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Ependymoma

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Brain Tumors in Children

Abstract

Ependymoma is one of the most common pediatric brain tumors and constitutes about 10% of all malignant neoplasms in the pediatric brain. Affected children and infants have a very poor prognosis. The majority of cases arise within the posterior fossa (70%), followed by the supratentorial region (25%) and the spinal cord (5%). Several independent studies have identified compartment-specific molecular subtypes of ependymomas. Within the posterior fossa, two molecular subtypes have been defined: Group A Ependymoma (PF-EPN-A) found in young children and infants, and Group B (PF-EPN-B) tumors diagnosed in adolescents and adults. Two additional predominantly pediatric ependymoma subtypes occur in the supratentorial region. One subgroup, ST-EPN-RELA, is characterized by fusions of the RELA gene, while the other subgroup, ST-EPN-YAP1, is defined by fusions to the oncogene YAP1. These molecular subgroups outperform the current histopathological classification in terms of clinical utility. The vast majority of high-risk ependymoma patients, for whom effective therapeutic concepts are desperately needed, are children with tumors belonging to the molecular subgroups PF-EPN-A and ST-EPN-RELA. This points to the striking relevance of molecular classification for the future clinical management of ependymoma. The mainstays of treatment are maximal safe surgery and radiotherapy, while results from chemotherapeutic approaches have been mostly disappointing. A paucity of identified actionable targets combined with only limited availability of in vitro and in vivo model systems has significantly hampered efforts to better understand tumor biology and to test novel targeted therapies for ependymoma. Several compounds that had been predicted based on preclinical analyses to potentially be effective against primary ependymoma are under clinical evaluation but have not yet demonstrated convincing results. The implementation of a new molecular classification scheme for more precise risk stratification within clinical trials, the identification of novel biology driven therapeutic concepts, as well as the development of adequate preclinical models represent the current paramount challenges for ependymoma research and treatment.

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Authors and Affiliations

  1. Hopp-Children’s Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany

    Hendrik Witt & Kristian W. Pajtler

  2. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Hendrik Witt & Kristian W. Pajtler

  3. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany

    Hendrik Witt & Kristian W. Pajtler

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  1. Hendrik Witt
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Correspondence to Hendrik Witt .

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Editors and Affiliations

  1. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Amar Gajjar

  2. Children’s National Medical Center, George Washington University, Silver Spring, WA, USA

    Gregory H. Reaman

  3. Cincinnati, OH, USA

    Judy M. Racadio

  4. Medpace, Cincinnati, OH, USA

    Franklin O. Smith

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Witt, H., Pajtler, K.W. (2018). Ependymoma. In: Gajjar, A., Reaman, G., Racadio, J., Smith, F. (eds) Brain Tumors in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-43205-2_8

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