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Journal of Neurosurgical Sciences Feb 2018Ependymomas are rare primary central nervous system tumors occurring in children and young adults. They can be indolent or locally aggressive depending on location,... (Review)
Review
Ependymomas are rare primary central nervous system tumors occurring in children and young adults. They can be indolent or locally aggressive depending on location, histology, and extent of resection. Treatment involves maximal surgical resection and usually focal radiation therapy, depending on the presence of residual disease and tumor grade. Chemotherapy has been studied for both adults and children but do not have an established role in adjuvant therapy. In both age groups, treatment with mainly cisplatin based regimens can be considered in the setting of residual disease after surgery or for salvage therapy when surgery or further radiation is not indicated. In children, chemotherapy can be considered in very young children to delay radiation or to increase the likelihood of complete resection in second look surgery. Targeted agents such as bevacizumab and lapatinib do not have a role in adjuvant therapy for ependymomas but are being explored for recurrent disease. This review discusses adjuvant therapy in both adult and child populations.
Topics: Adolescent; Antineoplastic Agents; Central Nervous System Neoplasms; Chemotherapy, Adjuvant; Child; Ependymoma; Female; Humans; Male; Young Adult
PubMed: 28945055
DOI: 10.23736/S0390-5616.17.04211-4 -
Pediatric Neurosurgery 2023Ependymoma is one of the most common malignant pediatric brain tumors and can be difficult to treat. Over the last decade, much progress has been made in the... (Review)
Review
BACKGROUND
Ependymoma is one of the most common malignant pediatric brain tumors and can be difficult to treat. Over the last decade, much progress has been made in the understanding of the underlying molecular drivers within this group of tumors, but clinical outcomes remain unchanged.
SUMMARY
Here, we review the most recent molecular advances in pediatric ependymoma, evaluate results of recent clinical trials and discuss the ongoing challenges in the field and questions that remain.
KEY MESSAGES
The field of ependymoma has vastly changed over the last several decades with ten distinct molecular subgroups now described, but much progress needs to be made in developing new therapeutic strategies and targets.
Topics: Child; Humans; Ependymoma; Brain Neoplasms
PubMed: 37231859
DOI: 10.1159/000530868 -
Nature Communications Nov 2022Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years...
Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years (5.8 ± 3.8) reveals stable molecular subtypes (RELA and PFA) and convergent DNA methylation reprogramming during serial relapses accompanied by increased orthotopic patient derived xenograft (PDX) (13/27) formation in the late recurrences. A set of differentially methylated CpGs (DMCs) and DNA methylation regions (DMRs) are found to persist in primary and relapse tumors (potential driver DMCs) and are acquired exclusively in the relapses (potential booster DMCs). Integrating with RNAseq reveals differentially expressed genes regulated by potential driver DMRs (CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and potential booster DMRs (PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). DMCs predicators of relapse are also identified in the primary tumors. This study provides a high-resolution epigenetic roadmap of serial EPN relapses and 13 orthotopic PDX models to facilitate biological and preclinical studies.
Topics: Humans; Child; Ependymoma; DNA Methylation; Recurrence; Epigenesis, Genetic; Symporters
PubMed: 36335125
DOI: 10.1038/s41467-022-34514-z -
Scientific Reports Mar 2022Adult spinal ependymoma presents a rare low-grade tumor entity. Due to its incidence peak in the fourth decade of life, it mostly affects patients during a...
Adult spinal ependymoma presents a rare low-grade tumor entity. Due to its incidence peak in the fourth decade of life, it mostly affects patients during a professionally and physically active time of life. We performed a retrospective monocentric study, including all patients operated upon for spinal ependymoma between 2009 and 2020. We prospectively collected data on professional reintegration, physical activities and quality-of-life parameters using EQ-5D and SF-36. Issues encountered were assessed using existing spinal-cord-specific questionnaires and free-text questions. In total, 65 of 114 patients agreed to participate. Most patients suffered from only mild pre- and postoperative impairment on the modified McCormick scale, but 67% confirmed difficulties performing physical activities in which they previously engaged due to pain, coordination problems and fear of injuries after a median follow-up of 5.4 years. We observed a shift from full- to part-time employment and patients unable to work, independently from tumor dignity, age and neurological function. Despite its benign nature and occurrence of formal only mild neurological deficits, patients described severe difficulties returning to their preoperative physical activity and profession. Clinical scores such as the McCormick grade and muscle strength may not reflect the entire self-perceived impairment appropriately.
Topics: Adult; Ependymoma; Humans; Neurosurgical Procedures; Quality of Life; Retrospective Studies; Return to Work; Spinal Cord Neoplasms; Treatment Outcome
PubMed: 35322104
DOI: 10.1038/s41598-022-09036-9 -
ZFTA-RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma.Cancer Discovery Sep 2021More than 60% of supratentorial ependymomas harbor a (ZR) gene fusion (formerly ). To study the biology of ZR, we developed an autochthonous mouse tumor model using...
More than 60% of supratentorial ependymomas harbor a (ZR) gene fusion (formerly ). To study the biology of ZR, we developed an autochthonous mouse tumor model using electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZR tumors by CUT&RUN, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin sequencing, and RNA sequencing and compared with human ZR-driven ependymoma. In addition to direct canonical NFκB pathway activation, ZR dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with PLAGL family transcription factor (TF) motifs. ZR activates gene expression programs through recruitment of transcriptional coactivators (Brd4, Ep300, Cbp, Pol2) that are amenable to pharmacologic inhibition. Downstream ZR target genes converge on developmental programs marked by PLAGL TF proteins, and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks. SIGNIFICANCE: Ependymomas are aggressive brain tumors. Although drivers of supratentorial ependymoma (- and -associated gene fusions) have been discovered, their functions remain unclear. Our study investigates the biology of -driven ependymoma, specifically mechanisms of transcriptional deregulation and direct downstream gene networks that may be leveraged for potential therapeutic testing..
Topics: Animals; DNA-Binding Proteins; Disease Models, Animal; Ependymoma; Mice; Supratentorial Neoplasms; Transcription Factor RelA; Transcription Factors
PubMed: 33741710
DOI: 10.1158/2159-8290.CD-20-1066 -
Neuro-oncology Jun 2021
Topics: Adolescent; Brain Neoplasms; Child; Ependymoma; Humans
PubMed: 33728470
DOI: 10.1093/neuonc/noab066 -
Brain Pathology (Zurich, Switzerland) Sep 2020Advances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO)... (Review)
Review
Advances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO) classification of CNS tumors (2016) have prompted the cIMPACT-NOW group to recommend a new classification. Separation of ependymal tumors by anatomic site is an important principle of the new classification and was prompted by methylome profiling data to indicate that molecular groups of ependymal tumors in the posterior fossa and supratentorial and spinal compartments are distinct. Common recurrent genetic or epigenetic alterations found in tumors belonging to the main molecular groups have been used to define tumor types at intracranial sites; C11orf95 and YAP1 fusion genes for supratentorial tumors and two types of posterior fossa ependymoma defined by methylation group, PFA and PFB. A recently described type of aggressive spinal ependymoma with MYCN amplification has also been included. Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT-NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status.
Topics: Brain Neoplasms; Central Nervous System Neoplasms; Ependyma; Ependymoma; Glioma; Humans; Supratentorial Neoplasms
PubMed: 32502305
DOI: 10.1111/bpa.12866 -
Neuro-oncology Jun 2022SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3-21 years... (Clinical Trial)
Clinical Trial
BACKGROUND
SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3-21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide, and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.
METHODS
Seventy-four participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3, and pAKT status were evaluated.
RESULTS
Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (P = .003, HR = 2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (P = .005, HR = 2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (P = .003, HR = 2.70, 95%CI 1.49-6.10 and P = .014, HR = 5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (P = .003, HR = 4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%.
CONCLUSIONS
Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss, and hTERT expression were all associated with poorer survival outcomes.
Topics: Child; Chromosome Aberrations; Cyclophosphamide; Ependymoma; Etoposide; Follow-Up Studies; Histones; Humans; Treatment Outcome; Vincristine
PubMed: 35018471
DOI: 10.1093/neuonc/noac012 -
Journal of Veterinary Diagnostic... Sep 2022Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes...
Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes and pseudorosettes. Oligodendrocyte transcription factor (OLIG2) is expressed in oligodendrocyte precursor cells and mature oligodendrocytes. Although widely used as a diagnostic marker for most gliomas, OLIG2 is reported to have minimal immunolabeling in ependymomas. Here we characterize the OLIG2 immunolabeling pattern in 19 cases of feline ependymoma, which occurred predominantly in the lateral and third ventricles. Immunohistochemistry for GFAP was variable in 14 cases and was typically localized in the cytoplasmic processes of the neoplastic ependymal cells, especially in the rosettes and pseudorosettes. Nuclear OLIG2 immunolabeling was present in 17 cases and varied in intensity from weak (4 cases) to strong (13 cases). The distribution of OLIG2 immunolabeling within the neoplasms included none (2 cases), <25% (7 cases), 25-50% (6 cases), 51-75% (2 cases), and >75% (3 cases). OLIG2 immunolabeling intensity and distribution is widespread in feline ependymoma, in contrast to ependymomas in other species, and should not be relied upon as a specific marker for feline oligodendroglioma.
Topics: Animals; Brain Neoplasms; Cat Diseases; Cats; Ependymoma; Glioma; Immunohistochemistry; Oligodendroglioma
PubMed: 35762120
DOI: 10.1177/10406387221107898 -
Medical Science Monitor : International... Oct 2018BACKGROUND The aim of this study was to assess the clinical and radiological outcomes of surgical treatment for primary spinal ependymoma in children. MATERIAL AND...
BACKGROUND The aim of this study was to assess the clinical and radiological outcomes of surgical treatment for primary spinal ependymoma in children. MATERIAL AND METHODS Medical records of 46 primary spinal ependymoma patients who underwent surgery in BRSHH hospital during a 12-year period from 2004 to 2015 were retrospectively reviewed. All pediatric patients (patient age <18 years) were selected as the core sample used for this study. RESULTS This series included 1 female and 2 male patients between the ages of 9 and 17 years with mean age 13.3±3.9 years. The mean preoperative course was 9.1±10.5 months. The most common location was the lumbar spinal cord (n=2). The most common presenting symptoms was lower-limb weakness and numbness. Two tumors were located intradural-intramedullary and 1 was located intradural-extramedullary. Gross-total resection (GTR) was achieved in 2 patients, and a near-total resection was performed in 1 patient. No adjuvant treatment was received. The mean follow-up duration was 51.3±37.6 (17-98) months. No complications were recorded. Functional assessment of all patients by the latest follow-up evaluation showed good progress even though the patient is not fully recovered. At 6.3 years after the first operation, 1 patient presented with drop-seeding metastasis. No patients had neurofibromatosis type 2. CONCLUSIONS Laminoplasty and intraoperative neurophysiological monitorization are essential in surgical treatment of pediatric spinal ependymomas. GTR and recovery in pediatric spinal ependymoma are more likely than in adults. Despite the GTR, the risk of drop metastasis remains. Therefore, close clinical and radiological follow-up is recommended.
Topics: Adolescent; Adult; Child; Disease-Free Survival; Ependymoma; Female; Follow-Up Studies; Glioma; Humans; Kaplan-Meier Estimate; Male; Neoplasm Recurrence, Local; Neurosurgical Procedures; Retrospective Studies; Spinal Cord Neoplasms; Spine; Treatment Outcome
PubMed: 30287802
DOI: 10.12659/MSM.910447