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Background: Posterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long‐term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years. Methods: Demographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome‐wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3). Results: A total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10‐year progression‐free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%‐53.1%). Analysis of consecutive 10‐year epochs revealed significant improvements in progression‐free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full‐scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (‐1.33 ± 0.42 points/year; P = .0042). Conclusions: Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time. In a subgroup‐specific manner, the results of the current study demonstrate that survival among patients with posterior fossa ependymoma has improved over time, and this improvement clearly is related to a change in practice with regard to pursuing aggressive surgical resections with upfront postoperative radiotherapy in all patients. This significant improvement highlights an urgent need for the implementation of early intervention and neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Background: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.Methods: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.Results: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.Conclusions: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. [ABSTRACT FROM AUTHOR]

The article offers information on several people who served at the Hospital for Sick Children in Toronto, Ontario. It mentions that the neurosurgery service of the hospital begun with the appointment of neurosurgeon William S. Keith in 1933. It says that E. Bruce Hendrick joined Keith in 1954 after he had obtained an specialty training in pediatric neurosurgery in Boston, Massachusetts. It states that Harold J. Hoffman was appointed as neurosurgical staff at Sick Kids in 1964.

Background: Identification of robust biomarkers of malignancy and methods to establish disease progression is a major goal in paediatric neuro-oncology. We investigated whether methylation of the TERT promoter can be a biomarker for malignancy and patient outcome in paediatric brain tumours., Methods: For the discovery cohort, we used samples obtained from patients with paediatric brain tumours and individuals with normal brain tissues stored at the German Cancer Research Center (Heidelberg, Germany). We used methylation arrays for genome-wide assessment of DNA. For the validation cohort, we used samples obtained from several tissues for which full clinical and follow-up data were available from two hospitals in Toronto (ON, Canada). We did methylation analysis using quantitative Sequenom and pyrosequencing of an identified region of the TERT promoter. We assessed TERT expression by real-time PCR. To establish whether the biomarker could be used to assess and predict progression, we analysed methylation in paired samples of tumours that transformed from low to high grade and from localised to metastatic, and in choroid plexus tumours of different grades. Finally, we investigated overall survival in patients with posterior fossa ependymomas in which the identified region was hypermethylated or not. All individuals responsible for assays were masked to the outcome of the patients., Findings: Analysis of 280 samples in the discovery cohort identified one CpG site (cg11625005) in which 78 (99%) of 79 samples from normal brain tissues and low-grade tumours were not hypermethylated, but 145 (72%) of 201 samples from malignant tumours were hypermethylated (>15% methylated; p<0.0001). Analysis of 68 samples in the validation cohort identified a subset of five CpG sites (henceforth, upstream of the transcription start site [UTSS]) that was hypermethylated in all malignant paediatric brain tumours that expressed TERT but not in normal tissues that did not express TERT (p<0.0001). UTSS had a positive predictive value of 1.00 (95% CI 0.95-1.00) and a negative predictive value of 0.95 (0.87-0.99). In two paired samples of paediatric gliomas, UTSS methylation increased during transformation from low to high grade; it also increased in two paired samples that progressed from localised to metastatic disease. Two of eight atypical papillomas that had high UTSS methylation progressed to carcinomas, while the other six assessed did not progress or require additional treatment. 5-year overall survival was 51% (95% CI 31-71) for 25 patients with hypermethylated UTSS posterior fossa ependymomas and 95% (86-100) for 20 with non-hypermethylated tumours (p=0.0008). 5-year progression-free survival was 86% (68-100) for the 25 patients with non-hypermethylated UTSS tumours and 30% (10-50) for those with hypermethylated tumours (p=0.0008)., Interpretation: Hypermethylation of the UTSS region in the TERT promoter is associated with TERT expression in cancers. In paediatric brain tumours, UTSS hypermethylation is associated with tumour progression and poor prognosis. This region is easy to amplify, and the assay to establish hypermethylation can be done on most tissues in most clinical laboratories. Therefore the UTSS region is a potentially accessible biomarker for various cancers., Funding: The Canadian Institute of Health Research and the Terry Fox Foundation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Pediatric brainstem tumors (BST) comprise a heterogeneous group of entities. Data regarding treatment options and outcome of BST, specifically brainstem low grade tumors (BSLGT) are limited. In order to better define risk groups and evaluate treatment options for pediatric BST, we performed a comprehensive analysis of all BST patients treated in our hospital during the MRI era., Procedures: We retrospectively analyzed clinical, imaging, and pathology data at presentation, treatment, and outcome of all BST patients followed at the Hospital for Sick Children in Toronto over the last 25 years., Results: Of 1,801 children with brain tumors, 223 (12%) had a brainstem primary location. Tumors without pontine involvement were BSLGT in 98.3%, whereas 75% of tumors involving the pons were high grade (P = 0.0001). Patients with BSLGT had 5-year progression-free survival (PFS) and overall survival (OS) of 57 ± 3% and 89 ± 5%, respectively. Upfront observation of tumor residual conferred no survival disadvantage with 5-year PFS and OS of 57 ± 5% and 93 ± 3%, respectively. In the group of patients requiring further treatment, 5-year PFS and OS were comparable between chemotherapy and radiotherapy with 53 ± 12% and 93 ± 4% and 66 ± 11% and 83 ± 6%, respectively (P = 0.26 and 0.3, respectively)., Conclusion: BST without pontine involvement are almost invariably BSLGT. Children with BSLGT have an excellent outcome even with careful initial observation. No clear benefit was observed for radiotherapy over chemotherapy when adjuvant treatment was needed. A conservative approach may be warranted for children with non-pontine brainstem lesions., (Copyright © 2011 Wiley Periodicals, Inc.)

Object: Extraaxial infections of the CNS, including subdural empyema and epidural abscess, are rare but potentially life-threatening conditions. Symptoms are usually progressive, and early diagnosis is therefore important. Early intervention with appropriate treatment offers the best opportunity for eradicating the infection and promoting maximal neurological recovery., Methods: The medical records of children with extraaxial CNS infection over the last 24 years at the Hospital for Sick Children were analyzed. Only those patients with radiological and/or operative confirmation of the diagnosis of subdural empyema or epidural abscess were included in the study. Demographic and clinical data were collected to determine the outcomes after such infections and factors that predict for such outcomes., Results: The authors identified 70 children who fulfilled the inclusion criteria. Sinusitis was the most common etiology and was seen in 38 patients. All of these patients were older than 7 years of age at diagnosis. Subdural empyemas were diagnosed in 13 patients following bacterial meningitis, and they were found primarily in infants within the 1st year of life. Other etiological factors included otogenic infection (4 cases), postneurosurgical infection (7 cases), and hematogenous spread of infection (7 cases including 6 cases of spinal epidural abscess). Streptococcus anginosus and Staphylococcus aureus were the most common pathogens identified. Sixty-four patients (91.4%) underwent at least 1 neurosurgical procedure. Seizures and cerebral edema from cortical vein thrombosis were the most common complications., Conclusions: Due to variable etiology, identification of the responsible microorganism through neurosurgical drainage followed by long-term intravenous antibiotics remains the mainstay in treating extraaxial CNS infections. Optimal outcome is achieved with early diagnosis and therapy.