Advertisement

Child's Nervous System

, Volume 26, Issue 7, pp 905–911 | Cite as

Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis

  • Stergios Zacharoulis
  • Sue Ashley
  • Lucas Moreno
  • Jean-Claude Gentet
  • Maura Massimino
  • Didier Frappaz
Original Paper

Abstract

Introduction

More than a third of children with ependymoma experience relapse, and despite multimodal treatment, less than 25% of them can then achieve long-term survival. Prognostic factors for patients who relapse have not been extensively analyzed.

Patients and methods

We retrospectively analyzed 82 patients from four pediatric oncology European institutions in order to identify prognostic factors and influence of treatment modalities in relapsed ependymoma.

Results

First relapse occurred after a median of 19 months (1 month–16 years). Five-year progression-free survival and overall survival of the cohort were 17% and 27.6%, respectively. Survival was statistically significantly higher for patients achieving gross total resection. No survival benefit was seen for children receiving chemotherapy whereas patients who were amenable to some form of re-irradiation had a better outcome. Objective responses were found in more than 25% of patients receiving oral etoposide, temozolomide, or vincristine/etoposide/cyclophosphamide regimens. Multivariate analysis confirmed that patients with mixed relapses, no surgery at relapse, and receiving chemotherapy did worse (hazard ratio = 3.6, 3.3, and 1.7, respectively, all p < 0.05).

Discussion

Relapsed ependymoma carries a very poor prognosis with an indolent chronic course, leading to death in approximately 90% of the patients. Complete surgical resection whenever possible should be encouraged. Radiation therapy of the relapsed lesions can provide some minor benefit whereas chemotherapy despite the occasional responses provides no benefit in the final outcome which is dismal. Efforts have to be orchestrated internationally to enroll these patients on clinical trials using biology-based therapies.

Keywords

Relapsed ependymoma Targeted therapies Re-irradiation 

References

  1. 1.
    Reni M, Gatta G, Mazza E, Vecht C (2007) Ependymoma. Crit Rev Oncol Hematol 63:81–89CrossRefPubMedGoogle Scholar
  2. 2.
    Zacharoulis S, Ji L, Pollack IF, Duffner P, Geyer R, Grill J et al (2008) Metastatic ependymoma: a multi-institutional retrospective analysis of prognostic factors. Pediatr Blood Cancer 50:231–235CrossRefPubMedGoogle Scholar
  3. 3.
    Merchant TE, Fouladi M (2005) Ependymoma: new therapeutic approaches including radiation and chemotherapy. J Neurooncol 75:287–299CrossRefPubMedGoogle Scholar
  4. 4.
    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 10:258–266CrossRefPubMedGoogle Scholar
  5. 5.
    Bouffet E, Perilongo G, Canete A, Massimino M (1998) Intracranial ependymomas in children: a critical review of prognostic factors and a plea for cooperation. Med Pediatr Oncol 30:319–329CrossRefPubMedGoogle Scholar
  6. 6.
    Duffner PK, Krischer JP, Sanford RA, Horowitz ME, Burger PC, Cohen ME et al (1998) Prognostic factors in infants and very young children with intracranial ependymomas. Pediatr Neurosurg 28:215–222CrossRefPubMedGoogle Scholar
  7. 7.
    Foreman NK, Love S, Gill SS, Coakham HB (1997) Second-look surgery for incompletely resected fourth ventricle ependymomas: technical case report. Neurosurgery 40:856–860CrossRefPubMedGoogle Scholar
  8. 8.
    Poltinnikov IM, Merchant TE (2006) CSF cytology has limited value in the evaluation of patients with ependymoma who have MRI evidence of metastasis. Pediatr Blood Cancer 47:169–173CrossRefPubMedGoogle Scholar
  9. 9.
    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 71:87–97PubMedGoogle Scholar
  10. 10.
    Messahel B, Ashley S, Saran F, Ellison D, Ironside J, Phipps K et al (2009) Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome. Eur J Cancer 45:1815–1823CrossRefPubMedGoogle Scholar
  11. 11.
    Mason WP, Goldman S, Yates AJ, Boyett J, Li H, Finlay JL (1998) Survival following intensive chemotherapy with bone marrow reconstitution for children with recurrent intracranial ependymoma—a report of the Children’s Cancer Group. J Neurooncol 37:135–143CrossRefPubMedGoogle Scholar
  12. 12.
    Needle MN, Goldwein JW, Grass J, Cnaan A, Bergman I, Molloy P et al (1997) Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood. Cancer 80:341–347CrossRefPubMedGoogle Scholar
  13. 13.
    Zacharoulis S, Levy A, Chi SN, Gardner S, Rosenblum M, Miller DC et al (2007) Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 49:34–40CrossRefPubMedGoogle Scholar
  14. 14.
    Grill J, Le Deley MC, Gambarelli D, Raquin MA, Couanet D, Pierre-Kahn A et al (2001) 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 19:1288–1296PubMedGoogle Scholar
  15. 15.
    Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J et al (2007) Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol 8:696–705CrossRefPubMedGoogle Scholar
  16. 16.
    Merchant TE, Mulhern RK, Krasin MJ, Kun LE, Williams T, Li C et al (2004) Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 22:3156–3162CrossRefPubMedGoogle Scholar
  17. 17.
    Bertolone SJ, Baum ES, Krivit W, Hammond GD (1989) A phase II study of cisplatin therapy in recurrent childhood brain tumors. A report from the Childrens Cancer Study Group. J Neurooncol 7:5–11CrossRefPubMedGoogle Scholar
  18. 18.
    Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D et al (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23:7621–7631CrossRefPubMedGoogle Scholar
  19. 19.
    Bouffet E, Foreman N (1999) Chemotherapy for intracranial ependymomas. Childs Nerv Syst 15:563–570CrossRefPubMedGoogle Scholar
  20. 20.
    Goldwein JW, Glauser TA, Packer RJ, Finlay JL, Sutton LN, Curran WJ et al (1990) Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors. Cancer 66:557–563CrossRefPubMedGoogle Scholar
  21. 21.
    Gornet MK, Buckner JC, Marks RS, Scheithauer BW, Erickson BJ (1999) Chemotherapy for advanced CNS ependymoma. J Neurooncol 45:61–67CrossRefPubMedGoogle Scholar
  22. 22.
    Bouffet E, Capra M, Bartels U (2009) Salvage chemotherapy for metastatic and recurrent ependymoma of childhood. Childs Nerv Syst 25(10):1293–1301CrossRefPubMedGoogle Scholar
  23. 23.
    Buccoliero AM, Castiglione F, Rossi DD, Paglierani M, Maio V, Gheri CF et al (2008) O6-Methylguanine-DNA-methyltransferase in recurring anaplastic ependymomas: PCR and immunohistochemistry. J Chemother 20:263–268PubMedGoogle Scholar
  24. 24.
    Combs SE, Thilmann C, Debus J, Schulz-Ertner D (2006) Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT). BMC Cancer 6:222CrossRefPubMedGoogle Scholar
  25. 25.
    Conklin HM, Li C, Xiong X, Ogg RJ, Merchant TE (2008) Predicting change in academic abilities after conformal radiation therapy for localized ependymoma. J Clin Oncol 26:3965–3970CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Stergios Zacharoulis
    • 1
  • Sue Ashley
    • 2
  • Lucas Moreno
    • 1
  • Jean-Claude Gentet
    • 3
  • Maura Massimino
    • 4
  • Didier Frappaz
    • 5
  1. 1.Department of PaediatricsThe Royal Marsden HospitalSuttonUK
  2. 2.BiostatisticsThe Royal Marsden HospitalSuttonUK
  3. 3.Hôpital de la TimoneMarseilleFrance
  4. 4.PediatricsNational Tumor InstituteMilanItaly
  5. 5.Institute d’Hémato-Oncologie PédiatriqueLyonFrance

Personalised recommendations