Ependymoma

 

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Abstract

Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades. The recent update of the World Health Organization classification of central nervous system tumors has already integrated one of these groups, and molecular classification will be part of future clinical trials to improve risk stratification. Clinical management of this rare disease is challenging, making professional experience and intensified multidisciplinary cooperation pivotal factors for treatment success. Novel research strategies are currently applied for target discovery in ependymomas since for most molecular groups, genetic drivers are unknown.

• References

• 1 Villano JL, Parker CK, Dolecek TA. Descriptive epidemiology of ependymal tumours in the United States. Br J Cancer 2013; 108 (11) 2367-2371
  CrossrefPubMedGoogle Scholar
• 2 Vera-Bolanos E, Aldape K, Yuan Y. , et al; CERN Foundation. Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro-oncol 2015; 17 (03) 440-447
  PubMedGoogle Scholar
• 3 Kilday JP, Rahman R, Dyer S. , et al. Pediatric ependymoma: biological perspectives. Mol Cancer Res 2009; 7 (06) 765-786
  CrossrefPubMedGoogle Scholar
• 4 Purdy E, Johnston DL, Bartels U. , et al. Ependymoma in children under the age of 3 years: a report from the Canadian Pediatric Brain Tumour Consortium. J Neurooncol 2014; 117 (02) 359-364
  CrossrefPubMedGoogle Scholar
• 5 Yao Y, Mack SC, Taylor MD. Molecular genetics of ependymoma. Chin J Cancer 2011; 30 (10) 669-681
  CrossrefPubMedGoogle Scholar
• 6 Jain A, Amin AG, Jain P. , et al. Subependymoma: clinical features and surgical outcomes. Neurol Res 2012; 34 (07) 677-684
  CrossrefPubMedGoogle Scholar
• 7 Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncol 2016; 18 (07) 902-913
  PubMedGoogle Scholar
• 8 Cimino PJ, Agarwal A, Dehner LP. Myxopapillary ependymoma in children: a study of 11 cases and a comparison with the adult experience. Pediatr Blood Cancer 2014; 61 (11) 1969-1971
  CrossrefPubMedGoogle Scholar
• 9 Fassett DR, Pingree J, Kestle JR. The high incidence of tumor dissemination in myxopapillary ependymoma in pediatric patients. Report of five cases and review of the literature. J Neurosurg 2005; 102 (1, Suppl): 59-64
  CrossrefPubMedGoogle Scholar
• 10 Louis DN, Ohgaki H, Wiestler OD. , et al. WHO Classification of Tumours of the Central Nervous System. Revised 4th ed. Lyon, France: International Agency for Research on Cancer; 2016
  Google Scholar
• 11 Ellison DW, Kocak M, Figarella-Branger D. , et al. Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 2011; 10: 7
  CrossrefPubMedGoogle Scholar
• 12 Parker M, Mohankumar KM, Punchihewa C. , et al. C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 2014; 506 (7489): 451-455
  CrossrefPubMedGoogle Scholar
• 13 Godfraind C. Classification and controversies in pathology of ependymomas. Childs Nerv Syst 2009; 25 (10) 1185-1193
  CrossrefPubMedGoogle Scholar
• 14 Hovestadt V, Jones DT, Picelli S. , et al. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 2014; 510 (7506): 537-541
  CrossrefPubMedGoogle Scholar
• 15 Hoadley KA, Yau C, Wolf DM. , et al; Cancer Genome Atlas Research Network. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 2014; 158 (04) 929-944
  CrossrefPubMedGoogle Scholar
• 16 Pajtler KW, Witt H, Sill M. , et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 2015; 27 (05) 728-743
  CrossrefPubMedGoogle Scholar
• 17 Wani K, Armstrong TS, Vera-Bolanos E. , et al; Collaborative Ependymoma Research Network. A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 2012; 123 (05) 727-738
  CrossrefPubMedGoogle Scholar
• 18 Witt H, Mack SC, Ryzhova M. , et al. Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 2011; 20 (02) 143-157
  CrossrefPubMedGoogle Scholar
• 19 Mack SC, Witt H, Piro RM. , et al. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 2014; 506 (7489): 445-450
  CrossrefPubMedGoogle Scholar
• 20 Panwalkar P, Clark J, Ramaswamy V. , et al. Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. Acta Neuropathol 2017; 134 (05) 705-714
  CrossrefPubMedGoogle Scholar
• 21 Gessi M, Capper D, Sahm F. , et al. Evidence of H3 K27M mutations in posterior fossa ependymomas. Acta Neuropathol 2016; 132 (04) 635-637
  CrossrefPubMedGoogle Scholar
• 22 Ryall S, Guzman M, Elbabaa SK. , et al. H3 K27M mutations are extremely rare in posterior fossa group A ependymoma. Childs Nerv Syst 2017; 33 (07) 1047-1051
  CrossrefPubMedGoogle Scholar
• 23 Warmuth-Metz M. Imaging and Diagnosis in Pediatric Brain Tumor Studies. Cham, Switzerland: Springer; 2017
  Google Scholar
• 24 Bagley CA, Kothbauer KF, Wilson S, Bookland MJ, Epstein FJ, Jallo GI. Resection of myxopapillary ependymomas in children. J Neurosurg 2007; 106 (4, Suppl): 261-267
  PubMedGoogle Scholar
• 25 Pajtler KW, Mack SC, Ramaswamy V. , et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol 2017; 133 (01) 5-12
  CrossrefPubMedGoogle Scholar
• 26 Bouffet E, Foreman N. Chemotherapy for intracranial ependymomas. Childs Nerv Syst 1999; 15 (10) 563-570
  CrossrefPubMedGoogle Scholar
• 27 Gramatzki D, Roth P, Felsberg J. , et al. Chemotherapy for intracranial ependymoma in adults. BMC Cancer 2016; 16: 287
  CrossrefPubMedGoogle Scholar
• 28 Nuño M, Yu JJ, Varshneya K. , et al. Treatment and survival of supratentorial and posterior fossa ependymomas in adults. J Clin Neurosci 2016; 28: 24-30
  CrossrefPubMedGoogle Scholar
• 29 Bouffet E, Perilongo G, Canete A, Massimino M. Intracranial ependymomas in children: a critical review of prognostic factors and a plea for cooperation. Med Pediatr Oncol 1998; 30 (06) 319-329 , discussion 329–331
  CrossrefPubMedGoogle Scholar
• 30 Cage TA, Clark AJ, Aranda D. , et al. A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediatr 2013; 11 (06) 673-681
  CrossrefPubMedGoogle Scholar
• 31 Merchant TE. Current clinical challenges in childhood ependymoma: a focused review. J Clin Oncol 2017; 35 (21) 2364-2369
  CrossrefPubMedGoogle Scholar
• 32 Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 2009; 10 (03) 258-266
  CrossrefPubMedGoogle Scholar
• 33 Macdonald SM, Sethi R, Lavally B. , et al. Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients. Neuro-oncol 2013; 15 (11) 1552-1559
  CrossrefPubMedGoogle Scholar
• 34 Conklin HM, Li C, Xiong X, Ogg RJ, Merchant TE. Predicting change in academic abilities after conformal radiation therapy for localized ependymoma. J Clin Oncol 2008; 26 (24) 3965-3970
  CrossrefPubMedGoogle Scholar
• 35 Di Pinto M, Conklin HM, Li C, Xiong X, Merchant TE. Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma. Int J Radiat Oncol Biol Phys 2010; 77 (04) 1002-1008
  CrossrefPubMedGoogle Scholar
• 36 Netson KL, Conklin HM, Wu S, Xiong X, Merchant TE. A 5-year investigation of children's adaptive functioning following conformal radiation therapy for localized ependymoma. Int J Radiat Oncol Biol Phys 2012; 84 (01) 217-223.e1
  CrossrefPubMedGoogle Scholar
• 37 Willard VW, Conklin HM, Boop FA, Wu S, Merchant TE. Emotional and behavioral functioning after conformal radiation therapy for pediatric ependymoma. Int J Radiat Oncol Biol Phys 2014; 88 (04) 814-821
  CrossrefPubMedGoogle Scholar
• 38 Benesch M, Frappaz D, Massimino M. Spinal cord ependymomas in children and adolescents. Childs Nerv Syst 2012; 28 (12) 2017-2028
  CrossrefPubMedGoogle Scholar
• 39 Akyurek S, Chang EL, Yu TK. , et al. Spinal myxopapillary ependymoma outcomes in patients treated with surgery and radiotherapy at M.D. Anderson Cancer Center. J Neurooncol 2006; 80 (02) 177-183
  CrossrefPubMedGoogle Scholar
• 40 Bagley CA, Wilson S, Kothbauer KF, Bookland MJ, Epstein F, Jallo GI. Long term outcomes following surgical resection of myxopapillary ependymomas. Neurosurg Rev 2009; 32 (03) 321-334 , discussion 334
  CrossrefPubMedGoogle Scholar
• 41 Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D. Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst 2010; 26 (07) 905-911
  CrossrefPubMedGoogle Scholar
• 42 Bouffet E, Hawkins CE, Ballourah W. , et al. Survival benefit for pediatric patients with recurrent ependymoma treated with reirradiation. Int J Radiat Oncol Biol Phys 2012; 83 (05) 1541-1548
  CrossrefPubMedGoogle Scholar
• 43 Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys 2008; 71 (01) 87-97
  CrossrefPubMedGoogle Scholar
• 44 Ramaswamy V, Hielscher T, Mack SC. , et al. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis. J Clin Oncol 2016; 34 (21) 2468-2477
  CrossrefPubMedGoogle Scholar
• 45 Good CD, Wade AM, Hayward RD. , et al. Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?. J Neurosurg 2001; 94 (01) 27-32
  CrossrefPubMedGoogle Scholar
• 46 Lundar T, Due-Tønnessen BJ, Scheie D, Brandal P. Pediatric spinal ependymomas: an unpredictable and puzzling disease. Long-term follow-up of a single consecutive institutional series of ten patients. Childs Nerv Syst 2014; 30 (12) 2083-2088
  CrossrefPubMedGoogle Scholar
• 47 Gojo J, Lötsch D, Spiegl-Kreinecker S. , et al. Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain. Neuro-oncol 2017; 19 (09) 1183-1194
  PubMedGoogle Scholar
• 48 Korshunov A, Witt H, Hielscher T. , et al. Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 2010; 28 (19) 3182-3190
  CrossrefPubMedGoogle Scholar
• 49 Tzaridis T, Milde T, Pajtler KW. , et al. Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma. Oncotarget 2016; 7 (38) 61860-61873
  PubMedGoogle Scholar
• 50 Brügger F, Dettmer MS, Neuenschwander M, Perren A, Marinoni I, Hewer E. TERT promoter mutations but not the alternative lengthening of telomeres phenotype are present in a subset of ependymomas and are associated with adult onset and progression to ependymosarcoma. J Neuropathol Exp Neurol 2017; 76 (01) 61-66
  PubMedGoogle Scholar
• 51 Barszczyk M, Buczkowicz P, Castelo-Branco P. , et al. Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells. Acta Neuropathol 2014; 128 (06) 863-877
  CrossrefPubMedGoogle Scholar
• 52 Chen C, Chen L, Yao Y, Qin Z, Chen H. Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: a multifactorial analysis of 176 patients. J Neurooncol 2016; 127 (01) 43-52
  CrossrefPubMedGoogle Scholar
• 53 Rajeshwari M, Sharma MC, Kakkar A. , et al. Evaluation of chromosome 1q gain in intracranial ependymomas. J Neurooncol 2016; 127 (02) 271-278
  CrossrefPubMedGoogle Scholar
• 54 Reni M, Brandes AA, Vavassori V. , et al. A multicenter study of the prognosis and treatment of adult brain ependymal tumors. Cancer 2004; 100 (06) 1221-1229
  CrossrefPubMedGoogle Scholar
• 55 Metellus P, Barrie M, Figarella-Branger D. , 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): 1338-1349
  CrossrefPubMedGoogle Scholar
• 56 Burkhardt B, Moericke A, Klapper W. , et al. Pediatric precursor T lymphoblastic leukemia and lymphoblastic lymphoma: differences in the common regions with loss of heterozygosity at chromosome 6q and their prognostic impact. Leuk Lymphoma 2008; 49 (03) 451-461
  CrossrefPubMedGoogle Scholar
• 57 Armstrong TS, Vera-Bolanos E, Bekele BN, Aldape K, Gilbert MR. Adult ependymal tumors: prognosis and the M. D. Anderson Cancer Center experience. Neuro-oncol 2010; 12 (08) 862-870
  PubMedGoogle Scholar
• 58 Weber DC, Wang Y, Miller R. , et al. Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network. Neuro-oncol 2015; 17 (04) 588-595
  PubMedGoogle Scholar
• 59 Armstrong TS, Vera-Bolanos E, Gilbert MR. Clinical course of adult patients with ependymoma: results of the Adult Ependymoma Outcomes Project. Cancer 2011; 117 (22) 5133-5141
  CrossrefPubMedGoogle Scholar
• 60 Walbert T, Mendoza TR, Vera-Bolaños 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 Neurooncol 2015; 121 (02) 341-348
  CrossrefPubMedGoogle Scholar
• 61 Viereck MJ, Ghobrial GM, Beygi S, Harrop JS. Improved patient quality of life following intradural extramedullary spinal tumor resection. J Neurosurg Spine 2016; 25 (05) 640-645
  CrossrefPubMedGoogle Scholar
• 62 Xiao R, Miller JA, Abdullah KG, Lubelski D, Mroz TE, Benzel EC. Quality of life outcomes following resection of adult intramedullary spinal cord tumors. Neurosurgery 2016; 78 (06) 821-828
  CrossrefPubMedGoogle Scholar
• 63 Murai T, Sato K, Iwabuchi M. , et al. Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy. Jpn J Radiol 2016; 34 (03) 211-218
  CrossrefPubMedGoogle Scholar
• 64 Brandes AA, Cavallo G, Reni M. , 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 (01) 143-148
  CrossrefPubMedGoogle Scholar
• 65 Rudà R, Bosa C, Magistrello M. , et al. Temozolomide as salvage treatment for recurrent intracranial ependymomas of the adult: a retrospective study. Neuro-oncol 2016; 18 (02) 261-268
  PubMedGoogle Scholar
• 66 Green RM, Cloughesy TF, Stupp R. , et al. Bevacizumab for recurrent ependymoma. Neurology 2009; 73 (20) 1677-1680
  CrossrefPubMedGoogle Scholar
• 67 Morris KA, Afridi SK, Evans DG. , et al; on behalf of the UK NF2 Research Group. The response of spinal cord ependymomas to bevacizumab in patients with neurofibromatosis type 2. J Neurosurg Spine 2017; 26 (04) 474-482
  CrossrefPubMedGoogle Scholar
• 68 Wright KD, Daryani VM, Turner DC. , et al. Phase I study of 5-fluorouracil in children and young adults with recurrent ependymoma. Neuro-oncol 2015; 17 (12) 1620-1627
  PubMedGoogle Scholar