CNS Tumors In Children Research Articles

Supratentorial Anaplastic Ependymoma with Bilateral Papilledema

Ependymomas constitute the third most common histological type of CNS tumor in children. Compared to classic cellular ependymoma (WHO grade II), anaplastic ependymoma is a more aggressive and less common subtype of ependymal neoplasm. We report a case of a supratentorial anaplastic ependymoma in a child presenting with a right sixth nerve palsy with bilateral papilledema. To our knowledge, the ophthalmic findings presented herein have not been previously reported in the context of this tumor type.

Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy.

Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT + chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95% CI: 4.6%-7.7%) at 20 years from diagnosis. Risks were highest for subsequent glioma, all grades (SIR = 57.2; 95% CI: 36.2-85.8) and acute myeloid leukemia (SIR = 31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT + chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated with multimodal therapy, cumulative incidence of SN was 12.0% (95% CI: 6.4%-19.5%) at 20 years, no different than survivors treated with RT alone (11.3%, P = .44). The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure to multimodal therapy compared with RT alone. Continued follow-up of survivors as they age is essential.

Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population.

Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982-2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P < .001). Within the survivor group, female gender and persistent visible physical sequelae predicted poorer outcomes in several of the studied domains. Tumor type and a history of cranial radiation therapy were associated with outcomes. An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention.

Abstract 5208: MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1

Abstract Medulloblastoma (WHO grade IV) is the most frequent malignant CNS tumor in children. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that target protein-coding mRNAs that play roles in a variety of cellular processes through regulating multiple target genes. In the present study, we analyzed miR-22 expression and its effect on cell proliferation and apoptosis in medulloblastomas. Quantitative RT-PCR revealed significantly lower expression of miR-22 in 19/25 (76%) medulloblastomas, D341, DAOY and ONS-76 medulloblastoma cells and primary cultured medulloblastomas cells, compared to normal cerebellum. Forced expression of miR-22 by lentiviral vector transfection reduced cell proliferation and induced apoptosis in DAOY and ONS-76 cells. DAOY cells with miR-22 overexpression in nude mice yielded tumors smaller than those originated from control DAOY cells. Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles; PAPST1 being the most significantly (10-fold) down-regulated gene. Quantitative RT-PCR revealed PAPST1 up-regulation in 18/25 (72%) medulloblastomas. Furthermore, the results of luciferase reporter assay in ONS-76 cells suggested that miR-22 directly targets the PAPST1 gene. Thus, frequently down-regulated miR-22 expression is associated with cell proliferation in medulloblastomas, at least in part via PAPST1, which is a novel target of miR-22. Citation Format: Qing-Fu Xu, Jesse Chung-sean Pang, Hui Yang, Sheng-Qing Lv, Hiroko Ohgaki. MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5208. doi:10.1158/1538-7445.AM2014-5208

Abstract 4307: MRI characterization of OKN-007 efficacy in a preclinical pediatric glioma model

Abstract High grade gliomas (HGG) are common primary CNS tumors in children. Here, we report the preliminary data about the efficacy of a nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tertbutyl nitrone (PBN)], in a preclinical pediatric HGG model (IC3752GBMV) by using Magnetic Resonance Imaging (MRI). The right cerebrum of eight week old male athymic nude mice was injected with IC3752GBMV pediatric HGG cells. The animals were divided in 2 groups: (A) untreated and (B) treated with OKN-007, which was given continuously (0.025% w/v) by drinking water after the tumors have reached volumes of 10-20 mm3. MRI was performed using a 7 Tesla Bruker BioSpin system and repeated weekly to access the tumor volumes. Diffusion-Weighted Imaging (DWI), Perfusion-Weighted Imaging (PWI), and Magnetic Resonance Spectroscopy (MRS) techniques were performed in both groups to evaluate the efficacy of OKN-007 in the pediatric cell lineage IC3752GBMV. The results of this study are preliminary and we are reporting here the data of only one animal of each group. For the OKN-007 treated group (88.58 mm3), the tumor volume was decreased when compared to the untreated group (139.3 mm3) at the last day point (day 51). Based on DWI, the ADC (Apparent Diffusion Coefficient) values (1x10-4 mm2/s) of the tumors normalized to contralateral brain were 0.949 for Group A, and 1.087 for Group B. The tumor of the OKN-007 treated animal had increased perfusion ratio (tumor/contralateral side of the brain) of 0.58 in comparison to the untreated control ratio of -5.28. The MRS data showed that the lipid (methylene)-to-creatine ratio was decreased in the pediatric glioma treated with OKN-007 versus the untreated tumor (14.89 and 23.75 respectively). This is the first report of evaluation of anti-cancer therapy efficacy of OKN-007 in a pediatric xenograft model by using DWI, PWI, and MRS techniques. Based on our preliminary results, DWI, PWI and MRS may provide some information useful in evaluating OKN-007 anti-cancer therapeutic response in pediatric HGG. OKN-007 decreased the tumor volume, and increased tumor perfusion rates, similar to what we found in a rat glioma model1. OKN-007 may also affect tumor metabolism in this pediatric HGG model, which was denoted by changes in the lipid (methylene)-to-creatine ratio. Similar results have been described previously in several different glioma models by our group2. In conclusion, the pediatric HGG IC3752GBMV model may facilitate biological studies and preclinical drug screenings for pediatric HGG. Furthermore, OKN-007 may be considered as a potential alternate and new therapy for pediatric HGG. This preliminary data will need to be repeated to confirm our findings. REFERENCES 1. Garteiser P. et al (2010). J Magn Reson Imaging. 31: 796-806. 2. Doblas S et al (2012). NMR Biomed.25:685-94. Note: This abstract was not presented at the meeting. Citation Format: Patricia Coutinho de Souza, Nataliya Smith, Charity Njoku, Debra Saunders, Krithika Balasubramanian, Rene Y. McNall, Xiao-Nan Li, Rheal A. Towner. MRI characterization of OKN-007 efficacy in a preclinical pediatric glioma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4307. doi:10.1158/1538-7445.AM2014-4307

Abstract 3089: (Epi)genetic profiling enables molecular re-classification of CNS-primitive neuroectodermal tumors

Abstract According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at a comprehensive molecular characterization of CNS-PNETs and compared our results to profiles of other brain tumor classes in order to define the biological nature of tumors diagnosed as CNS-PNETs. A collective of 197 fresh-frozen or paraffin-embedded tumor samples with an institutional diagnosis “CNS-PNET” was profiled for genome-wide DNA methylation patterns and copy-number alterations, complemented by transcriptomic profiling of a subset (n=63). (Epi-)genetic profiles of CNS-PNETs were compared to those of &amp;gt;1.000 other childhood brain tumors including embryonal, astrocytic, and ependymal entities, and their respective molecular subgroups. We screened selected groups of tumors for recurrent mutations and expression of established molecular markers. Five experienced neuropathologists independently revisited the histology of 48 CNS-PNETs. Bioinformatic analysis of DNA methylation and gene expression profiles using clustering methods and class prediction algorithms resulted in a clear segregation of pediatric brain tumors by histological entities and molecular subgroups. Exceptionally, profiles of tumors classified as “CNS-PNET” suggested significant overlap with various well-defined entities, including AT/RT, ETMR, high-grade glioma, medulloblastoma, and ependymoma. When screening CNS-PNETs with DNA methylation profiles highly resembling other entities, hallmark genetic alterations of these, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, or mutations/deletions of the SMARCB1 locus, were frequently detected. Molecularly distinct tumor subsets were associated with differential protein expression patterns of previously established subgroup markers INI-1, LIN28A, and OLIG2. Blinded histopathological evaluation resulted in a large proportion of CNS-PNETs being re-classified in line with affiliations suggested by molecular diagnostic tools. The correct classification of CNS-PNET remains challenging. Based on the detection of recurrent genetic aberrations, many cases can be reliably re-classified, indicating that a significant proportion of CNS-PNETs may comprise a variety of other tumor subtypes. These findings suggest that the use of established and novel subgroups markers is needed in order to assist the histopathological evaluation of these tumors. The molecular biology underlying distinct subsets of CNS-PNETs only remains to be elucidated. Citation Format: Dominik Sturm, Paul A. Northcott, David T.W. Jones, Andrey Korshunov, Daniel Picard, Peter Lichter, Annie Huang, Stefan M. Pfister, Marcel Kool. (Epi)genetic profiling enables molecular re-classification of CNS-primitive neuroectodermal tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3089. doi:10.1158/1538-7445.AM2014-3089

MOLECULAR (RE-)CLASSIFICATION OF CNS-PRIMITIVE NEUROECTODERMAL TUMORS

BACKGROUND: According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at a comprehensive molecular characterization of CNS-PNETs and compared our results to profiles of other brain tumor entities in order to define the biological nature of tumors diagnosed as CNS-PNETs. METHODS: A collection of 211 fresh-frozen or paraffin-embedded tumor samples with an institutional diagnosis “CNS-PNET” was profiled for genome-wide DNA methylation patterns and copy-number alterations, complemented by transcriptomic profiling of a subset (n = 71). (Epi-)genetic profiles of CNS-PNETs were compared to those of >3000 other childhood brain tumors including embryonal, astrocytic, and ependymal entities, and their respective molecular subgroups. We screened selected groups of tumors for recurrent mutations and expression of established molecular markers. RESULTS: DNA methylation and gene expression profiles showed a clear segregation of pediatric brain tumors by histological entities and molecular subgroups. Interestingly, CNS-PNET profiles showed a significant overlap with various well-defined entities, including AT/RT, ETMR, high-grade glioma, medulloblastoma, and ependymoma. When screening CNS-PNETs with profiles highly resembling other entities, hallmark genetic alterations of these, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, or mutations/deletions of the SMARCB1 locus, were frequently detected. Also, established protein markers, such as INI-1, LIN28A, and OLIG2, confirmed the reclassification of these CNS-PNETs. Strikingly, a subset (∼25%) of CNS-PNETs which could not be reclassified segregated into 3-4 distinct molecular subgroups, each with its own characteristic pattern of copy-number aberrations, DNA-methylation and gene expression. Currently, whole genome and RNA-sequencing of these distinct subgroups of CNS-PNETs is ongoing to reveal their underlying genetics. CONCLUSIONS: The correct classification of CNS-PNETs remains challenging. Based on the detection of recurrent genetic aberrations, many cases can be reliably re-classified, indicating that a significant proportion of CNS-PNETs may comprise a variety of other tumor subtypes. These findings suggest that the use of established and novel subgroups markers is needed in order to assist the histopathological evaluation of these tumors. In addition, we have identified a number of true CNS-PNET subtypes and are currently analyzing them in more detail in order to elucidate the genetics of these distinct groups. SECONDARY CATEGORY: Tumor Biology.

Surgical outcomes in spinal cord ependymomas and the importance of extent of resection in children and young adults

Ependymomas are a common type of CNS tumor in children, although only 13% originate from the spinal cord. Aside from location and extent of resection, the factors that affect outcome are not well understood. The authors performed a search of an institutional neuropathology database to identify all patients with spinal cord ependymomas treated over the past 20 years. Data on patient age, sex, clinical presentation, symptom duration, tumor location, extent of resection, use of radiation therapy, surgical complications, presence of tumor recurrence, duration of follow-up, and residual symptoms were collected. Pediatric patients were defined as those 21 years of age or younger at diagnosis. The extent of resection was defined by the findings of the postoperative MR images. A total of 24 pediatric patients with spinal cord ependymomas were identified with the following pathological subtypes: 14 classic (Grade II), 8 myxopapillary (Grade I), and 2 anaplastic (Grade III) ependymomas. Both anaplastic ependymomas originated in the intracranial compartment and spread to the spinal cord at recurrence. The mean follow-up duration for patients with classic and myxopapillary ependymomas was 63 and 45 months, respectively. Seven patients with classic ependymomas underwent gross-total resection (GTR), while 4 received subtotal resection (STR), 2 received STR as well as radiation therapy, and 1 received radiation therapy alone. All but 1 patient with myxopapillary ependymomas underwent GTR. Three recurrences were identified in the Grade II group at 45, 48, and 228 months. A single recurrence was identified in the Grade I group at 71 months. The mean progression-free survival (PFS) was 58 months in the Grade II group and 45 months in the Grade I group. Extent of resection is an important prognostic factor in all pediatric spinal cord ependymomas, particularly Grade II ependymomas. These data suggest that achieving GTR is more difficult in the upper spinal cord, making tumor location another important factor. Although classified as Grade I lesions, myxopapillary ependymomas had similar outcomes when compared with classic (Grade II) ependymomas, particularly with respect to PFS. Long-term complications or new neurological deficits were rare. Among patients with long-term follow-up, those who underwent GTR had a recurrence rate of 20% compared with 40% among those with STR or biopsy only, suggesting that extent of resection is perhaps a more important prognostic factor than histological grade in predicting PFS, which has been suggested by other data in the literature. Given the relative paucity of these lesions, collaborative multiinstitutional studies are needed, and such efforts should also focus on molecular and genetic analysis to refine the current classification system.

Epigenetic repression of the dopamine receptor D4 in pediatric tumors of the central nervous system

Epigenetic alterations are common events in cancer. Using a genome wide methylation screen (Restriction Landmark Genomic Scanning-RLGS) we identified the gene for the dopamine receptor D4 (DRD4) as tumor-specific methylated. As DRD4 is involved in early brain development and may thus be involved in developmentally dependent tumors of the CNS in children epigenetic deregulation of DRD4 and its functional consequences were analyzed in vitro. CpG methylation of DRD4 was detected in 18/24 medulloblastomas, 23/29 ependymomas, 6/6 high-grade gliomas, 7/10 CNS PNET and 8/8 cell lines by qCOBRA and bisulfite sequencing. Real-time RT-PCR demonstrated a significantly inferior expression of DRD4 in primary tumors compared to cell lines and non-malignant control tissues. Epigenetic deregulation of DRD4 was analyzed in reexpression experiments and restoration of DRD4 was observed in medulloblastoma (MB) cells treated with 5-Aza-CdR. Reexpression was not accompanied by demethylation of the DRD4 promoter but by a significant decrease of H3K27me3 and of bound enhancer of zeste homologue 2 (EZH2). Knockdown of EZH2 demonstrated DRD4 as a direct target for inhibition by EZH2. Stimulation of reexpressed DRD4 resulted in an activation of ERK1/2. Our analyses thus disclose that DRD4 is epigenetically repressed in CNS tumors of childhood. DRD4 is a direct target of EZH2 in MB cell lines. EZH2 appears to dominate over aberrant DNA methylation in the epigenetic inhibition of DRD4, which eventually leads to inhibition of a DRD4-mediated stimulation of the ERK1/2 kinase pathway.

Mortalidade por tumores do sistema nervoso central em crianças e adolescentes no Rio de Janeiro, Brasil, 1980-2009

OBJETIVO: Foi descrever o padrão da mortalidade por tumores do sistema nervoso central em crianças e adolescentes do município do Rio de Janeiro, Brasil, no período 1980-2009. MÉTODOS: Dados dos óbitos foram extraídos do Sistema de Informação sobre Mortalidade. Foram calculadas taxas brutas de mortalidade e específicas por sexo e faixa etária. Para a análise de tendência, utilizaram-se modelos de regressão polinomial e estimativa da variação percentual anual. RESULTADOS: Entre 1980 e 2009, os tumores do sistema nervoso central representaram 23% do total de óbitos por neoplasias no município do Rio de Janeiro em menores de 20 anos. Desses óbitos, 54,7% ocorreram no sexo masculino, 90,8% tinham localização encefálica e 87,7% eram malignos. No período, a mortalidade diminuiu 1,5% ao ano. A maior taxa foi 2,25/100000, em 1984, e a menor 0,68/100000, em 2008 CONCLUSÃO: Os tumores do sistema nervoso central em crianças e adolescentes representam hoje um problema de saúde pública, não obstante a queda da mortalidade observada no período estudado no município do Rio de Janeiro. Para avaliar se a diminuição da mortalidade é decorrente da redução na incidência ou da melhoria no tratamento desses tumores, seria importante realizar outros estudos que possam desvendar fatores associados ao seu desenvolvimento, diagnóstico e condutas terapêuticas.

Late Effects in Survivors of Childhood CNS Tumors: Review of Results From the Two Largest Survivorship Cooperative Groups

Late Effects in Survivors of Childhood CNS Tumors: Review of Results From the Two Largest Survivorship Cooperative Groups

Birth weight and other perinatal factors and childhood CNS tumors: A case–control study in California

AimsWe conducted a large registry-based study in California to investigate the association of perinatal factors and childhood CNS tumors, with analysis by tumor subtype. MethodsWe linked California cancer and birth registries to obtain information on 3308 cases and 3308 controls matched on age and sex. We examined the association of birth weight, gestational age, birth order, parental ages, maternal conditions during pregnancy, newborn abnormalities and the risk of childhood CNS tumors using conditional logistic regression, with adjustment for potential confounders. ResultsThe odds ratio (OR) per 1000g increase in birth weight was 1.11 (95% CI: 0.99–1.24) for total childhood CNS tumors, 1.17 (95% CI: 0.97–1.42) for astrocytoma and 1.28 (95% CI: 0.90–1.83) for medulloblastoma. Compared to average-for-gestational age, large-for-gestational age infants were at increased risk of glioma (OR=1.86, 95% CI: 0.99–3.48), while small-for-gestational age infants were at increased risk of ependimoma (OR=2.64, 95% CI: 1.10–6.30). Increased risk of childhood CNS tumors was observed for 5-year increase in maternal and paternal ages (OR=1.06, 95% CI: 1.00–1.12 and 1.05, 95% CI: 1.00–1.10 respectively). Increased risk of astrocytoma was detected for 5-year increase in paternal age (OR=1.08; 95% CI: 1.00–1.16) and increased risk of glioma for maternal age≥35 years old (OR=1.87; 95% CI: 1.00–3.52). Maternal genital herpes during pregnancy was associated with a pronounced increase in risk of total CNS tumors (OR=2.74; 95% CI: 1.16–6.51). Other (non-sexually transmitted) infections during pregnancy were associated with decreased risk of total CNS tumors (OR=0.28, 95% CI: 0.09–0.85). Maternal blood/immune disorders during pregnancy were linked to increased risk of CNS tumors (OR=2.28, 95% CI: 1.08–4.83) and medulloblastoma (OR=7.13, 95% CI: 0.82–61.03). Newborn CNS abnormalities were also associated with high risk of childhood CNS tumors (OR=4.08, 95% CI: 1.13–14.76). ConclusionsOur results suggest that maternal genital herpes, blood and immunological disorders during pregnancy and newborn CNS abnormalities were associated with increased risk of CNS tumors. Maternal infections during pregnancy were associated with decreased risk of CNS tumors. Advanced maternal and paternal ages may be associated with a slightly increased risk of CNS tumors. Factors associated with CNS tumor subtypes varied by subtype, an indicator of different etiology for different subtypes.

Disability, body image and sports/physical activity in adult survivors of childhood CNS tumors: population-based outcomes from a cohort study

Childhood CNS tumor survivors risk health and functional impairments that threaten normal psychological development and self-perception. This study investigated the extent to which health and functional ability predict adult survivors' body image (BI) and self-confidence regarding sports and physical activity. The study cohort covered 708 eligible ≥ 18 year old CNS tumor survivors, and data from 528 (75 %) were analyzed. Disability was estimated using the Health Utilities Index™ Mark2/3, a multidimensional self-report instrument. Physical self-confidence in terms of BI and sports/physical activity-related self-confidence (SPAS) were assessed using the BI and the Sports/Athletics modules of a standardized self-report assessment scale. In adjusted regression models, global health and functional status (GHFS) predicted BI (B = 0.94, 95 % CI 0.69-1.19) and SPAS (B = 0.79, 95 % CI 0.55-1.04). Emotion and pain, and to a lesser degree cognition, speech and vision disability, were associated with poorer BI and SPAS. Gender, sub-diagnosis, and time since diagnosis influenced the relationship between health status and physical self-confidence outcomes. Females had poorer GHFS, BI and SPAS than males. Decreased health and functional ability following childhood CNS cancer intrudes on physical self-confidence, with females being at heightened risk for both disability and negative self-confidence. Identified disability and gender-related risk calls for a follow-up plan that integrates treatment of psychological sequelae in lifetime monitoring of childhood CNS tumor survivors to restore and protect self-image and self-confidence, essential mental health correlates. An expanded plan should recognize the need for such services, optimizing life-long quality of survival for CNS tumor survivors.

Prognosis by tumor location for pediatric spinal cord ependymomas

Ependymoma is a common CNS tumor in children, with spinal cord ependymomas making up 13.1% of all ependymomas in this age group. The clinical features that affect prognosis in pediatric spinal cord ependymomas are not well understood. A comprehensive literature review was performed to determine whether a tumor location along the spinal cord is prognostically significant in children undergoing surgery for spinal cord ependymomas. A PubMed search was performed to identify all papers that contained data on patients with spinal cord ependymomas. Only pediatric patients (age < 18 years) who underwent resection with a clearly reported tumor location were included in the analysis. Myxopapillary tumors were excluded from study. Tumor location was subdivided into 6 regions: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus medullaris. Kaplan-Meier survival and Cox regression analyses were performed to determine the effects of tumor location on progression-free survival (PFS) and overall survival (OS). Fifty-eight patients who underwent resection of spinal cord ependymomas were identified. Ependymomas were located all along the spinal cord but occurred with the highest frequency in the cervical region (29.3%). Progression-free survival was significantly better in patients with tumors arising in the upper portion of the spinal cord (p = 0.031), which remained significant in the multivariate Cox regression analysis (p < 0.05). Moreover, OS was significantly better in patients with upper spinal cord ependymomas than in those harboring ependymomas in the lower spinal cord (p = 0.048). Although more common in adults, spinal ependymomas can occur anywhere along the spinal cord in the pediatric population; however, tumors occurring in the lower half of the spinal cord carry a worse prognosis with shorter PFS and OS. By comparison, ependymomas in the upper spinal cord recur later and less frequently, with little or no mortality in this patient group.

CNS tumours in children and adolescents - differences to adult patients

Brain tumours in children differ from brain tumours in adult patients with regard to epidemiology, localisation, clinical presentation, growth pattern, histology/molecular biology, therapy and follow-up care. CNS tumours are the most common type of solid tumour in children, accounting for 25% of all childhood neoplasms and surpassed only by leukemias. CNS tumours are the leading cause of cancer related deaths in children, accounting for 32% of all cancer deaths compared to 2% in adults. CNS tumours of childhood are very heterogeneous and therefore up to 90% of children with CNS tumours are treated according to international multicentre treatment protocols. The most frequent histology in children is low-grade glioma accounting for approximately 40% of all tumours, followed by the group of embryonal tumours including medulloblastoma, CNS primitive neuroectodermal tumour (CNS PNET), pineoblastoma and ATRT (18%). As 5- and 10-year survival rates of children with CNS tumours have increased, so has the concern over late effects of treatment. Due to the immaturity of the brain of children many long-term survivors have cognitive, endocrine, and neurologic deficits that lead to social handicaps and reduced quality of life.

Birth Anomalies and Risk of Childhood CNS Tumors

Researchers at Departments of Neurology, Pediatrics and Neurosurgery, Stanford University, CA linked 3733 patients aged 0 to 14 years with CNS tumors listed in the California Registry to a California birth certificate.

Meduloblastoma pediátrico, revisión y puesta al día

Medulloblastoma is the most common malignant CNS tumor in children. Although all medulloblastomas are classified as grade IV lesions, the wide histological and molecular variation among these tumors means that the risk and prognosis involved also vary widely. Imaging studies are important not only because the initial diagnostic evaluation indicates what type of surgery will be performed and has prognostic value, but also because it influences the postoperative treatment approach, providing, among other details, information about the dissemination of disease and remnants of the tumor after surgery, which are both risk factors in medulloblastomas. Improvements in our understanding of the biological and molecular characteristics of medulloblastoma promise a dramatic change in the accuracy of staging and treatment of this tumor in the near future that are sure to bring about further improvements in survival.

Review and update about medulloblastoma in children

Medulloblastoma is the most common malignant CNS tumor in children. Although all medulloblastomas are classified as grade IV lesions, the wide histological and molecular variation among these tumors means that the risk and prognosis involved also vary widely. Imaging studies are important not only because the initial diagnostic evaluation indicates what type of surgery will be performed and has prognostic value, but also because it influences the postoperative treatment approach, providing, among other details, information about the dissemination of disease and remnants of the tumor after surgery, which are both risk factors in medulloblastomas. Improvements in our understanding of the biological and molecular characteristics of medulloblastoma promise a dramatic change in the accuracy of staging and treatment of this tumor in the near future that are sure to bring about further improvements in survival.

Are early infectious exposures involved in the etiology of childhood CNS tumors?

Evaluation of: Schmidt LS, Kamper-Jorgensen M, Schmeigelow K et al. Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth. Br. J. Cancer 102(11), 1670–1675 (2010).Early infectious exposures have been implicated in the etiology of childhood CNS tumors. The article evaluated here assesses whether infectious exposure in the first years of life is involved by analyzing birth order, childcare attendance and seasonality of birth. The conclusion is that exposure to infectious disease in early childhood does not play an important role in the etiology of pediatric CNS tumors. It is noted that the measures used are only proxies for infectious exposures and, as such, may not accurately reflect the underlying infectious burden. Furthermore, this study is from the Nordic countries and from a later period than previous studies. Differences in patterns of exposure to infection may vary geographically between countries and may have changed over time. However, the authors have not excluded the possibility that a specific infectious agent is involved, and it is agreed here that future efforts should include a focus on a search for such an agent or agents, as well as formulating plausible, diagnostic-specific, mechanistic hypotheses.

Choroid plexus tumors in children less than 36 months: the Canadian Pediatric Brain Tumor Consortium (CPBTC) experience

Choroid plexus tumors (CPT) are rare pediatric tumors. A population-based study on choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP) was carried out to describe the incidence, demographic, and outcome data and to identify potential prognostic factors. The CPT population from the Canadian databank of CNS tumor in children ≤ 36 months diagnosed between 1990 and 2005 was reviewed Out of the 579 reported cases of CNS tumors, 37 were CPT. The annual age-adjusted incidence rate was 0.22 + 0.12 (95% CI 0.16-0.28)/100,000 children < 3 years. There were 21 (56.7%) CPP and 16 (43.3.5%) CPC. Twenty patients (54%) were males. Median age at diagnosis was 7 months(range 0-30). Ten patients(62.5%) with CPC and one with CPP were metastatic at diagnosis. Twenty patients with CPP (95%) had a complete resection, whereas 6/16 CPC (37.5%) achieved a resection >90%. Fourteen CPC patients received adjuvant chemotherapy. None of the 37 patients received adjuvant radiation. At completion of survey, all CPP and five CPC were alive. Median survival time for CPC patients was 15 months (0-120). One death was related to intraoperative hemorrhage, another to chemotherapy-induced toxicity, and one to secondary AML. Age at diagnosis, degree of resection and metastatic status were not significant prognostic factors for CPC. By contrast to CPC, CPP have an excellent prognosis following surgery alone. Survival of CPC remains poor. However, these data may suggest adjuvant chemotherapy can alter the aggressive natural history of CPC. As with other rare CNS tumors, international collaboration is required to identify optimal therapy.