Rahmi Atıl AKSOY, Yasemin ŞENGÜN, Melek Gamze AKSU, Elif GÜLER, Saim KAZAN, Mine GENÇ

Gross Total Resection of Childhood Intracranial Ependymoma is a Critically Important Factor in Survival

OBJECTIVE This study aimed to evaluate the effect of prognostic factors and treatment on survival in childhood intracranial ependymoma. METHODS In the past two decades, 28 patients with pediatric intracranial ependymoma who received postop erative radiotherapy in our institute were evaluated statistically in terms of prognostic factors and sur vival. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Possible prognostic factors, such as sex, histopathological grade, the extent of resection, tumor location, spinal metastasis, and chemotherapy were also analyzed by log-rank test. RESULTS Median age at diagnosis was 4 years (range, 1-17 years). Eighteen patients had infratentorial tumor, and 19 patients had Grade III tumor. Gross total resections (GTRs) were performed in 16 patients. The median clinical follow-up time was 66.9 months (range, 8-253 months). The estimated 5-year PFS and OS rates are 38% and 55%, respectively. The extent of resection was found the only prognostic factor associated with improved PFS and OS. Other factors, such as gender, histopathological grade, tumor location, spinal metastasis, and chemotherapy, showed no statistically significant effect on sur vival outcomes. CONCLUSION A multidisciplinary approach is required in the management of pediatric intracranial ependymomas. GTR is a crucial prognostic factor on survival. The lack of aggressive salvage treatments may result in worse survival. Future trials are needed to investigate molecular classification and individualized treat ment algorithms.

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1. Vitanza NA, Partap S. Pediatric ependymoma. J Child Neurol 2016;31(12):1354–66.
2. Neumann JE, Spohn M, Obrecht D, Mynarek M, Thomas C, Hasselblatt M, et al. Molecular character ization of histopathological ependymoma variants. Acta Neuropathol 2020;139(2):305–18.
3. Kilday JP, Rahman R, Dyer S, Ridley L, Lowe J, Coyle B, et al. Pediatric ependymoma: Biological perspec tives. Mol Cancer Res 2009;7(6):765–86.
4. Gerstner ER, Pajtler KW. Ependymoma. Semin Neurol 2018;38(1):104–11.
5. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neu ropathol 2016;131(6):803–20.
6. 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.
7. Pajtler KW, Mack SC, Ramaswamy V, Smith CA, Witt H, Smith A, et al. The current consensus on the clin ical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol 2017;133(1):5–12.
8. Toescu SM, Aquilina K. Current and emerging meth ods of management of ependymoma. Curr Oncol Rep 2019;21(9):78.
9. Rudà R, Reifenberger G, Frappaz D, Pfister SM, Laprie A, Santarius T, et al. EANO guidelines for the diagno sis and treatment of ependymal tumors. Neuro Oncol 2018;20(4):445–56.
10.Rousseau P, Habrand JL, Sarrazin D, Kalifa C, Terri er-Lacombe MJ, Rekacewicz C, et al. Treatment of intracranial ependymomas of children: Review of a 15-year experience. Int J Radiat Oncol Biol Phys. 1994;28(2):381–6.
11.Pollack IF, Gerszten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, et al. Intracranial ependymomas of childhood: Long-term outcome and prognostic fac tors. Neurosurgery 1995;37(4):655–66.
12.Perilongo G, Massimino M, Sotti G, Belfontali T, Masiero L, Rigobello L, et al. Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian pediatric neuro-oncology group. Med Pediatr Oncol. 1997;29(2):79–85.
13.Nazar GB, Hoffman HJ, Becker LE, Jenkin D, Humphreys RP, Hendrick EB. Infratentorial ependy momas in childhood: Prognostic factors and treat ment. J Neurosurg 1990;72(3):408–17.
14.Merchant TE, Li C, Xiong X, Kun LE, Boop FA, San- ford RA. Conformal radiotherapy after surgery for paediatric ependymoma: A prospective study. Lancet Oncol 2009;10(3):258–66.
15.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 Ra diat Oncol Biol Phys 2005;61(2):387–91.
16.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 J Clin Oncol 2002;25(2):117–22.
17.Robertson PL, Zeltzer PM, Boyett JM, Rorke LB, Allen JC, Geyer JR, et al. Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: A report of the children’s cancer group. J Neurosurg 1998;88(4):695–703.
18.Massimino M, Gandola L, Giangaspero F, Sandri A, Valagussa P, Perilongo G, et al. Hyperfraction ated radiotherapy and chemotherapy for childhood ependymoma: Final results of the first prospective AIEOP (Associazione Italiana di Ematologia-On cologia Pediatrica) study. Int J Radiat Oncol Biol Phys 2004;58(5):1336–45.
19.Massimino M, Miceli R, Giangaspero F, Boschetti L, Modena P, Antonelli M, et al. Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. Neuro Oncol 2016;18(10):1451–60.
20.Agaoglu FY, Ayan I, Dizdar Y, Kebudi R, Gorgun O, Darendeliler E. Ependymal tumors in childhood. Pe diatr Blood Cancer 2005;45(3):298–303.
21.Khatua S, Mangum R, Bertrand KC, Zaky W, McCall D, Mack SC. Pediatric ependymoma: Current treat ment and newer therapeutic insights. Future Oncol 2018;14(30):3175–86.
22.Hübner JM, Kool M, Pfister SM, Pajtler KW. Epidemi ology, molecular classification and WHO grading of ependymoma. J Neurosurg Sci 2018;62(1):46–50.
23.Mack SC, Pajtler KW, Chavez L, Okonechnikov K, Bertrand KC, Wang X, et al. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling. Nature 2018;553(7686):101–5.
24.Vaidya K, Smee R, Williams JR. Prognostic factors and treatment options for paediatric ependymomas. J Clin Neurosci 2012;19(9):1228–35.
25.Grill J, Le Deley MC, Gambarelli D, Raquin MA, Couanet D, Pierre-Kahn A, et al. Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: A multicenter trial of the French society of pediatric oncology. J Clin Oncol 2001;19(5):1288–96.
26.Hammad M, Hosny M, Khalil EM, Alfaar AS, Fawzy M. Pediatric ependymoma: A single-center expe rience from a developing country. Indian J Cancer 2021;58(3):378–86.
27.Tashvighi M, Mehrvar A, Hedayati Asl AA, Mehrvar N, Ghorbani R, Naderi A, et al. Treatment challenges and outcomes for pediatric intracranial ependymoma at a single institution in Iran. Pediatr Hematol Oncol 2018;35(1):60–75.
28.Marinoff AE, Ma C, Guo D, Snuderl M, Wright KD, Manley PE, et al. Rethinking childhood ependy moma: A retrospective, multi-center analysis re veals poor long-term overall survival. J Neurooncol 2017;135(1):201–11.
29.ClinicalTrials.gov: NCT02265770: An Interna tional Clinical Program for the Diagnosis and Treat ment of Children with Ependymoma (SIOP-EP-II). Available at: https://clinicaltrials.gov/ct2/show/ NCT02265770?term=nct02265770&rank=1
30.Merchant TE, Bendel AE, Sabin ND, Burger PC, Shaw DW, Chang E, et al. Conformal radiation therapy for pediatric ependymoma, chemotherapy for incom pletely resected ependymoma, and observation for completely resected, supratentorial ependymoma. J Clin Oncol 2019;37(12):974–83.
31.ClinicalTrials.gov: NCT01096368: Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients with Newly Diagnosed Ependy moma. Available at: https://clinicaltrials.gov/ct2/ show/NCT01096368?term=nct01096368 &rank=1. Accessed Nov 15, 2021.