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Recent Advances in the Classification and Treatment of Ependymomas

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
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Opinion Statement

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Ostrom QT, Gittleman H, de Blank PM, Finlay JL, Gurney JG, McKean-Cowdin R, et al. American Brain Tumor Association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro-Oncology. 2016;18(Suppl 1):i1–i50. doi:10.1093/neuonc/nov297.

    Article  PubMed  Google Scholar 

  2. •• Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27(5):728–43. doi:10.1016/j.ccell.2015.04.002. Basic science research utilizing DNA methylation profiles to group ependymal tumors by their similar epigenetic characteristics, identifying 9 molecular subgroups across age groups, locations and histopathology with more highly correlated survival outcomes than histopathologic grading alone

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-Oncology. 2016;18(7):902–13. doi:10.1093/neuonc/now016.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Healey EA, Barnes PD, Kupsky WJ, Scott RM, Sallan SE, Black PM, et al. The prognostic significance of postoperative residual tumor in ependymoma. Neurosurgery. 1991;28(5):666–71. discussion 71-2

    Article  CAS  PubMed  Google Scholar 

  5. Metellus P, Barrie M, Figarella-Branger D, Chinot O, Giorgi R, Gouvernet J, et al. Multicentric French study on adult intracranial ependymomas: prognostic factors analysis and therapeutic considerations from a cohort of 152 patients. Brain. 2007;130(Pt 5):1338–49. doi:10.1093/brain/awm046.

    Article  PubMed  Google Scholar 

  6. Paulino AC, Wen BC, Buatti JM, Hussey DH, Zhen WK, Mayr NA, et al. Intracranial ependymomas: an analysis of prognostic factors and patterns of failure. Am JClin Oncol. 2002;25(2):117–22.

    Article  Google Scholar 

  7. Vera-Bolanos E, Aldape K, Yuan Y, Wu J, Wani K, Necesito-Reyes MJ, et al. Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro-Oncology. 2015;17(3):440–7. doi:10.1093/neuonc/nou162.

    Article  PubMed  Google Scholar 

  8. Acquaye AA, Vera E, Gilbert MR, Armstrong TS. Clinical presentation and outcomes for adult ependymoma patients. Cancer. 2017;123(3):494–501. doi:10.1002/cncr.30355.

    Article  PubMed  Google Scholar 

  9. Walbert T, Mendoza TR, Vera-Bolanos E, Acquaye A, Gilbert MR, Armstrong TS. Symptoms and socio-economic impact of ependymoma on adult patients: results of the adult ependymoma outcomes project 2. J Neuro-Oncol. 2015;121(2):341–8. doi:10.1007/s11060-014-1638-4.

    Article  Google Scholar 

  10. Prayson RA. Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry. Ann Diagn Pathol. 1999;3(1):11–8.

    Article  CAS  PubMed  Google Scholar 

  11. Rushing EJ, Cooper PB, Quezado M, Begnami M, Crespo A, Smirniotopoulos JG, et al. Subependymoma revisited: clinicopathological evaluation of 83 cases. J Neuro-Oncol. 2007;85(3):297–305. doi:10.1007/s11060-007-9411-6.

    Article  Google Scholar 

  12. Prayson RA. Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunoreactivity. Mod Pathol. 1997;10(4):304–10.

    CAS  PubMed  Google Scholar 

  13. •• Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, et al. WHO classification of tumours of the central nervous system. Revised 4th Ed. World Health Organization Classification of Tumours. Lyon: International Agency for Research on Cancer (IARC); 2016. The 2016 update of the WHO classification of tumours of the central nervous system incorporates many of the new genetic findings that define ependymomas.

  14. •• Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, et al. C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature. 2014;506(7489):451–5. doi:10.1038/nature13109. Basic science research identifying oncogenic fusion genes in supratentorial ependymoma

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, et al. Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed. 2011;10:7. doi:10.1186/1477-5751-10-7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, et al. Prognostic factors in intracranial ependymomas in children. J Neurosurg. 2000;93(4):605–13. doi:10.3171/jns.2000.93.4.0605.

    Article  CAS  PubMed  Google Scholar 

  17. Ragel BT, Osborn AG, Whang K, Townsend JJ, Jensen RL, Couldwell WT. Subependymomas: an analysis of clinical and imaging features. Neurosurgery. 2006;58(5):881–890; discussion -90. doi:10.1227/01.neu.0000209928.04532.09.

    Article  PubMed  Google Scholar 

  18. Akamatsu Y, Utsunomiya A, Suzuki S, Endo T, Suzuki I, Nishimura S, et al. Subependymoma in the lateral ventricle manifesting as intraventricular hemorrhage. Neurologia Med Chir (Tokyo). 2010;50(11):1020–3.

    Article  Google Scholar 

  19. Carrasco R, Pascual JM, Navas M, Fraga J, Manzanares-Soler R, Sola RG. Spontaneous acute hemorrhage within a subependymoma of the lateral ventricle: successful emergent surgical removal through a frontal transcortical approach. Neurocirugia (Astur). 2010;21(6):478–83.

    Article  CAS  Google Scholar 

  20. Jallo GI, Zagzag D, Epstein F. Intramedullary subependymoma of the spinal cord. Neurosurgery. 1996;38(2):251–7.

    Article  CAS  PubMed  Google Scholar 

  21. Scheithauer BW. Symptomatic subependymoma. Report of 21 cases with review of the literature. J Neurosurg. 1978;49(5):689–96. doi:10.3171/jns.1978.49.5.0689.

    Article  CAS  PubMed  Google Scholar 

  22. Ralte AM, Rao S, Sharma MC, Suri A, Gaikwad S, Sarkar C. Myxopapillary ependymoma of the temporal lobe—report of a rare case of temporal lobe epilepsy. Clin Neuropathol. 2004;23(2):53–8.

    CAS  PubMed  Google Scholar 

  23. Tzerakis N, Georgakoulias N, Kontogeorgos G, Mitsos A, Jenkins A, Orphanidis G. Intraparenchymal myxopapillary ependymoma: case report. Neurosurgery. 2004;55(4):981.

    Article  PubMed  Google Scholar 

  24. Sato H, Ohmura K, Mizushima M, Ito J, Kuyama H. Myxopapillary ependymoma of the lateral ventricle. A study on the mechanism of its stromal myxoid change. Acta Pathol Jpn. 1983;33(5):1017–25.

    CAS  PubMed  Google Scholar 

  25. Chakraborti S, Govindan A, Alapatt JP, Radhakrishnan M, Santosh V. Primary myxopapillary ependymoma of the fourth ventricle with cartilaginous metaplasia: a case report and review of the literature. Brain Tumor Pathol. 2012;29(1):25–30. doi:10.1007/s10014-011-0059-8.

    Article  PubMed  Google Scholar 

  26. Lim SC, Jang SJ. Myxopapillary ependymoma of the fourth ventricle. Clin Neurol Neurosurg. 2006;108(2):211–4. doi:10.1016/j.clineuro.2004.12.010.

    Article  PubMed  Google Scholar 

  27. Sonneland PR, Scheithauer BW, Onofrio BM. Myxopapillary ependymoma. A clinicopathologic and immunocytochemical study of 77 cases. Cancer. 1985;56(4):883–93.

    Article  CAS  PubMed  Google Scholar 

  28. Burdick LM, Bergfeld W, Somani N, Piliang M. Subcutaneous myxopapillary ependymal rest: a potential sign of spinal dysraphism. J Am Acad Dermatol. 2011;65(4):851–4. doi:10.1016/j.jaad.2009.11.027.

    Article  PubMed  Google Scholar 

  29. Pica A, Miller R, Villa S, Kadish SP, Anacak Y, Abusaris H, et al. The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network. Int J Radiat Oncol Biol Phys. 2009;74(4):1114–20. doi:10.1016/j.ijrobp.2008.09.034.

    Article  PubMed  Google Scholar 

  30. Akyurek S, Chang EL, Yu TK, Little D, Allen PK, McCutcheon I, et al. Spinal myxopapillary ependymoma outcomes in patients treated with surgery and radiotherapy at M.D. Anderson Cancer Center. J Neuro-Oncol. 2006;80(2):177–83. doi:10.1007/s11060-006-9169-2.

    Article  Google Scholar 

  31. Chao ST, Kobayashi T, Benzel E, Reddy CA, Stevens GH, Prayson RA, et al. The role of adjuvant radiation therapy in the treatment of spinal myxopapillary ependymomas. J Neurosurg Spine. 2011;14(1):59–64. doi:10.3171/2010.9.spine09920.

    Article  PubMed  Google Scholar 

  32. Fegerl G, Marosi C. Stabilization of metastatic myxopapillary ependymoma with sorafenib. Rare Tumors. 2012;4(3):e42. doi:10.4081/rt.2012.e42.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Maeda S, Takahashi S, Koike K, Sato M. Primary ependymoma in the posterior mediastinum. Ann Thorac Cardiovasc Surg. 2011;17(5):494–7.

    Article  PubMed  Google Scholar 

  34. Zhou F, Song J, Mikolaenko I, Rosenblum M, Shukla PS. Pelvic ependymoma with clinical response to GnRH analog therapy: a case r eport with an overview of primary extraneural ependymomas. Int J Gynecol Pathol. 2015;34(5):450–8. doi:10.1097/pgp.0000000000000156.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sayegh ET, Aranda D, Kim JM, Oh T, Parsa AT, Oh MC. Prognosis by tumor location in adults with intracranial ependymomas. J Clin Neurosci. 2014;21(12):2096–101. doi:10.1016/j.jocn.2014.05.011.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Aizer AA, Ancukiewicz M, Nguyen PL, Macdonald SM, Yock TI, Tarbell NJ, et al. Natural history and role of radiation in patients with supratentorial and infratentorial WHO grade II ependymomas: results from a population-based study. J Neuro-Oncol. 2013;115(3):411–9. doi:10.1007/s11060-013-1237-9.

    Article  Google Scholar 

  37. Mansur DB, Perry A, Rajaram V, Michalski JM, Park TS, Leonard JR, et al. Postoperative radiation therapy for grade II and III intracranial ependymoma. Int J Radiat Oncol Biol Phys. 2005;61(2):387–91. doi:10.1016/j.ijrobp.2004.06.002.

    Article  PubMed  Google Scholar 

  38. Oh MC, Ivan ME, Sun MZ, Kaur G, Safaee M, Kim JM, et al. Adjuvant radiotherapy delays recurrence following subtotal resection of spinal cord ependymomas. Neuro-Oncology. 2013;15(2):208–15. doi:10.1093/neuonc/nos286.

    Article  CAS  PubMed  Google Scholar 

  39. Brandes AA, Cavallo G, Reni M, Tosoni A, Nicolardi L, Scopece L, et al. A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro-Oncologia. Cancer. 2005;104(1):143–8. doi:10.1002/cncr.21110.

    Article  PubMed  Google Scholar 

  40. Chamberlain MC, Johnston SK. Temozolomide for recurrent intracranial supratentorial platinum-refractory ependymoma. Cancer. 2009;115(20):4775–82. doi:10.1002/cncr.24524.

    Article  CAS  PubMed  Google Scholar 

  41. Fakhrai N, Neophytou P, Dieckmann K, Nemeth A, Prayer D, Hainfellner J, et al. Recurrent spinal ependymoma showing partial remission under Imatimib. Acta Neurochir. 2004;146(11):1255–8. doi:10.1007/s00701-004-0374-5.

    Article  CAS  PubMed  Google Scholar 

  42. Gornet MK, Buckner JC, Marks RS, Scheithauer BW, Erickson BJ. Chemotherapy for advanced CNS ependymoma. J Neuro-Oncol. 1999;45(1):61–7.

    Article  CAS  Google Scholar 

  43. Gramatzki D, Roth P, Felsberg J, Hofer S, Rushing EJ, Hentschel B, et al. Chemotherapy for intracranial ependymoma in adults. BMC Cancer. 2016;16:287. doi:10.1186/s12885-016-2323-0.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gilbert M, Yuan Y, Wani K, Wu J, Omuro A, Lieberman F, et al. AT-23A phase II study of lapatinib and dose-dense temozolomide (TMZ) for adults with recurrent ependymoma: a CERN clinical trial. Neuro-Oncology. 2014;16(suppl_5):v13. doi:10.1093/neuonc/nou237.23.

    Article  PubMed Central  Google Scholar 

  45. •• Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM, et al. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature. 2014;506(7489):445–50. doi:10.1038/nature13108. Basic science research identifying epigenomic alterations in pediatric posterior fossa ependymomas as both causative and plausible therapeutic targets

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Financial support came from the Department of Neurosurgery and the Hermelin Brain Tumor Center, Henry Ford Health System.

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Correspondence to Tobias Walbert MD.

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Heather Leeper has served as a consultant for Bristol-Myers Squibb.

Michelle M. Felicella declares that she has no conflict of interest.

Tobias Walbert has served on the advisory board of Novocure.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Neuro-oncology

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Leeper, H., Felicella, M.M. & Walbert, T. Recent Advances in the Classification and Treatment of Ependymomas. Curr. Treat. Options in Oncol. 18, 55 (2017). https://doi.org/10.1007/s11864-017-0496-7

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