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Outcomes following management of relapsed pediatric posterior fossa ependymoma in the molecular era

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A Correction to this article was published on 28 April 2023

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Abstract

Purpose

The overall survival and prognostic factors for children with multiply recurrent posterior fossa ependymoma are not well understood. We aimed to assess prognostic factors associated with survival for relapsed pediatric posterior fossa ependymoma.

Methods

An institutional database was queried for children with a primary diagnosis of posterior fossa ependymoma from 2000 to 2019. Kaplan–Meier survival analysis and Cox-proportional hazard regression were used to assess the relationship between treatment factors and overall survival.

Results

There were 60 patients identified; molecular subtype was available for 56, of which 49 (87.5%) were PF-A and 7 (12.5%) were PF-B. Relapse occurred in 29 patients (48%) at a mean time of 24 months following primary resection. Median 50% survival was 12.3 years for all patients and 3.3 years following diagnosis of first relapsed disease. GTR was associated with significantly improved survival following primary resection (HR 0.373, 95% CI 0.14–0.96). Presence of recurrent disease was significantly associated with worse survival (p < 0.0001). At recurrent disease diagnosis, disseminated disease was a negative prognostic factor (HR 11.0 95% CI 2.7–44) while GTR at first relapse was associated with improved survival HR 0.215 (95% CI: 0.048–0.96, p = 0.044). Beyond first relapse, the impact of GTR was not significant on survival, though surgery compared to no surgery was favorable with HR 0.155 (95% CI: 0.04–0.59).

Conclusions

Disseminated disease at recurrence and extent of resection for first relapsed disease were important prognostic factors. Surgery compared to no surgery was associated with improved survival for the multiply recurrent ependymoma cohort.

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Data Availability

Data was obtained following approval by our institutional research ethics board. Data may be available upon reasonable request by qualified investigators provided appropriate institutional approval is obtained.

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References

  1. McGuire CS, Sainani KL, Fisher PG (2009) Incidence patterns for ependymoma: a surveillance, epidemiology, and end results study. J Neurosurg 110(4):725–729

    Article  PubMed  Google Scholar 

  2. Lundar T, Due-Tønnessen BJ, Frič R, Brandal P, Due-Tønnessen P (2020) Adult outcome after treatment of pediatric posterior fossa ependymoma: long-term follow-up of a single consecutive institutional series of 22 patients with more than 5 years of survival. J Neurosurg Pediatr. https://doi.org/10.3171/2020.1.PEDS19700

    Article  PubMed  Google Scholar 

  3. Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ et al (2020) A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival and ineffectiveness of current treatments across central nervous system locations and molecular subgroups. Pediatr Blood Cancer 67(9):e28426

    Article  CAS  PubMed  Google Scholar 

  4. Timmermann B, Kortmann RD, Kühl J, Meisner C, Slavc I, Pietsch T et al (2000) Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials HIT 88/89 and HIT 91. Int J Radiat Oncol Biol Phys 46(2):287–295

    Article  CAS  PubMed  Google Scholar 

  5. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820

    Article  PubMed  Google Scholar 

  6. Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F et al (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27(5):728–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cage TA, Clark AJ, Aranda D, Gupta N, Sun PP, Parsa AT et al (2013) A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediatr 11(6):673–681

    Article  PubMed  Google Scholar 

  8. Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW et al (2016) Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis. J Clin Oncol 34(21):2468–2477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10(3):258–266

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rogers L, Pueschel J, Spetzler R, Shapiro W, Coons S, Thomas T et al (2005) Is gross-total resection sufficient treatment for posterior fossa ependymomas? J Neurosurg 102(4):629–636

    Article  PubMed  Google Scholar 

  11. Merchant TE, Bendel AE, Sabin ND, Burger PC, Shaw DW, Chang E et al (2019) Conformal radiation therapy for pediatric ependymoma, chemotherapy for incompletely resected ependymoma, and observation for completely resected. Supratentorial Ependymoma J Clin Oncol 37(12):974–983

    Article  CAS  PubMed  Google Scholar 

  12. Khatua S, Ramaswamy V, Bouffet E (2017) Current therapy and the evolving molecular landscape of paediatric ependymoma. Eur J Cancer 70:34–41

    Article  CAS  PubMed  Google Scholar 

  13. Merchant TE, Boop FA, Kun LE, Sanford RA (2008) A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys 71(1):87–97

    Article  PubMed  Google Scholar 

  14. Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D (2010) Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst 26(7):905–911

    Article  PubMed  Google Scholar 

  15. Rudà R, Reifenberger G, Frappaz D, Pfister SM, Laprie A, Santarius T et al (2018) EANO guidelines for the diagnosis and treatment of ependymal tumors. Neuro Oncol 20(4):445–456

    Article  PubMed  Google Scholar 

  16. Tamburrini G, D’Ercole M, Pettorini BL, Caldarelli M, Massimi L, Di Rocco C (2009) Survival following treatment for intracranial ependymoma: a review. Childs Nerv Syst 25(10):1303–1312

    Article  CAS  PubMed  Google Scholar 

  17. Liu ZM, Han Z, Wang JM, Sun T, Liu W, Li B et al (2022) Treatment and outcome of pediatric intracranial ependymoma after first relapse. J Neurooncol 157(3):385–396

    Article  CAS  PubMed  Google Scholar 

  18. Adolph JE, Fleischhack G, Gaab C, Mikasch R, Mynarek M, Rutkowski S et al (2021) Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies. J Neurooncol 155(2):193–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tsang DS, Murray L, Ramaswamy V, Zapotocky M, Tabori U, Bartels U et al (2019) Craniospinal irradiation as part of re-irradiation for children with recurrent intracranial ependymoma. Neuro Oncol 21(4):547–557

    Article  CAS  PubMed  Google Scholar 

  20. Zapotocky M, Beera K, Adamski J, Laperierre N, Guger S, Janzen L et al (2019) Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: cure at a cost. Cancer 125(11):1867–1876

    Article  CAS  PubMed  Google Scholar 

  21. Adolph JE, Fleischhack G, Mikasch R, Zeller J, Warmuth-Metz M, Bison B et al (2021) Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study. Neuro Oncol 23(6):1012–1023

    Article  CAS  PubMed  Google Scholar 

  22. Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R et al (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20(2):143–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Montgomery E, Thirunavu V, Shlobin N, Lam S, DeCuypere M (2022) EPEN-17 recurrent infratentorial ependymomas in children: a meta-analysis on molecular-based outcomes. Neuro Oncol. https://doi.org/10.1093/neuonc/noac079.154

    Article  Google Scholar 

  24. Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M et al (2018) Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathol 136(2):227–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lassaletta A, Bouffet E, Mabbott D, Kulkarni AV (2015) Functional and neuropsychological late outcomes in posterior fossa tumors in children. Childs Nerv Syst 31(10):1877–1890

    Article  PubMed  Google Scholar 

  26. Merchant TE, Pollack IF, Loeffler JS (2010) Brain tumors across the age spectrum: biology, therapy, and late effects. Semin Radiat Oncol 20(1):58–66

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mabbott DJ, Spiegler BJ, Greenberg ML, Rutka JT, Hyder DJ, Bouffet E (2005) Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J Clin Oncol 23(10):2256–2263

    Article  PubMed  Google Scholar 

  28. Upadhyaya SA, Robinson GW, Onar-Thomas A, Orr BA, Billups CA, Bowers DC et al (2019) Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial. Neuro Oncol 21(10):1319–1330

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ducassou A, Padovani L, Chaltiel L, Bolle S, Habrand JL, Claude L et al (2018) Pediatric localized intracranial ependymomas: a multicenter analysis of the société française de lutte contre les cancers de l’Enfant (SFCE) from 2000 to 2013. Int J Radiat Oncol Biol Phys 102(1):166–173

    Article  PubMed  Google Scholar 

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Funding

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Authors and Affiliations

  1. Division of Neurosurgery, University of Toronto, Toronto, ON, Canada

    Armaan K. Malhotra

  2. Neuro-oncology Section, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada

    Liana F. Nobre & Vijay Ramaswamy

  3. Division of Pediatric Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada

    George M. Ibrahim, Abhaya V. Kulkarni, James M. Drake, James T. Rutka, Michael D. Taylor & Peter B. Dirks

  4. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Eric Bouffet & Derek Tsang

  5. Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Michael C. Dewan

Authors
  1. Armaan K. Malhotra
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  2. Liana F. Nobre
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Contributions

Malhotra AK - Data collection, analysis, writing Nobre LF - Manuscript editing, figure creation, analysis Ibrahim GM - Manuscript editing, revisions Kulkarni AV - Manuscript editing, revisions Drake JM - Manuscript editing, revisions Rutka JT - Manuscript editing, revisions Bouffet E - Manuscript editing, revisions Taylor MD - Manuscript editing, revisions Tsang D - Manuscript editing, revisions Ramaswamy V - Manuscript editing, conception, figure design, revisions Dirks PB - Manuscript editing, conception, figure design, revisions Dewan MC - Data collection, manuscript drafting, editing, conception, figure design, revisions

Corresponding author

Correspondence to Michael C. Dewan.

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The original version of this article has been revised: The authors' names have been corrected.

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Malhotra, A.K., Nobre, L.F., Ibrahim, G.M. et al. Outcomes following management of relapsed pediatric posterior fossa ependymoma in the molecular era. J Neurooncol 161, 573–582 (2023). https://doi.org/10.1007/s11060-023-04258-x

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