mouse brain.MethodsMice were whole-brain irradiated with 6 Gy on postnatal day 20 (P20) and subjected to acute or long-term treatment with memantine. Proliferation in the SGZ and the number of young neurons were further evaluated after the treatment. We also measured the levels of neurotrophins associated with memantine improved neural plasticity, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).ResultsWe show that acute intraperitoneal treatment with a high, non-clinically used, dose of memantine (50 mg/kg) increased the number of proliferating cells in the intact brain by 72% and prevented 23% of IR-induced decrease in proliferation. Long-term treatment with 10 mg/kg/day of memantine, equivalent to the clinically used dose, did not impact proliferation, neither in the intact brain, nor after IR, but significantly increased the number of young neurons (doublecortin expressing cells) with radial dendrites (29% in sham controls and 156% after IR) and enhanced their dendritic arborization. Finally, we found that long-term treatment with 10 mg/kg/day memantine did not affect the levels of BDNF, but significantly reduced the levels of NGF by 40%.ConclusionThese data suggest that the enhanced dendritic complexity of the hippocampal young neurons after treatment with memantine may contribute to the observed improved cognition in patients treated with cranial radiotherapy.

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Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.

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Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.

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