{"entity":{"id":"ependymoma","kind":"cancer","name":"Ependymoma","aka":["Childhood ependymoma","Posterior fossa ependymoma","Supratentorial ZFTA fusion ependymoma","Myxopapillary ependymoma"],"tldr":"Ependymomas grow from the cells lining the fluid spaces of the brain and spinal cord, mostly in children under five. Removing the whole tumour followed by focused radiotherapy controls most cases; molecular groups defined in 2021 behave differently, with posterior fossa group A relapsing often, and there is no approved drug.","summary":"Ependymoma is a glial tumour arising along the ventricular system and spinal canal. The WHO 2021 classification replaced grade-based labels with molecular groups that carry prognostic weight: posterior fossa group A (PF-A, infants and young children, CpG hypermethylation with EZHIP overexpression and loss of H3K27me3, chromosome 1q gain marks high risk), posterior fossa group B (PF-B, older children and adults, favourable), supratentorial ZFTA (formerly RELA) fusion-positive (NF-kB driven), supratentorial YAP1 fusion-positive (young children, favourable), and spinal groups including myxopapillary ependymoma and MYCN-amplified spinal ependymoma. Few recurrent point mutations exist; the disease is largely driven by structural and epigenetic changes.\n\nTreatment is surgical: gross total resection is the strongest modifiable prognostic factor, and second-look surgery for residual disease is standard practice. Post-operative conformal radiotherapy to the tumour bed, including in children as young as one year, was established by the St Jude RT1 and COG ACNS0121 studies and controls disease without the whole-brain exposure of earlier eras; proton therapy is increasingly used to spare cochlea, hypothalamus and healthy brain. Chemotherapy has a limited role: it is used to bridge infants to radiotherapy or to enable second surgery, and the COG trial ACNS0831 tested maintenance chemotherapy after radiotherapy without establishing it as a universal standard. There is no approved targeted drug.\n\nThe active fronts are molecular risk stratification (SIOP Ependymoma II, ACNS0831 successors), reducing radiotherapy in favourable groups such as PF-B and ST-YAP1, and finding therapies for PF-A and ZFTA tumours, where relapse is common and repeated surgery and re-irradiation are the mainstay. Epigenetic dependencies (EZHIP and PRC2 biology in PF-A, NF-kB signalling in ZFTA), CDK4/6 inhibition and immunotherapy against fusion neoantigens are in preclinical and early clinical work.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Ependymoma","links":[{"label":"NCI PDQ: childhood ependymoma","url":"https://www.cancer.gov/types/brain/hp/child-ependymoma-treatment-pdq"},{"label":"Pajtler 2015: molecular classification of ependymal tumours (Cancer Cell)","url":"https://doi.org/10.1016/j.ccell.2015.04.002"},{"label":"ACNS0121: conformal radiotherapy in childhood ependymoma (JCO 2019)","url":"https://doi.org/10.1200/JCO.18.01765"}],"tags":["nci-coverage","paediatric","cns"],"related":["medulloblastoma","paediatric-low-grade-glioma","atrt","glioblastoma","spinal-cord-tumours"],"cancers":[],"sections":[],"technologies":["imrt-igrt","proton-therapy","methylation-profiling","mri","survivorship-care-plan"],"targets":["cdk4-6"],"drugs":["vincristine","carboplatin","cyclophosphamide","etoposide"],"companies":["childrens-oncology-group"],"institutions":["siop-europe","st-jude","dkfz"],"pathways":["epigenetic-reprogramming","inflammation-nfkb","hippo-yap"],"terms":["late-effects","ependymoma-molecular-groups"],"trials":["pediatric-match"],"people":[],"bottlenecks":["b-rare-cancers","b-survivorship"],"keyPapers":["paper-pajtler-cancer-cell"],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"Roughly one in ten childhood brain tumours, most under five years of age; also occurs in adults, mainly in the spine (NCI PDQ).","subtypes":["Posterior fossa group A (PF-A; EZHIP, H3K27me3 loss; 1q gain high risk)","Posterior fossa group B (PF-B; favourable)","Supratentorial, ZFTA fusion-positive","Supratentorial, YAP1 fusion-positive","Spinal ependymoma (including MYCN-amplified)","Myxopapillary ependymoma","Subependymoma"],"biomarkers":["Methylation-based molecular group","H3K27me3 loss and EZHIP expression (PF-A)","ZFTA or YAP1 fusion by FISH or sequencing","Chromosome 1q gain and 6q loss (PF-A risk)","MYCN amplification (spinal)","Extent of resection on post-operative MRI","Cerebrospinal-fluid cytology and spinal MRI for dissemination"],"standardOfCare":[{"setting":"Newly diagnosed intracranial ependymoma, age one year and over","approach":"Maximal safe resection, second-look surgery for residual disease, then conformal or proton radiotherapy to the tumour bed (ACNS0121 approach); craniospinal irradiation only for disseminated disease.","refs":["imrt-igrt","proton-therapy","mri","acns0121"],"guideline":{"version":"COG ACNS0121 (JCO 2019); NCI PDQ","url":"https://doi.org/10.1200/JCO.18.01765"}},{"setting":"Infants under one year or unresectable residual","approach":"Chemotherapy (vincristine, carboplatin, cyclophosphamide, etoposide-based) to delay radiotherapy or facilitate second surgery, per SIOP Ependymoma II and COG protocols.","refs":["vincristine","carboplatin","cyclophosphamide","etoposide"],"guideline":{"version":"SIOP Ependymoma II; NCI PDQ","url":"https://www.cancer.gov/types/brain/hp/child-ependymoma-treatment-pdq"}},{"setting":"Recurrent","approach":"Repeat resection and re-irradiation (focal or craniospinal) where feasible; no standard systemic therapy, so trial enrolment (including Pediatric MATCH-style molecular assignment) is recommended.","refs":["pediatric-match","proton-therapy"]}],"stateOfArt":["Molecular groups (PF-A, PF-B, ZFTA, YAP1, spinal) replaced grade as the basis of prognosis in WHO 2021 and are being used to de-escalate treatment for favourable groups.","Conformal and proton radiotherapy immediately after surgery, even in very young children, gives durable control with far less neurocognitive harm than older whole-brain approaches.","Gross total resection remains the single most important treatment step; second-look surgery is standard when residual disease is seen.","No drug has yet changed outcomes; epigenetic and fusion-directed strategies are the pipeline."],"history":[{"year":2009,"title":"Conformal radiotherapy safe and effective in young children","note":"St Jude RT1 (Merchant, Lancet Oncology) shows tumour-bed irradiation controls disease with preserved cognition.","refs":["imrt-igrt"]},{"year":2011,"title":"Two posterior fossa groups discovered","note":"Witt and colleagues (Cancer Cell) separate PF-A and PF-B by expression.","refs":[]},{"year":2014,"title":"C11orf95-RELA (ZFTA) fusion identified in supratentorial ependymoma","note":"Parker and colleagues (Nature) link the fusion to NF-kB activation.","refs":[]},{"year":2015,"title":"Nine molecular groups across the neuraxis","note":"Pajtler and colleagues (Cancer Cell) define the methylation-based classification later adopted by WHO.","refs":["methylation-profiling"]},{"year":2019,"title":"ACNS0121 confirms post-operative conformal radiotherapy","note":"COG phase 2 (JCO 2019) reports outcomes by extent of resection and molecular group.","refs":[]},{"year":2021,"title":"WHO 2021 adopts molecular groups for ependymoma","refs":[]}],"pipeline":["methylation-profiling","proton-therapy","pediatric-match"],"openProblems":["PF-A and ZFTA tumours relapse often and have no effective drug; EZHIP/PRC2 and NF-kB dependencies are being tested preclinically and in early trials.","Whether radiotherapy can be omitted or reduced in PF-B, YAP1 and completely resected favourable tumours; SIOP Ependymoma II and COG successors are stratifying by group.","Late effects of radiotherapy in very young children; proton therapy is expected to reduce them and is being tracked in registries.","Adult spinal and intracranial ependymoma lack dedicated trials and borrow from paediatric evidence."],"parent":"brain-tumours"},"route":"/cancers/ependymoma/","neighbours":{"cancer":[{"id":"atrt","kind":"cancer","name":"Atypical teratoid/rhabdoid tumour (ATRT)","route":"/cancers/atrt/"},{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"medulloblastoma","kind":"cancer","name":"Medulloblastoma","route":"/cancers/medulloblastoma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"papillary-tumour-pineal-region","kind":"cancer","name":"Papillary tumour of the pineal region","route":"/cancers/papillary-tumour-pineal-region/"},{"id":"spinal-cord-tumours","kind":"cancer","name":"Spinal cord tumours (intramedullary and intradural)","route":"/cancers/spinal-cord-tumours/"},{"id":"vestibular-schwannoma","kind":"cancer","name":"Vestibular schwannoma (acoustic neuroma)","route":"/cancers/vestibular-schwannoma/"}],"technology":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"institution":[{"id":"dkfz","kind":"institution","name":"German Cancer Research Center (DKFZ)","route":"/institutions/dkfz/"},{"id":"siop-europe","kind":"institution","name":"SIOP Europe (European Society for Paediatric Oncology)","route":"/institutions/siop-europe/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"hippo-yap","kind":"pathway","name":"Hippo-YAP/TAZ","route":"/pathways/hippo-yap/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"}],"term":[{"id":"ependymoma-molecular-groups","kind":"term","name":"Ependymoma molecular groups (PF-A, PF-B, ZFTA, YAP1, MYCN)","route":"/terms/ependymoma-molecular-groups/"},{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","route":"/terms/epigenetic-progenitor-theory/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"trial":[{"id":"nct06521567","kind":"trial","name":"A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer","route":"/trials/nct06521567/"},{"id":"acns0121","kind":"trial","name":"ACNS0121","route":"/trials/acns0121/"},{"id":"pediatric-match","kind":"trial","name":"NCI-COG Pediatric MATCH (APEC1621)","route":"/trials/pediatric-match/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}],"paper":[{"id":"paper-acns0121-ependymoma-conformal-radiotherapy-merchant-jco-2019","kind":"paper","name":"ACNS0121: conformal radiotherapy for paediatric ependymoma, chemotherapy for incompletely resected tumours and observation after complete resection","route":"/key-papers/paper-acns0121-ependymoma-conformal-radiotherapy-merchant-jco-2019/"},{"id":"paper-pajtler-cancer-cell","kind":"paper","name":"Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups","route":"/key-papers/paper-pajtler-cancer-cell/"}],"journal":[{"id":"brain-tumor-pathology","kind":"journal","name":"Brain tumor pathology","route":"/journals/brain-tumor-pathology/"},{"id":"cns-oncology","kind":"journal","name":"CNS oncology","route":"/journals/cns-oncology/"},{"id":"journal-of-neuro-oncology","kind":"journal","name":"Journal of neuro-oncology","route":"/journals/journal-of-neuro-oncology/"}]}}