Ependymoma is a tumor of the central nervous system that grows from the cells lining the fluid-filled spaces of the brain and spinal cord. It accounts for a small fraction of all brain tumors in adults but represents a much larger share in children, where it is one of the more common brain cancers. What makes ependymoma frustrating for patients, families, and researchers alike is that the name covers a surprisingly diverse set of diseases: tumors that look similar under the microscope can behave very differently depending on where they grow, what molecular changes drive them, and whether the patient is a child or an adult.
Where Ependymomas Come From
Ependymomas arise from ependymal cells, which line the ventricles of the brain and the central canal of the spinal cord. These cells help produce and circulate cerebrospinal fluid. Research over the past two decades has traced the origins of ependymoma more precisely to a type of neural progenitor called a radial glial cell. Studies have shown that ependymomas from different regions of the central nervous system express gene patterns that mirror the radial glia normally found in those same regions, and that cancer stem cells isolated from ependymomas display a radial glial identity and can form tumors when transplanted into mice.1PubMed. Radial glia cells are candidate stem cells of ependymoma This finding was an important step because it suggested that ependymomas arising in different parts of the nervous system are not just the same tumor in different spots; they are biologically distinct diseases generated by different populations of progenitor cells.2PubMed Central. Stem cells of ependymoma
Location Matters More Than You Might Think
Ependymomas are grouped by where they appear in the nervous system, and that location powerfully shapes symptoms, prognosis, and treatment strategy. The three broad regions are the supratentorial compartment (the cerebral hemispheres, above the cerebellum), the posterior fossa (the area around the cerebellum and brainstem), and the spinal cord.
In children, the majority of ependymomas arise in the posterior fossa, often wrapping around the brainstem in ways that make complete surgical removal difficult. These tumors tend to cause headaches, nausea, balance problems, and other signs of pressure buildup in the skull. In adults, spinal ependymomas are far more common, making up roughly two-thirds of cases in older age groups compared to under 10% in children.3PubMed Central. Comparison of epidemiology, treatments, and outcomes in pediatric versus adult ependymoma Spinal tumors typically cause back pain, limb weakness, or changes in bladder and bowel function as they press on the spinal cord or the bundle of nerves at the base of the spine.
A specific spinal subtype called myxopapillary ependymoma grows slowly near the base of the spine and is classified as a WHO Grade 2 tumor. It usually presents with signs of nerve compression in the lower body, such as radiating leg pain, weakness, or difficulty with bladder control.4PubMed Central. Spinal Myxopapillary Ependymoma Presenting With Isolated Intracranial Hypertension: A Case Report In rare instances, even a spinal tumor can cause headaches and vision changes by raising pressure inside the skull, which can initially mislead doctors looking for a brain problem.
Molecular Subgroups in the Brain
The 2021 update to the WHO classification of brain tumors pushed ependymoma firmly into the molecular era, recognizing that genetic and epigenetic markers can distinguish subgroups that behave very differently from one another even when they look identical under a microscope.5PubMed Central. Updates in the classification of ependymal neoplasms: The 2021 WHO Classification and beyond Two of the most clinically important divisions are in the supratentorial and posterior fossa regions.
Supratentorial Ependymoma
Supratentorial ependymomas are driven primarily by gene fusions. The most common involves a gene called ZFTA (previously known as C11orf95), which fuses with a partner gene called RELA, creating a protein that hijacks normal cell signaling and pushes cells toward uncontrolled growth.6Cancer Discovery. ZFTA-RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma A less common subtype is driven by fusions involving the YAP1 gene. These two fusion types activate different pathways, produce different clinical outcomes, and will likely require different treatments.7Developmental Neuroscience. The Intersection of Epigenetic Alterations and Developmental State in Pediatric Ependymomas The ZFTA-RELA subtype tends to be more aggressive, while YAP1 fusions are associated with a better prognosis.
Posterior Fossa Ependymoma
Posterior fossa ependymomas split into two main groups, called PFA and PFB. PFA tumors are the more dangerous of the two, occurring predominantly in very young children and carrying worse outcomes. They have limited treatment options compared to PFB tumors.8PubMed Central. Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas The distinction between PFA and PFB is largely epigenetic, meaning the difference lies not in which genes are present but in how those genes are switched on or off. Researchers have identified key genes whose expression levels differ sharply between the two groups, which may eventually point to new drug targets.9PubMed Central. Identification of key methylation differentially expressed genes in posterior fossa ependymoma based on epigenomic and transcriptome analysis
Spinal Ependymoma Genetics
The genetics of spinal ependymoma differ substantially from the brain-based forms. The most common recurring genetic event in spinal ependymoma involves the NF2 gene on chromosome 22. Loss of function in NF2, often through a combination of a gene mutation and loss of the corresponding chromosome region, is the hallmark finding. A large study using epigenetic profiling divided spinal ependymomas into two subtypes: subtype A, which typically carries NF2 mutations alongside loss of chromosome 22q, and subtype B, which does not. Subtype A tumors more often appeared in multiple locations along the spine and had significantly worse progression-free survival.10PubMed Central. Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation
A separate, rarer group of aggressive spinal ependymomas has been identified with high-level amplification of the MYCN gene. These tumors tend to be high-grade, lack NF2 changes, and have a unique molecular signature that sets them apart from the more common spinal forms.11PubMed Central. High level MYCN amplification and distinct methylation signature define an aggressive subtype of spinal cord ependymoma Recognizing this subtype matters because it responds poorly to standard treatment and may require different management strategies.
How Children and Adults Differ
Ependymoma in children and ependymoma in adults are, in many ways, different diseases wearing the same name. A large analysis comparing the two populations found that children had far higher rates of undifferentiated and anaplastic (aggressive) tumor types, while adults were much more likely to have the slower-growing myxopapillary variant. Only about 4% of children had myxopapillary tumors, compared to roughly 20-25% of adolescents and adults.12PubMed Central. Comparison of epidemiology, treatments, and outcomes in pediatric versus adult ependymoma
Treatment patterns also diverge. Children receive radiation therapy much more frequently, with about 62% of pediatric patients getting radiation compared to roughly 27% of older adults. This partly reflects the higher proportion of aggressive intracranial tumors in children and the use of radiation as a standard adjunct to surgery for those tumors. All-cause mortality was highest in the youngest and oldest groups, with adolescents faring best overall.13PubMed Central. Comparison of epidemiology, treatments, and outcomes in pediatric versus adult ependymoma
Surgery as the Foundation of Treatment
Complete surgical removal, known as gross total resection, is the single most important predictor of long-term survival across virtually all ependymoma subtypes. For spinal ependymomas, achieving gross total resection dramatically improves both progression-free and overall survival. One study of spinal cases reported that incomplete resection carried roughly seven times the risk of tumor progression compared to complete resection.14PubMed Central. Spinal ependymomas: benefits of extent of resection for different histological grades More recent work has confirmed this finding in independent patient series.15PubMed Central. Clinical presentation and extent of resection impacts progression-free survival in spinal ependymomas
For intracranial ependymomas in children, gross total resection is also strongly linked to improved survival, but it does not guarantee a cure. A multi-center study found that ten-year overall survival for children who had a complete resection was about 61%, and ten-year progression-free survival was only about 36%.16PubMed Central. Rethinking childhood ependymoma: a retrospective, multi-center analysis reveals poor long-term overall survival Those numbers underscore a difficult reality: even after what appears to be a successful surgery, many children will see their tumor return.
For the slow-growing myxopapillary variant in the lower spine, surgery alone is often curative. The vast majority of adult myxopapillary patients are treated with surgery, and only about 14% receive radiation, usually when complete removal is not possible or the tumor is large.17PubMed Central. National trends in management of adult myxopapillary ependymomas
Radiation Therapy and Its Trade-Offs
Radiation after surgery is standard for most intracranial ependymomas, particularly in children. Proton beam therapy has become increasingly popular for pediatric cases because it can deliver a precise dose to the tumor bed while reducing radiation exposure to surrounding healthy brain tissue. A study of 70 children treated with proton therapy reported three-year local control of 83%, progression-free survival of 76%, and overall survival of 95%.18PubMed Central. Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients A separate multi-center study confirmed that proton therapy provides disease control on par with traditional photon-based radiation without unexpected side effects.19PubMed. Proton Therapy for Pediatric Ependymoma: Mature Results From a Bicentric Study
Even with proton therapy’s advantages, radiation to a developing brain comes with real costs. Longitudinal data on children treated for ependymoma show that IQ and communication skills can decline over time after radiation, and children who develop severe hearing loss from treatment experience the steepest cognitive drops.20Neuro-Oncology. The impact of hearing loss on cognitive outcomes among children treated with radiation therapy for ependymoma One study that tracked children receiving localized radiation found that overall intelligence scores stayed relatively stable at two and five years after treatment, and mental processing speed was less affected than motor speed, but motor function was reduced in most children with tumors near the brainstem or cerebellum.21PubMed Central. Differential impact of tumor location, local and craniospinal irradiation on neuropsychological long-term outcome in children with medulloblastoma, ependymoma and supratentorial PNET The takeaway is that location of the tumor and the type and extent of radiation all influence which cognitive and physical abilities are most at risk.
Why Chemotherapy Has a Limited Role
Unlike many other childhood brain tumors, ependymoma responds poorly to chemotherapy. Reviews of clinical data have found that the response rate to single chemotherapy drugs is only about 11%, with fewer than 5% of patients achieving a complete response. Combinations of drugs perform somewhat better but still fall short of the results seen in other tumor types.22PubMed. Chemotherapy for intracranial ependymomas Protocols designed specifically for infants and very young children, where radiation is preferably delayed or avoided, have also not shown clear benefit from chemotherapy.23PubMed. Chemotherapy for intracranial ependymomas
One reason for this resistance may involve drug efflux pumps, proteins on the surface of ependymoma cells that actively expel chemotherapy drugs before they can do their work. Laboratory experiments have shown that blocking one such pump, called ABCB1, made ependymoma cells much more sensitive to common chemotherapy agents like vincristine and etoposide.24Scientific Reports. A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma Whether this approach can be translated into a workable clinical strategy remains to be seen, but it offers at least a partial explanation for why standard chemotherapy has been so disappointing.
Managing Recurrence
Recurrence is common in ependymoma, especially the aggressive pediatric subtypes. When the tumor comes back, the playbook is essentially the same: try again with surgery and radiation. A multi-institutional study of children with recurrent ependymoma found that achieving gross total resection before a second round of radiation significantly improved progression-free survival. For tumors in the posterior fossa specifically, complete resection before re-irradiation was linked to a meaningful improvement in overall survival as well.25PubMed Central. Reevaluating surgery and re-irradiation for locally recurrent pediatric ependymoma—a multi-institutional study The same study found that treating the entire brain and spine with radiation at recurrence reduced the rate of distant tumor spread compared to irradiating only the local tumor site.
Re-irradiation with proton therapy has also been studied. Data from one series showed six-year overall survival of about 56% and progression-free survival of about 26% after retreatment, with the most common pattern of failure being local recurrence again. Serious radiation-related side effects were relatively uncommon, with about 13% of patients experiencing moderate treatment-related changes.26International Journal of Radiation Oncology, Biology, Physics. Re-irradiation with Proton Therapy for Recurrent Ependymoma The fact that many patients survive multiple recurrences and retreatments distinguishes ependymoma from more rapidly fatal brain tumors, but the repeated surgeries and radiation courses take a cumulative toll.
Emerging Approaches and Research Frontiers
The molecular classification of ependymoma has opened the door to targeted therapies, though none have yet become standard of care. Researchers are exploring several drug classes, including agents that target growth-promoting enzymes, drugs that inhibit blood vessel formation around tumors, and compounds that interfere with telomerase, an enzyme that helps cancer cells maintain their ability to divide indefinitely. Immunotherapy approaches are also under investigation.27PubMed Central. The biology of ependymomas and emerging novel therapies The challenge is that each molecular subgroup may need its own targeted strategy, and the relative rarity of ependymoma makes clinical trials slower and harder to fill than for more common cancers.
One promising area is the development of better laboratory models. Patient-derived tumor organoids, miniature three-dimensional tissue cultures grown from a patient’s own tumor, have been established for pediatric brain tumors including ependymoma.28PubMed Central. Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments Organoids derived from ZFTA and YAP1 fusion-driven ependymomas retain the molecular signatures of the original tumors, allowing researchers to test drugs in a system that more faithfully reflects what happens in a patient’s body.29PubMed Central. Abstracts from the 2024 International Symposium on Pediatric Neuro-Oncology (ISPNO) This is a meaningful step because one reason drug development for ependymoma has been slow is the historical lack of good preclinical models. For decades, researchers struggled to grow ependymoma cells in the lab in ways that actually resembled the human disease.
Liquid biopsy, which aims to detect tumor DNA circulating in blood or cerebrospinal fluid, is another area of active investigation. A pilot study attempting to detect cell-free tumor DNA in the cerebrospinal fluid of patients with spinal ependymoma was unable to reliably find it, highlighting how early this technology is for this particular tumor type. The technique works better for some brain tumors than others, and ependymoma may present unique challenges because of its typically lower mutation burden and its location relative to cerebrospinal fluid flow.
Long-Term Quality of Life After Treatment
Surviving ependymoma is only part of the story. Because many patients are children at diagnosis, the long-term effects of treatment on a developing nervous system are a central concern. Posterior fossa tumors and their treatment particularly affect motor coordination, balance, and fine motor skills. Data from longitudinal studies suggest that tumor location in the back of the brain is a major risk factor for motor problems regardless of whether radiation is given, since the surgery itself can damage the cerebellum and brainstem.30PubMed Central. Differential impact of tumor location, local and craniospinal irradiation on neuropsychological long-term outcome in children with medulloblastoma, ependymoma and supratentorial PNET
Hearing loss is another concern, particularly when the tumor or the radiation field involves structures near the inner ear. Children who develop severe hearing loss after treatment show steeper declines in IQ and communication skills over time compared to those who retain their hearing.31Neuro-Oncology. The impact of hearing loss on cognitive outcomes among children treated with radiation therapy for ependymoma Early identification of hearing changes and intervention with hearing aids or other support may help protect cognitive development, though research on this is ongoing. Growth hormone deficiency, thyroid problems, and other endocrine issues can also arise after cranial radiation, making long-term follow-up with an endocrinologist a routine part of survivorship care for pediatric ependymoma patients.
For adults treated for spinal ependymoma, the survivorship picture is different. The main long-term concerns tend to be neurological deficits from the surgery itself, including numbness, weakness, or bladder problems, rather than the cognitive and developmental effects that dominate the pediatric conversation. The generally favorable prognosis of adult spinal ependymoma means that many patients live for decades after diagnosis, making the quality of those years just as important as the quantity.