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Background: Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort., Methods: All individuals younger than 18 years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5 years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared., Results: Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10 years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p = .0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p < .0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p < .0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p < .0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p < .0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p < .0001) compared to controls., Conclusions: Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objective: Query the National Cancer Database (NCDB) to delineate epidemiologic frequency, care patterns, and survival outcomes of pediatric intramedullary spinal cord tumors (IMSCTs)., Methods: IMSCTs included ependymoma, astrocytoma, and hemangioblastoma. We examined data from the NCDB spanning 2004-2018, focusing on IMSCT in children aged 0-21 years. Our analysis included logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models., Results: This study included 1066 patients aged 0-21 years. 59.4 % of patients were male, while 83.1 % were white. The most common tumor histology was ependymoma (57.5 %), followed by astrocytoma (36.1 %) and hemangioblastoma (6.4 %). 24.9 % of patients received radiotherapy, with radiotherapy utilization being highest among patients aged 6-10 years. Chemotherapy utilization was highest in patients aged 0-5 years. 87.2 % of patients underwent surgical resection, with higher rates in patients aged 16-21 years. Overall survival did not differ significantly between resected and non-resected patients (p = 0.315). Patients in rural areas had worse OS than those in metro areas (HR = 4.42, p = 0.048). Patients with astrocytoma had worse OS compared to other histologies (HR = 2.21, p = 0.003). Astrocytoma patients were over twice as likely to have prolonged LOS compared to ependymoma patients (OR = 2.204, p < 0.001)., Conclusions: In summary, our analysis utilizing the NCDB database provides a comprehensive overview of demographics, care patterns, and outcomes for the largest cohort of pediatric IMSCTs to date. These insights underscore the complexity of managing IMSCTs and emphasize the need for tailored approaches to improve patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Spinal intradural tumors are rare and heterogeneous in histological type, aggressiveness, and symptomatology, and there is a lack of data about them. This study investigated the epidemiological features of spinal intradural tumors., Methods: This retrospective analysis included patients with spinal intradural tumors who underwent surgical treatment at the Myelopathy and Spondylosis Ward Beijing Jishuitan Hospital between January 2012 and December 2022., Results: This study included 1321 patients [aged 47.19 ± 14.90 years, 603 (45.65%) males] with spinal intradural tumors. The most common histological subtype was schwannoma [n = 511 (38.68%)], followed by spinal meningioma [n = 184 (13.93%)] and ependymoma [n = 101 (7.65%)]. Fifteen (1.14%) patients were diagnosed with metastatic spinal intradural tumors as a presentation of another primary cancer type. The spinal intradural tumors were mostly found in the lumbar region [n = 436 (33.01%)], followed by the thoracic vertebrae [n = 390 (29.52%)], cervical vertebrae [n = 154 (11.66%)], and thoracolumbar region [n = 111 (8.40%)]. Schwannomas mostly affected the lumbar region [n = 256 (52.64%)], spinal meningiomas in the thoracic region [n = 153 (83.15)], and ependymomas in the lumbar region [56 (55.45%)]. The de novo metastases were mostly found in the lumbar region [n = 8 (53.33%)]., Conclusion: According to the results of our single-center study, the most common spinal intradural tumor in Northern China is schwannoma, followed by spinal meningioma and ependymoma., (© 2024. The Author(s).)

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Thus, we aimed to describe the frequency, incidence, and specific clinical and histological features of central nervous system (CNS) tumors in the MEN1 population (except pituitary tumors)., Experimental Design: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed up in the French MEN1 national cohort. The standardized incidence ratio (SIR) was calculated based on the French Gironde CNS Tumor Registry. Genomic analyses were performed on somatic DNA from seven CNS tumors, including meningiomas and ependymomas from patients with MEN1, and then on 50 sporadic meningiomas and ependymomas., Results: A total of 29 CNS tumors were found among the 1,498 symptomatic patients (2%; incidence = 47.4/100,000 person-years; SIR = 4.5), including 12 meningiomas (0.8%; incidence = 16.2/100,000; SIR = 2.5), 8 ependymomas (0.5%; incidence = 10.8/100,000; SIR = 17.6), 5 astrocytomas (0.3%; incidence = 6.7/100,000; SIR = 5.8), and 4 schwannomas (0.3%; incidence = 5.4/100,000; SIR = 12.7). Meningiomas in patients with MEN1 were benign, mostly meningothelial, with 11 years earlier onset compared with the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified as World Health Organization grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from patients with MEN1, whereas MEN1 deletion in one allele was present in 3/41 and 0/9 sporadic meningiomas and ependymomas, respectively., Conclusions: The incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas., (©2024 American Association for Cancer Research.)

Background: Spinal cord ependymomas (SCEs) represent the most common intramedullary spinal cord tumors among adults. Research shows that access to neurosurgical care and patient outcomes can be greatly influenced by patient location. This study investigates the association between the outcomes of patients with SCE in metropolitan and nonmetropolitan areas., Methods: Cases of SCE between 2004 and 2019 were identified within the Central Brain Tumor Registry of the United States, a combined dataset including the Centers for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results Program data. Multivariable logistic regression models were constructed to evaluate the association between urbanicity and SCE treatment, adjusted for age at diagnosis, sex, race and ethnicity. Survival data was available from 42 National Program of Cancer Registries (excluding Kansas and Minnesota, for which county data are unavailable), and Cox proportional hazard models were used to understand the effect of surgical treatment, county urbanicity, age at diagnosis, and the interaction effect between age at diagnosis and surgery, on the survival time of patients., Results: Overall, 7577 patients were identified, with 6454 (85%) residing in metropolitan and 1223 (15%) in nonmetropolitan counties. Metropolitan and nonmetropolitan counties had different age, sex, and race/ethnicity compositions; however, demographics were not associated with differences in the type of surgery received when stratified by urbanicity. Irrespective of metropolitan status, individuals who were American Indian/Alaska Native non-Hispanic and Hispanic (all races) were associated with reduced odds of receiving surgery. Individuals who were Black non-Hispanic and Hispanic were associated with increased odds of receiving comprehensive treatment. Diagnosis of SCE at later ages was linked with elevated mortality (hazard ratio = 4.85, P < 0.001). Gross total resection was associated with reduced risk of death (hazard ratio = 0.37, P = 0.004), and age did not interact with gross total resection to influence risk of death., Conclusions: The relationship between patients' residential location and access to neurosurgical care is critical to ensuring equitable distribution of care. This study represents an important step in delineating areas of existing disparities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence., Methods: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies., Results: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses., Conclusion: Our data suggest that breastfeeding does not protect against CBT., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To enumerate the burden of ependymoma in our region and identify the demographic, tumoural, surgical, clinical characteristics, and outcomes of patients diagnosed with ependymoma., Methods: This retrospective cross-sectional study included patients admitted under neurosurgical service between January 1 and December 31, 2019. The inclusion criterion for the study was a histopathological diagnosis of the brain lesion. The experience of the ependymal brain tumours observed at the 32 participating sites in Pakistan is presented., Results: A total of 2750 patients with brain tumours were seen in 2019 at our centres of whom 58(2.1%) had a histopathological diagnosis of ependymoma. The median age at diagnosis was nine (IQR= 4.5-24.5) years. The median time to surgery from date of radiological diagnosis was 38.5 (IQR= 4-93.8) days. The median KPS score at presentation was 70 (IQR= 60-80), and post-surgery was 90 (IQR= 70-100), showing an average increase of 20. Our population's overall mortality rate for ependymoma was 31.1%, with the 30-day mortality rate being 2.2% (lower than the 4.5% on average for all brain tumours in our cohort)., Conclusions: Ependymomas were predominantly found in the paediatric population in the presented cohort. While gender distribution and histopathological grading seemed to follow international trends, this study had a much higher mortality rate and a much lower gross total resection rate than centres in high-income countries.

Purpose: Evidence exists, in CNS germinomas and medulloblastomas (MB), that patient sex significantly influences incidence and outcome. The role of sex genotype in other paediatric CNS tumours remains unclear. This study sought to examine the role of sex genotype in CNS tumour incidence and overall survival (OS)., Methods: Age-adjusted incidence and OS rates were collected from the Surveillance Epidemiology and End Result (SEER) registry between 2000 and 2011 for common paediatric (<=19 years) CNS tumours: pilocytic astrocytoma (PA), anaplastic astrocytoma, glioblastoma (GBM), medulloblastoma, supratentorial CNS embryonal tumour, ependymoma, and germinoma. All patients with histologically confirmed, ICD-03 coded, first tumours, were included. Kaplan-Meier and Cox regression analyses were used to calculate hazard ratios (HR)., Results: The total cases are as follows: males=3018 and females=2276. Highest incidence was seen in PA (n=2103). GBM displayed the worst OS, whilst PA displayed the best. Higher incidence was observed in males for all tumours, except PA. Females with ependymoma had significantly better OS compared to males, whereas males with germinomas had better OS compared to females. Females <1 year with AA had better OS than males. Increasing age significantly improved male and female survival in ependymoma and medulloblastoma., Conclusion: Interrogating population-based registries such as SEER minimises bias and provides credible data. Observed differences in incidence and OS between the sexes for different paediatric CNS tumours provide useful prognostic information for clinicians. Sex genotype was a significant independent prognostic factor in ependymomas and germinomas. Further investigation of possible epigenetic and hormonal differences may provide sex-specific vulnerabilities that may be exploitable for targeted therapy.

Background: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations., Methods: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS)., Results: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients., Conclusions: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The number of children who were born after their parents were diagnosed with central nervous system (CNS) tumor is increasing, but it remains largely unknown regarding the academic performance of these children. We aimed to investigate whether children of survivors with childhood or adolescent CNS tumor were associated with poor academic performance. Children of survivors of CNS tumor were identified by combining the nationwide Swedish Cancer Register and the Multi-Generation Register, and those who have completed compulsory education in Sweden between 1989 and 2015 were included in our study. "Poor academic performance" was defined as a z-score of the academic performance below the 10th percentile. Conditional logistic regression and quantile regression were used to examine the association. A total of 655 children were born after their parental diagnosis of CNS tumor and they had 1.39 times higher risk of achieving poor academic performance as compared to the matched comparisons (95% CI = 1.10-1.76). The poor academic performance was even more pronounced in boys, among those with a paternal diagnosis of CNS tumor and those with a parental ependymoma. The observed association differed depending on preterm birth. In addition, the strength of the association declined with the increased quantiles of academic performance z-score. Our data suggest that parental CNS tumor affects the subsequent academic achievements among children born after the parental tumor., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. To investigate whether genetic predisposition to longer telomere length influences ependymoma risk, we utilized case-control data from three studies: a population-based pediatric and adolescent ependymoma case-control sample from California (153 cases, 696 controls), a hospital-based pediatric posterior fossa type A (EPN-PF-A) ependymoma case-control study from Toronto's Hospital for Sick Children and the Children's Hospital of Philadelphia (83 cases, 332 controls), and a multicenter adult-onset ependymoma case-control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). In the California case-control sample, a polygenic score for longer telomere length was significantly associated with increased risk of ependymoma diagnosed at ages 12-19 (P = 4.0 × 10 -3 ), but not with ependymoma in children under 12 years of age (P = 0.94). Mendelian randomization supported this observation, identifying a significant association between genetic predisposition to longer telomere length and increased risk of adolescent-onset ependymoma (OR PRS  = 1.67; 95% CI 1.18-2.37; P = 3.97 × 10 -3 ) and adult-onset ependymoma (P MR-Egger  = 0.042), but not with risk of ependymoma diagnosed before age 12 (OR = 1.12; 95% CI 0.94-1.34; P = 0.21), nor with EPN-PF-A (P MR-Egger  = 0.59). These findings complement emerging literature suggesting that augmented telomere maintenance is important in ependymoma pathogenesis and progression, and that longer telomere length is a risk factor for diverse nervous system malignancies.

Background: Ependymoma (EPN) is the third most common childhood cancer of the central nervous system. RELA fusion-positive EPN accounts for approximately 70% of all childhood supratentorial tumors and shows the worst prognosis among the supratentorial EPNs. TP53 mutation is infrequent in RELA fusions EPNs. In the population from the Southern region of Brazil, there is a high incidence of the germline TP53 p.R337H mutation that predisposes carriers to develop early-onset tumors. However, despite this high incidence, the frequency of this mutation among EPN patients remains to be determined. Here, we investigated the presence of the TP53 p.R337H mutation in a larger cohort of pediatric EPNs of three institutions located in the state of São Paulo, Brazil., Methods: The TP53 p.R337H mutation was screened by conventional RT-PCR and Sanger sequencing in 49 pediatric EPNs diagnosed during the period from 1995 to 2016., Results: We described for the first time a case of a 5-year-old girl with RELA fusion EPN with a heterozygous TP53 p.R337H mutation., Conclusions: The present finding indicates that the TP53 p.R337H germline mutation is uncommon in patients with EPN in Brazil and screening of pediatric patients RELA fusion EPN may be informative to better understand the role of TP53 germline mutations in the development and prognosis of these tumors.

Introduction: Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols., Methods: Tumor samples of 134 patients aged 0.2-15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis., Results: Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures., Conclusion: The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.

Purpose: The aim of this study was to identify racial/ethnic disparities with regard to survival among patients with ependymoma., Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registry between the years of 1973-2015 which included 4821 patients diagnosed with ependymoma were analyzed. Multivariable cox proportional hazard ratios were performed to examine overall survival across racial/ethnic groups of patients with ependymoma, mortality risks across specified age groups, and mortality during specified time intervals, all with corresponding 95% confidence intervals., Results: Non-Hispanic black patients (n = 421) have higher risk of overall mortality when compared to non-Hispanic white patients (n = 3255) with ependymoma (HR 1.48, CI 1.17-1.87). Risk of mortality was highest when comparing non-Hispanic black children under the age of 3 to non-Hispanic white children of the same age group (HR 3.05, CI 1.55-5.99). Mortality risk has increased among pediatric non-Hispanic black patients compared to pediatric non-Hispanic white patients between the years of 2006-2015, from previous rates between the years 1973-2005 (HR 1.95, CI 1.15-3.33 and HR 2.35, CI 1.24-4.44). Hispanic patients under 3 years had an increased risk of mortality compared to non-Hispanic white patients of this age group (HR 2.49, CI 1.37-4.53). Asian/Pacific Islander patients (n = 282) had no significant difference in outcomes when compared to non-Hispanic white patients., Conclusions: Our findings showed higher risk of mortality among non-Hispanic black patients compared to non-Hispanic white patients with ependymoma, with highest risk among pediatric patients. These results demonstrate significant need for research in survival outcomes for this disease.

Introduction: We report a retrospective cohort study aimed at presenting data on incidence, patient char-ac-teristics, tumour type, level of pathology, clinical status before and after surgery and complications in patients with surgically treated primary intraspinal tumours (PIST) in Western Denmark., Methods: Population-based data were retrieved from hospital files from 1 January 2010 to 31 December 2015., Results: In total, 78 males and 88 females with PIST were included in the study. Incidence per 100,000 persons per year in the population-based cohort was 2.18. The incidence of malignant PIST was 0.14 and the incidence of non-malignant PIST was 2.03. We found 25 extradural tumours, 100 intradural extramedullary tumours and 41 intramedullary tumours. Eleven were malignant and 155 were benign tumours. Schwannoma, meningioma and ependymoma were more common in adults, whereas haemangioblastoma, neurofibroma and epidermoid cysts were seen in 14 paediatric cases. Motor function disturbances were found in 38% of cases. Sensory disturbances were found in 54% of cases, and worsening of sensory functions was the most frequent post-operative sequela. Ataxia and neurogenic bowel/bladder dysfunction seem to constitute the highest risk in cases of intramedullary tumours. Pain was found in 75% of cases and was the most common symptom among all patients with PITS with a 58% improvement after surgery. Complications were recorded in 12% of cases., Conclusions: The incidence of PIST seems to be higher in Western Denmark than in other European studies. PIST are rare in children., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Although intracranial and spinal ependymomas are histopathologically similar, the molecular landscape is heterogeneous. An urgent need exists to identify differences in the genomic profiles to tailor treatment strategies. In the present study, we delineated differential gene expression patterns between intracranial and spinal ependymomas., Methods: We searched the Gene Expression Omnibus database using the term "ependymoma" and analyzed the raw gene expression profiles of 292 ependymomas (31 spinal and 261 intracranial). The gene expression data were analyzed to find differentially expressed genes (DEGs) between 2 regions. The fold change (FC) and false discovery rate (FDR) were used to assess DEGs after gene integration (|log 2 FC|>2; FDR P < 0.01). Enrichment and pathway analysis was also performed., Results: A total of 201 genes (105 upregulated and 96 downregulated) were significant DEGs in the data sets. The underexpression of NF2 in spinal ependymomas was statistically significant (FDR P = 7.91 × 10 -9 ). However, the FC of NF2 did not exceed the cutoff value (log 2 FC, -1.2). The top 5 ranked upregulated genes were ARX, HOXC6, HOXA9, HOXA5, and HOXA3, which indicated that spinal ependymomas frequently demonstrate overexpression of HOX family genes, which play fundamental roles in specifying anterior/posterior body patterning. Moreover, the gene ontology enrichment analysis specified "anterior/posterior pattern specification" and "neuron migration" in spinal and intracranial ependymomas, respectively., Conclusions: The most substantial magnitude of DEGs in ependymoma might be HOX genes. However, whether the differential expression of these genes is the cause or consequence of the disease remains to be elucidated in a larger prospective study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The goals of the study are to analyze postoperative outcomes and recurrence in cases of spinal cord and cauda equina ependymoma in each World Health Organization (WHO) Grade, and to examine the influence of extent of surgical removal on prognosis. Spinal ependymoma has a relatively high frequency among intramedullary spinal cord tumors. The tumor is classified in WHO guidelines as grades I, II, and III, but few studies have examined postoperative prognosis based on these grades., Methods: The records of 80 patients undergoing surgery for spinal cord and cauda equina ependymoma were examined in a multicenter study using a retrospective database. Neurological motor status, pathological type, extent of resection, and tumor recurrence were evaluated., Results: The histopathological types were grade I in 23 cases (myxopapillary: 21, subependymoma: 2), grade II in 52 cases, and grade III in 5 cases (including all anaplastic cases). Total resection was performed in 60 cases (83%), and eight cases had recurrence, including 2 in WHO grade I, 2 in grade II, and 4 in grade III. The 5-year recurrence-free survival rates were 90%, 91%, and 20% in grades I, II and III, respectively. Adjuvant radiotherapy for the local site was performed in 8 cases, including 3 in grade I and 5 in grade III; however, 4 of the 5 grade III cases (80%) had recurrence after radiotherapy. Among 59 patients with normal ambulation or independence without external assistance (McCormick Grade I or II), 53 (90%) maintained the same mobility after surgery. In cases that underwent total resection, the recurrence rate was significantly lower (p < 0.01). A good preoperative motor status also resulted in significantly better postoperative recovery of motor status (p < 0.05)., Conclusions: Total resection of spinal cord and cauda equina ependymoma leads to postoperative motor recovery and may reduce tumor recurrence. Therefore, early surgery for this tumor is recommended before aggravation of paralysis., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: Pediatric intramedullary spinal cord ependymomas represent a rare central nervous system neoplasm with few available data regarding incidence and outcomes. To this end, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of better understanding these tumors as well as improving outcomes. This retrospective study was undertaken to explore factors that may influence survival in pediatric patients with intramedullary spinal cord ependymomas., Methods: Using the SEER (Surveillance Epidemiology and End Results) database, a prospective cancer registry, we retrospectively assessed survival in histologically confirmed spinal ependymomas in patients 17 years of age and younger. Survival was described with Kaplan-Meier curves, and a multivariate regression analysis was used to assess the association of several variables with survival, controlling for confounding variables., Results: Invasive tumor extension (P < 0.001) was associated with decreased survival, whereas gross total resection (P = 0.028) correlated with better rates of survival. Age, gender, tumor size, tumor extension, the use and sequence of radiation therapy, or use of chemotherapy were not found to have a statistically significant association with survival outcomes., Conclusions: Invasive ependymomas occurring in the spine have a worse prognosis, whereas higher tumor grades do not clearly show worse rates of survival. Early diagnosis and surgery seem to be associated with improved survival and outcomes, whereas radiation therapy and chemotherapy have an unclear role., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We examined patterns of relapse and prognostic factors in children with intracranial ependymoma. Records of 82 children diagnosed with localized intracranial ependymoma were reviewed. 52% first presented to our institution after relapse. Median age at initial diagnosis was 4 years (range 0-18 years). Gender was 55% male. Initial tumor location was infratentorial in 71% and supratentorial in 29%. Histology was WHO Grade II in 32% and Grade III in 68%. As part of definitive management, 99% had surgery, 70% received RT (26% 2D/3D-conformal RT[CRT], 22% intensity-modulated RT [IMRT], 22% proton), and 37% received chemotherapy. Median follow-up was 4.6 years (range 0.2-32.9). Overall, 74% of patients relapsed (50% local, 17% distant, 7% local + distant) at a median 1.5 (range 0.1-17.5) years. Five-year OS and FFS for patients presenting prior to relapse are 70% (95% confidence interval [CI], 50-83%) and 48% (95% CI 30-64%), respectively. On log-rank, superior overall survival (OS) was demonstrated for gross total resection (p = 0.03). Superior failure-free survival (FFS) was demonstrated for age < 5 years (p = 0.04). No difference in OS or FFS was found between 2D/3D-CRT versus IMRT/proton (p > 0.05). On multivariate analysis, age ≤ 5 was independently associated with a lower risk of death and failure versus older patients (p < 0.05). Contrary to previous reports, young age may not be a poor prognostic factor in patients who can tolerate intensive treatment. Future studies examining patients stratified by clinical and molecular attributes are warranted.

OBJECTIVE Spinal ependymomas are rare glial neoplasms. Because their incidence is low, only a few larger studies have investigated this condition. There are no clear data concerning prognosis and therapy. The aim of the study was to describe the natural history, perioperative clinical course, and local tumor control of adult patients with spinal ependymomas who were surgically treated under modern treatment standards. METHODS The authors performed a multicenter retrospective study. They identified 158 adult patients with spinal ependymomas who had received surgical treatment between January 2006 and June 2013. The authors analyzed the clinical and histological aspects of these cases to identify the predictive factors for postoperative morbidity, tumor resectability, and recurrence. RESULTS Gross-total resection (GTR) was achieved in 80% of cases. At discharge, 37% of the patients showed a neurological decline. During follow-up the majority recovered, whereas 76% showed at least preoperative status. Permanent functional deterioration remained in 2% of the patients. Transient deficits were more frequent in patients with cervically located ependymomas (p = 0.004) and in older patients (p = 0.002). Permanent deficits were independently predicted only by older age (p = 0.026). Tumor progression was observed in 15 cases. The 5-year progression-free survival (PFS) rate was 80%, and GTR (p = 0.037), WHO grade II (p = 0.009), and low Ki-67 index (p = 0.005) were independent prognostic factors for PFS. Adjuvant radiation therapy was performed in 15 cases. No statistically relevant effects of radiation therapy were observed among patients with incompletely resected ependymomas (p = 0.079). CONCLUSIONS Due to its beneficial value for PFS, GTR is important in the treatment of spinal ependymoma. Gross-total resection is feasible in the majority of cases, with acceptable rates of permanent deficits. Also, Ki-67 appears to be an important prognostic factor and should be included in a grading scheme for spinal ependymomas.

Objective: In adults, spinal ependymomas constitute only 3% to 6% of central nervous system tumors. Because of their rarity and poor prognosis, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of improving outcome. The authors undertook this retrospective study to explore factors that may influence survival in adult patients with spinal ependymomas., Methods: Using the Surveillance, Epidemiology, and End Results database, a prospective cancer registry, the authors retrospectively assessed survival in histologically confirmed spinal ependymomas in patients 18 years of age and older. Survival was described with Kaplan-Meier curves, and a multivariate regression analysis was used to assess the association of several variables with survival while controlling for confounding variables., Results: Overall survival at 1 year, 3 years, and 5 years after diagnosis was 97.0%, 94.3%, and 93.3%, respectively. Patient age at diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.04-1.07, P < 0.001), tumor grade IV (HR 11.11, 95% CI 1.27-97.02, P = 0.032), and the use of radiation therapy during the course of treatment (HR 4.42, 95% CI 1.69-11.57, P = 0.003) were each associated with decreased survival. Gross total resection (HR 0.42, 95% CI 0.20-1.10, P = 0.026) was associated with improved overall survival. Gender, tumor size, and tumor extension were not found to impact survival., Conclusions: High-grade ependymomas occurring in the spine have a much worse prognosis than do those with lower grades. Early diagnosis and surgery appear to be associated with improved survival and outcomes, whereas radiation therapy has an unclear role., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades. The recent update of the World Health Organization classification of central nervous system tumors has already integrated one of these groups, and molecular classification will be part of future clinical trials to improve risk stratification. Clinical management of this rare disease is challenging, making professional experience and intensified multidisciplinary cooperation pivotal factors for treatment success. Novel research strategies are currently applied for target discovery in ependymomas since for most molecular groups, genetic drivers are unknown., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Surgical resection of intramedullary spinal cord ependymoma still remains the standard of care but is challenging and occasionally associated with poor outcome. The aim of this study is therefore to provide additional information regarding the natural history of conservatively treated symptomatic intramedullary spinal cord ependymoma. Retrospective, single center review of all patients with intramedullary spinal cord ependymoma treated conservatively (wait and see) between 1980 and 2016. The neurological outcomes at first presentation, as well as in long-term follow-up, were assessed using the modified McCormick Disability Scale and modified Rankin Scale. Thirteen of 41 patients were managed conservatively and were included in the study. Mean age at the admission was 49 years. There were seven women and six men. All patients were symptomatic at the time of presentation. The mean follow-up from admission to the last neurological examination was 47.9 months. The mean modified McCormick score in conservatively treated patients was 1.3 at admission and 1.6 (p = 0.3) at last follow-up. There was no significant neurological detoriation over time in conservatively managed patients as assessed by the modified Rankin Scale at first presentation and last follow-up (mRS scores of 0-2, 100 vs 92%; p = 0.9). This cohort of conservatively managed patients with symptomatic intramedullary spinal cord ependymoma was clinically stable throughout the follow-up period. Our data provide additional information for counseling patients with intramedullary spinal cord tumors who chose a nonoperative treatment.

Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Chicago's Ann & Robert H. Lurie Children's Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database. For the institutional cohort, we evaluated clinical and histopathological prognostic factors of overall survival (OS) and progression-free survival (PFS) using the log-rank test, and univariate and multivariate Cox proportional-hazards models. Overall survival rates were compared to those of the SEER cohort. Median follow-up time was 11 years. Ten-year OS and PFS were 50 ± 5% and 29 ± 5%, respectively. Findings were validated in the independent SEER cohort, with 10-year OS rates of 52 ± 3%. GTR and grade II pathology were associated with significantly improved OS. However, GTR was not curative for all children. Ten-year OS for patients treated with a GTR was 61 ± 7% and PFS was 36 ± 6%. Pathological examination confirmed most recurrent tumors to be ependymoma, and 74% occurred at the primary tumor site. Current treatment paradigms are not sufficient to provide long-term cure for children with ependymoma. Our findings highlight the urgent need to develop novel treatment approaches for this devastating disease.

Background: Fibroblast growth factor receptors (FGFRs) are well-known proto-oncogenes in several human malignancies and are currently therapeutically targeted in clinical trials. Among glioma subtypes, activating FGFR1 alterations have been observed in a subpopulation of pilocytic astrocytomas while FGFR3 fusions occur in IDH wild-type diffuse gliomas, resulting in high FGFR3 protein expression. The purpose of this study was to associate FGFR1 and FGFR3 protein levels with clinical features and genetic alterations in ependymoma and pilocytic astrocytoma., Methods: FGFR1 and FGFR3 expression levels were detected in ependymoma and pilocytic astrocytoma tissues using immunohistochemistry. Selected cases were further analyzed using targeted sequencing., Results: Expression of both FGFR1 and FGFR3 varied within all tumor types. In ependymomas, increased FGFR3 or FGFR1 expression was associated with high tumor grade, cerebral location, young patient age, and poor prognosis. Moderate-to-strong expression of FGFR1 and/or FGFR3 was observed in 76% of cerebral ependymomas. Cases with moderate-to-strong expression of both proteins had poor clinical prognosis. In pilocytic astrocytomas, moderate-to-strong FGFR3 expression was detected predominantly in non-pediatric patients. Targeted sequencing of 12 tumors found no protein-altering mutations or fusions in FGFR1 or FGFR3., Conclusions: Elevated FGFR3 and FGFR1 protein expression is common in aggressive ependymomas but likely not driven by genetic alterations. Further studies are warranted to evaluate whether ependymoma patients with high FGFR3 and/or FGFR1 expression could benefit from treatment with FGFR inhibitor based therapeutic approaches currently under evaluation in clinical trials.

Background: Primary brain tumors are common in childhood, but the etiology is largely unclear. As studies on birth weight as a risk factor for the occurrence of histologically specified tumors have been inconclusive, we decided to update a 2008 meta-analysis on the subject., Methods: A search strategy was performed in Medline and EMBASE for the period 2007-2016. We included six new studies and performed further subgroup analyses for medulloblastoma and primitive neuroectodermal tumors (PNETs). Dichotomous analyses were performed for low (2,500 g) and high birth weight (4,000 g cutoff point)., Results: Our results confirmed that high birth weight increases the risk of astrocytoma (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.23-2.09) and medulloblastoma/PNET. However, subgroup analysis revealed an increased risk of medulloblastoma (OR = 1.31, 95% CI: 1.08-1.58) but not of PNET (OR = 1.16, 95% CI: 0.92-1.46). Low birth weight was associated with an increased risk of medulloblastoma/PNET. Subgroup analysis for medulloblastoma and PNET revealed increased risk but CIs included zero. Neither low nor high birth weight was associated with the risk of ependymoma., Conclusions: While an association between high birth weight and astrocytoma was confirmed, more studies are needed to investigate medulloblastoma and PNET risk in children with high and low birth weight., (© 2016 Wiley Periodicals, Inc.)

Tumors of the posterior fossa represent the most common solid malignancy of childhood and can affect the visual system in several ways. This article outlines the relevant visual anatomy affected by these tumors and reviews the visual and oculomotor outcomes associated with the following 3 most common tumor types-medulloblastoma, juvenile pilocytic astrocytoma, and ependymoma. The available data suggest that the rate of permanent vision loss is low (5.9%-8.3%), with patients having juvenile pilocytic astrocytoma demonstrating the best outcomes. The rate of long-term strabismus (25%-29.1%) and nystagmus (12.5%-18%) is higher and associated with significant morbidity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

OBJECTIVE People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment. METHODS The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes. RESULTS Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11-53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3-57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas. CONCLUSIONS Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

Background: Outcomes projects can be a catalyst for determining disease- and treatment-related consequences for patients with rare tumors. The Adult Ependymoma Outcomes (AEO) survey uses self-reported experience to evaluate how this tumor affects patient groups throughout the illness trajectory., Methods: Patients completed the AEO survey via a Web-based portal. The survey included questions on treatment, tumor recurrence, and current health status; the MD Anderson Symptom Inventory Brain Tumor and Spine Tumor modules; and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)., Results: The sample included 264 participants (57% female) with a median age of 46 years (range, 18-77 years). Radiation treatment was commonly used for patients who had brain involvement (χ 2 (1) = 20.7; P < .001), underwent a partial resection (43%; χ 2 (3) = 15.4; P < .001), or had a grade 3 tumor (41%; χ 2 (2) = 18.8; P < .001). Recurrence occurred in a small group (29%), with grade 1 tumor patients 2.6 times more likely and grade 3 tumor patients 2.5 times more likely to experience recurrence than those with grade 2 tumors. Spine tumor patients had a higher symptom burden (mean, 2.8; scale, 0-10) than brain tumor patients (t(247) = -4.0), and they reported more moderate to severe symptoms (rating ≥ 5; 29%) than their counterparts (18%). Within the physical health portion of the SF-36, spine tumor patients reported worse health with respect to bodily pain (t(249) = 6.8; P < .001), physical functioning (t(252) = 4.1; P < .001), and vitality (t(202.2) = 3.0; P < .003)., Conclusions: These results demonstrate the feasibility of implementing outcomes projects that report on the clinical and demographic characteristics of a rare patient population, and they underscore the importance of outcomes data in understanding disease-related issues. Cancer 2017;123:494-501. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Purpose: Although ependymomas occur in both the brain and the spine, the prognosis is quite varied by tumor location. Spinal ependymomas usually follow a relatively benign course with more favorable prognosis than that of the intracranial ependymomas. The aim of this study is to evaluate the genetic differences between spinal ependymomas and their intracranial counterparts using a meta-analysis., Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library. Comparative or single arm genetic studies that enrolled patients with both intracranial and spinal ependymoma were included. The frequency of genetic aberration was calculated in each group. We calculated the odds ratio (OR) with 95 % confidence intervals (CIs) for direct comparative studies and the logit event rate (LER) and 95 % CI for single arm studies., Results: Twenty-five studies comprising of 380 spinal ependymomas and 964 intracranial ependymomas were compared to determine the association of the genetic differences of ependymomas at different locations. There were 25 comparable genetic aberrations between spinal and intracranial ependymomas. Among the genes, the NF2 mutation was significantly associated with the spinal ependymomas rather than with the intracranial ependymomas (spinal tumor: LER -0.750, 95 % CI -1.233 to -0.266, intracranial tumor: LER -3.080, 95 % CI -3.983 to -2.177). Intracranial ependymomas were found to be significantly associated with EPB41L3 deletion (OR 0.34; 95 % CI 0.14-0.80) and HIC1 methylation (OR 0.12; 95 % CI 0.02-0.68)., Conclusion: The genetic aberrations of spinal ependymomas are quite different from those of intracranial ependymomas. The difference in prognosis of ependymoma by location may be associated with genetic difference. A more detailed understanding of them may enable the development of targeted therapy and the estimation of prognosis.

Primary spinal myxopapillary ependymomas (MPE) in children are extremely rare. We examined the patient demographics, treatment modalities, and the associated outcomes of children with MPE using the Surveillance, Epidemiology, and End Results (SEER) national cancer database to gain a better understanding of these tumors. The SEER database (1973-2012) was used to analyze patients 21 years of age and younger with histologically confirmed MPE localized to the spinal cord or cauda equina. We analyzed patient demographics, extent of surgical resection, and radiation treatment. Overall survival was calculated using the Kaplan-Meier method. Statistical significance was defined as p < 0.05, with all data analyzed in IBM SPSS Statistics 21. 122 pediatric patients met inclusion criteria. The median age was 16 years (range 0-21) with 63 % male and 87 % Caucasian. The mean follow-up time was 4.5 years (95 % CI 3.93-5.07). Overall survival at 5 and 10 years was 97 and 95 %, respectively. We found 37 % underwent gross-total resection (GTR), 36 % subtotal resection (STR), and 27 % biopsy only. Patients who received GTR alone (n = 37) had a statistically significant increase in overall survival compared to those who received STR plus adjuvant radiation (n = 20) (Χ 2  = 5.9, p < 0.05). To our knowledge, this is the largest survival analysis of pediatric patients with MPE. Overall survival is excellent at the 5 and 10-year time points; however, GTR should be the goal of treatment when possible. For patients with MPE, future studies should focus on longer follow-up, the role of radiation, and the therapeutic approach at tumor recurrence.

Myxopapillary ependymoma (MPE) is an exceedingly rare tumor histology. While surgery is clearly the treatment of choice, controversy exists regarding the role of adjuvant radiotherapy (RT). Using the Surveillence, epidemiology, and end results (SEER) database, we aimed to determine the epidemiology, prognostic factors, and treatment-related outcomes for MPE. A total of 773 cases were found in the SEER database. The incidence in the American population was found to be 1.00 per million person-years. On multivariate analysis, receipt of surgery (HR = 0.14, CI = 0.06-0.35, p < 0.001), receipt of RT (HR = 4.06, CI = 1.87-8.81, p < 0.001), age less than 30 (HR = 0.24, CI = 0.08-0.72, p = 0.01), and Caucasian race (HR = 0.37, CI = 0.13-0.996, p = 0.049) were statistically significant prognostic factors. The mean tumor size among those receiving RT (4.6 cm) was significantly larger than among those not receiving RT (3.2 cm, p = 0.0002). Those who lived in metropolitan areas were more likely to receive RT than those who did not. Given multiple previous studies show that RT improves PFS and the discrepancy in tumor size, selection bias is likely a significant contributor to the apparent negative impact of RT on OS. Regardless, surgery remains the most crucial aspect in the care of patients with MPE.

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan-Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p<0.0001), high tumor grade (HR 1.82, p=0.005), and large tumor size (HR 1.66, p=0.008) were associated with poor survival. Females compared to males (HR 0.67, p=0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p=0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries.

Ependymomas are tumors that typically occur with an age-based site preference, with adults harboring supratentorial and spinal tumors and pediatric tumors being mainly in the posterior fossa. Despite their similar histologic appearance, the prognosis varies significantly by age and tumor location, with a better prognosis in increasing age. The mainstay of treatment remains surgical excision with or without radiation therapy as the tumor biology is poorly understood and chemotherapy is generally considered to be ineffective. More recently, molecular biology data have increased our understanding of the genetic and epigenetic changes that drive these tumors, but still it will take a lot of effort to find effective chemotherapeutic regimens. Currently, we are trying to define a subset of tumors, for which radiation therapy can be avoided., (© 2016 Elsevier B.V. All rights reserved.)

Background: Central nervous system (CNS) tumors are the most common cause of cancer-related death in children. Little is known about the demographics and treatment of pediatric brain tumors in low- and middle-income countries (LMICs)., Methods: We performed a retrospective chart review of all pediatric patients who presented to the neurosurgical service at Tribhuvan University Teaching Hospital in Kathmandu, Nepal from 2009-2014 and collected information on patients <18 years old who received a diagnosis of a CNS tumor. We analyzed age, gender, clinical presentation, extent of surgical resection, histopathology, and length of hospital stay. We also conducted a literature review using specific terminology to capture studies of pediatric neuro-oncologic epidemiology conducted in LMICs. Study location, length of study, sample size, study type, and occurrence of 4 common pediatric brain tumors were extracted., Results: We identified 39 cases of pediatric CNS tumors, with 62.5% observed in male children. We found that male children (median = 13 years) presented later than female children (median = 8 years). The most frequently observed pediatric brain tumor type was ependymoma (17.5%), followed by astrocytoma (15%) and medulloblastoma (15%). Surgical resection was performed for 80% of cases, and gross total resection reported in 62.9% of all surgeries. More than half (54.1%) of patients had symptoms for more than 28 days before seeking treatment. Symptomatic hydrocephalus was noted in 57.1% of children who presented with CNS tumors. The literature review yielded studies from 18 countries. Study length ranged from 2-20 years, and sample sizes varied from 35-1948. Overall, we found more pronounced variation in the relative frequencies of the most common pediatric brain tumors, compared with high-income countries., Conclusions: We present the first operative series of childhood CNS tumors in Nepal. Children often had delayed diagnosis and treatment of a tumor, despite symptoms. More comprehensive data are required to develop improved treatment and management algorithms in the context of a given country's demographics and medical capabilities for childhood CNS tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Due to increasing concerns regarding air pollution and childhood cancer, we conducted a population-based study evaluating the association between traffic-related hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter [DPM]) and the incidence of childhood central nervous system (CNS) tumors., Procedure: Information on children diagnosed with a CNS tumor at <15 years of age, in Texas, for the period of 2001-2009 (n = 1,949) was obtained from the Texas Cancer Registry. Information on the corresponding at-risk population was obtained from the United States (U.S.) Census. Annual census tract-level pollutant concentrations, estimated by the U.S. Environmental Protection Agency, were categorized based on quartiles (low, medium, medium-high, and high) of the statewide distribution. Multivariable Poisson regression was used to calculate adjusted incidence rate ratios (aIRR). Juvenile pilocytic astrocytomas (JPAs) (n = 384), other astrocytomas (n = 372), ependymomas (n = 142), medulloblastomas (n = 235), and primitive neuroectodermal tumors (PNET) (n = 47) were evaluated., Results: Census tracts with medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates (aIRR [95% confidence interval (CI)]: 1.46 [1.05-2.01] and 1.69 [1.22-2.33], respectively) compared with low concentrations. Census tracts with medium DPM concentrations had higher astrocytoma (aIRR [95%CI]: 1.42 [1.05-1.94]) and medulloblastoma (aIRR [95%CI]: 1.46 [1.01-2.12]) incidence rates compared with low concentrations. Increased concentrations of 1,3-butadiene and benzene were strongly associated with increased PNET incidence rates, but were not statistically significant. No associations were detected with JPA or ependymoma incidence., Conclusions: In one of the largest studies of its kind, our results suggest positive associations between hazardous air pollutants and incidence of astrocytoma (1,3-butadiene and DPM) and medulloblastoma (DPM)., (© 2015 Wiley Periodicals, Inc.)

This study reviews our tertiary hospital experience in an adult population of ependymoma patients. Ependymomas are uncommon tumours of the central nervous system (CNS) and the literature provides little information to guide management and predict prognosis. The prospectively maintained Australian Comprehensive Cancer Outcomes and Research Database of CNS tumours was searched for patients diagnosed with ependymomas at the Royal Melbourne Hospital between January 2008 and December 2013. A total of 39 adult patients with ependymoma were identified, including 13 with spinal myxopapillary ependymoma. The mean age at diagnosis was 44 years. All patients underwent surgical resection, 67% of whom had a gross macroscopic resection. Postoperative adjuvant radiotherapy was administered to 11 patients (30%), two (5%) died from progressive disease and seven (18%) developed recurrent disease. Our findings are consistent with the existing literature for patient demographics and the approach to treatment, whilst our clinical outcomes appear more favourable. This study provides the basis for further and necessary research, including determination of the molecular characterisation of these tumours and the identification of prognostic and predictive biomarkers and treatment targets., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Central nervous system tumors (CNST) are the most lethal of solid tumors in childhood cancer., Patients and Methods: We report incidence and survival data for all CNST (International Classification of Diseases for Oncology third edition, category III or Xa) recorded in children under 15 years of age by the Auvergne-Limousin cancer registry for the period 1986-2009., Results: Annual incidence of all CNST was 3.27 per 100,000 and the male to female ratio was 0.95. Over 45.0% of CNST were glial. Astrocytomas (36.2%) showed the highest incidence for each age group except between 1 and 4 years where embryonal tumors were more common. For all CNST, no significant variation in incidence over time was observed for the evaluated period of 23 years (annual percent change: -0.4%, 95% CI, [-2.8-2.1]). Globally, 5 years overall survival was 67% [59-73] and had increased by more than 16% between 1986-1999 and 2000-2009, mainly due to better survival for astrocytomas, other gliomas, ependymomas and choroid plexus tumors (P=0.01)., Conclusion: We report that the incidence of CNST in Auvergne-Limousin is similar to that in the literature and did not increase between 1986 and 2009. In addition, 5 years overall survival increased after 1999, especially for surgically treatable tumors., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution., Methods: Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival., Results: The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% (n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location (P < .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not by radiation (P < .01), as significantly increasing risk of early progression., Conclusions: We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unlabelled: Intramedullary spinal cord tumors (IMSCTs) are a rare pathology. They can be found at any age. Our experience with more than 507 surgeries for IMSCTs revealed some differences between pediatric and adult IMSCTs., Aim: We used a large surgical series to conduct comparative analysis of the main epidemiological characteristics of intramedullary tumors in children and adults and to identify possible differences., Material and Methods: Prospectively collected data from 224 pediatric and 242 adult patients operated by one surgeon (YK) for last 12 years were analyzed., Results: Pediatric IMSCTs are more extensive and children undergo treatment in worse clinical condition than adults. There are age-related differences in the tumor localization. The astrocytoma/ependymoma ratio was 83/17 in children and 21/79 in adults., Conclusion: We confirmed differences in IMSCTs in different age groups. Late diagnosis is a problem in the pediatric subgroup of IMSCT patients.

Ependymoma is a rare central nervous system tumor of adults. Reports of patient symptoms, interference patterns and costs encountered by patients and families are limited. Adult ependymoma patients completed the online Ependymoma Outcomes Questionnaire II. The survey assesses disease and functional status as well as socio-economic factors. Descriptive statistics were used to report disease characteristics as well as economic and social impact. Independent samples t test was used to test if differences exist between high- and low-income groups in terms of symptom severity. Correlations were calculated between symptoms and cost estimates. 86 international patients participated (male = 50 %). The economic analysis focused on 78 respondents from the US. 48 % were employed and 55 % earned ≥$60,000. Tumors were located in the brain (44 %), spine (44 %) or both (12 %). Spine patients compared to brain patients reported significantly worse pain (4.4 versus 2.2, p < .003), numbness (5.3 versus 2.2, p < .001), fatigue (5.1 versus 3.6, p < .03), changes in bowel patterns (3.8 versus 1.4, p < .003) and weakness (4.2 versus 2.1, p < .006). Brain patients compared with spine patients had increased lack of appetite (.4 versus 2, p < .014). Patients with lower income (≤$59,999) had more problems concentrating (p < .024) and worse cognitive module severity scores (p < .024). Estimated average monthly out-of-pocket spending was $168 for medical co-pays and $59 for prescription medication. Patients with ependymoma are highly affected by their symptoms. Spinal patients report higher severity of symptoms. Patients in the lower income group report significantly higher severity of cognitive symptoms independent of disease site.

Background: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR)., Methods: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada., Results: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022)., Conclusions: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

Study Design: Retrospective chart review., Objectives: Each type of intramedullary spinal cord tumor (IMSCT) has specific anatomical and pathological features visible on magnetic resonance (MR) imaging. The purpose of this study was to investigate the accuracy of preoperative IMSCT diagnosis using our diagnostic chart of tumor-specific MR imaging findings., Setting: Hamamatsu, Japan., Methods: From 2009 to 2013, 28 consecutive patients with IMSCT who underwent surgery in our university hospital were included in this study. There were 17 men and 11 women with an average age of 49 years (12-81). The pathological diagnoses were hemangioblastoma (12), ependymoma (11), astrocytoma (4) and squamous cell carcinoma (1). Tumor-specific MR imaging findings were as follows: ependymoma ((a) spinal cord swelling, (b) contrast effect with necrosis, (c) tumor in the center of the spinal cord), hemangioblastoma ((a) spinal cord swelling, (b) homogeneous contrast effect) and astrocytoma ((a) spinal cord swelling, (b) contrast effect is either, (c) eccentric tumor). Based on these features, we generated a diagnostic chart to investigate the MR imaging diagnosis accuracy for IMSCTs., Results: The accuracy of preoperative diagnosis was 89% (25/28 cases). Correct diagnoses were made in 100% of hemangioblastomas (12/12 cases), 90% of ependymomas (9/11 cases) and 100% of astrocytomas (4/4 cases)., Conclusions: Different types of IMSCTs exhibit unique MR imaging characteristics. These features can be used to preoperatively diagnose IMSCTs with high accuracy.

The determination of optimal therapy for ependymoma (EP) in infants is ongoing. We describe the incidence, management and outcomes of Canadian infants with EP to discern potential future research questions. Of 579 cases registered in a national database of children <36 months of age diagnosed with a brain tumor from 1990 to 2005, inclusive, 75 (13 %) were EP. These cases were analyzed. A mean annual age-adjusted incidence rate of 4.6 per 100,000 children years was calculated. The male:female ratio was 1.77. Of the tumors, 80 % were infratentorial in location, 67 % were WHO grade II histology, and 29 % were metastatic at diagnosis. All patients underwent a surgical procedure. A complete resection of the tumor was achieved in 56 % of the cases; 43 % of these patients survive while 36 % of the patients with tumors less than completely resected survive. Initial therapy consisted of surgery alone in 23 % of patients, or surgery plus chemotherapy (37 %), radiation therapy (RT; 19 %), or both (21 %). Any use of RT increased with patient age. The 5-year EFS rates for patients in each of the four treatment groups was 22, 11.5, 46.2 and 64.8 %, respectively. For all patients the median survival was 63 ± 6 months and 5-year overall survival was 55 ± 6 %. Patients treated with surgery and chemotherapy alone were younger and had a lower rate of survival than older patients who were more often treated with radiation therapy containing regimens. Further study is needed to determine which patients are optimally served with these treatment modalities.

Background: Tumours of the central nervous system are the second most common group of childhood cancers in 0-14 year olds (24% of total cancers) and represent a major diagnostic group in 15-24 year olds. The pilot case-control study aimed to establish methodologies for a future comprehensive aetiological investigation among children and young adults., Methods: Eligible cases were newly diagnosed with an intracranial tumour of neuroepithelial tissue aged 0-24 years. The pilot recruited patients through Leeds and Manchester Principal Treatment Centres. Controls were drawn from general practice lists. Controls were frequency matched by age and gender., Results: We interviewed 49 cases and 78 controls comprising 85% of the target sample size. Response rates were 52% for cases and 32% for controls. Completion of the questionnaire was successful, with a very small proportion of missing data being reported (5-10%). The age distribution of cases and controls was similar with around three-quarters of interviewed subjects aged 0-14. Half of cases and almost two-thirds of controls reported using a mobile phone with the majority starting between 10-14 years of age. Prevalence of breastfeeding was lower in cases than controls (Odds Ratio 0.4; 95% CI 0.2-1.2), whilst cases were more likely to be delivered by caesarean section (OR 1.6; 95% CI 0.6-4.4). Cases were significantly more likely to have a birthweight > 3.5 kg compared to controls. Cases were also more likely to come from a family with 3 or more siblings than controls (OR 3.0; 95% CI 0.7-13.6). The majority of participants (>80%) were in favour of taking either blood or saliva to aid molecular epidemiological research., Conclusions: Successful methods were established for identifying and recruiting a high proportion of case subjects, exploiting strong links with the clinical teams at the treatment centres. Control procedures proved more difficult to implement. However, working closely with national clinical and professional research networks will enable improved control identification and recruitment, with good prospects for collecting biological samples in the future.

Unlabelled: Intramedullary spinal cord tumors (IMSCTs) are a rare neurosurgical disease. There are a lot of controversies in their epidemiology. Most references were published in the 80-90ss. The authors describe and analyze the largest contemporary clinical series of IMSCTs treated by one surgeon (YK)., Material and Methods: 201 patients (aged 2 months - 18 years) with IMSCT operated on during the past 12 years., Results: A slight predominance of male patients was discovered. Astrocytomas account for 74% of all pediatric IMSCTs. Classic ependymomas are rare (5,5%). Pediatric spinal cord hemangioblastomas (HABs) are highly suspicious for von Hippel-Lindau disease., Conclusion: Benign histological variants of astrocytomas are the most common type of pediatric IMCTs. No gender or age differences in the incidence of most tumors (except for HABs) have been observed. Patients with intramedullary HAB should be routinely screened for von Hippel-Lindau disease. There are still a lot of uncertainties in the published data on epidemiology of IMSCTs.

Observation following gross-total resection (GTR) for non-anaplastic supratentorial ependymomas is often advocated based on small, retrospective series. The purpose of this study is to perform a population-based analysis to examine outcomes for this rare cohort of low-risk patients. A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute. We identified patients with supratentorial non-anaplastic ependymoma who underwent GTR alone or GTR followed by radiation. We identified 92 patients who met these criteria. The median age was 17.5 years (range 1-83) with the majority female (58 %) and white (75 %). Radiotherapy (RT) was delivered in half of patients. The 5-/10-year Kaplan-Meier estimated overall survival (OS) and cause-specific survival (CSS) for the overall cohort was 83.2/71.4 and 84.1/78.0 %, respectively. There was no evidence of decreased CSS (HR 0.52 [0.18-1.51]; p = 0.23) or OS (HR 0.63 [0.25-1.59]; p = 0.33) with the omission of RT on univariate analysis. Age ≥18 years correlated with worse OS (HR 4.01 [1.45-11.11]; p = 0.008) and CSS (HR 2.86 [0.99-8.31]; p = 0.05). RT did not impact outcome for this low-risk cohort of patients. Older age correlates with poor prognosis.

Patients with World Health Organization (WHO) grade II supratentorial ependymomas are commonly observed after gross total resection (GTR), although supporting data are limited. We sought to characterize the natural history of such tumors. We used the Surveillance, Epidemiology, and End Results program to identify 112 patients ages 0-77 diagnosed with WHO grade II ependymomas between 1988 and 2007, of whom 63 (56 %) and 49 (44 %) had supratentorial and infratentorial primaries, respectively. Inclusion criteria were strict to ensure patient homogeneity. Of 33 patients with supratentorial tumors after GTR, 18 (55 %) received adjuvant radiation therapy and 15 (45 %) did not. Ependymoma-specific mortality (ESM) was the primary endpoint. With a median follow up of 4.5 years, only 1 of 33 patients with supratentorial ependymoma died of their disease after GTR; the 5-year estimate of ESM in this population was 3.3 % (95 % CI 0.2-14.8 %). Among patients with infratentorial ependymomas after GTR, the 5-year estimate of ESM was 8.7 % (95 % CI 1.4-24.6 %). In patients with subtotally resected tumors, 5-year estimates of ESM in patients with supratentorial and infratentorial primaries were 20.1 % (95 % CI 8.0-36.2 %) and 12.3 % (95 % CI 2.9-28.8 %), respectively. Among the whole cohort, on both univariable and multivariable regression, extent of resection was predictive of ESM, while tumor location and use of radiation were not. After GTR, patients with WHO grade II supratentorial ependymomas have a very favorable natural history with low associated cancer-specific mortality. Observation, with radiation reserved as a salvage option, may be a reasonable postoperative strategy in this population.