Advertisement

Journal of Neuro-Oncology

, Volume 113, Issue 2, pp 285–291 | Cite as

Outcome of infants and young children with newly diagnosed ependymoma treated on the “Head Start” III prospective clinical trial

  • Rajkumar Venkatramani
  • Lingyun Ji
  • Joseph Lasky
  • Kelley Haley
  • Alexander Judkins
  • Shengmei Zhou
  • Richard Sposto
  • Randal Olshefski
  • James Garvin
  • Tanya Tekautz
  • Gloria Kennedy
  • Shahrad Rod Rassekh
  • Theodore Moore
  • Sharon Gardner
  • Jeffrey Allen
  • Richard Shore
  • Christopher Moertel
  • Mark Atlas
  • Girish Dhall
  • Jonathan Finlay
Clinical Study

Abstract

This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational “Head Start” III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR. Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 ± 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 ± 13 % and 73 ± 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation.

Keywords

Ependymoma Supratentorial Infratentorial Irradiation Surgery 

Notes

Conflict of interest

None.

Funding

Alex’s Lemonade Stand Foundation; Pediatric Cancer Research Foundation; Soccer for Hope Foundation; Isabella Grace Jordan Fund.

References

  1. 1.
    Zacharoulis S, Moreno L (2009) Ependymoma: an update. J of Child Neurol 24:1431–1438CrossRefGoogle Scholar
  2. 2.
    Merchant TE, Li C, Xiong X et al (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10:258–266PubMedCrossRefGoogle Scholar
  3. 3.
    Grill J, Le Deley M-C, Gambarelli D 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
  4. 4.
    Grundy RG, Wilne SA, Weston CL et al (2007) Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol 8:696–705PubMedCrossRefGoogle Scholar
  5. 5.
    Zacharoulis S, Levy A, Chi SN 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 49:34–40PubMedCrossRefGoogle Scholar
  6. 6.
    Perilongo G, Massimino M, Sotti G et al (1997) Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group. Med Pediatr Oncol 29:79–85PubMedCrossRefGoogle Scholar
  7. 7.
    Pollack IF, Gerszten PC, Martinez AJ et al (1995) Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37:655–666 (Discussion 666–667)PubMedCrossRefGoogle Scholar
  8. 8.
    Andreiuolo F, Puget S, Peyre M et al (2010) Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12:1126–1134PubMedCrossRefGoogle Scholar
  9. 9.
    Schneider D, Monoranu C-M, Huang B et al (2009) Pediatric supratentorial ependymomas show more frequent deletions on chromosome 9 than infratentorial ependymomas: a microsatellite analysis. Cancer Genet Cytogenet 191:90–96PubMedCrossRefGoogle Scholar
  10. 10.
    Taylor MD, Poppleton H, Fuller C et al (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335PubMedCrossRefGoogle Scholar
  11. 11.
    Hukin J, Epstein F, Lefton D, Allen J (1998) Treatment of intracranial ependymoma by surgery alone. Pediatr Neurosurg 29:40–45PubMedCrossRefGoogle Scholar
  12. 12.
    Palma L, Celli P, Mariottini A, Zalaffi A, Schettini G (2000) The importance of surgery in supratentorial ependymomas. Child’s Nerv Syst 16:170–175CrossRefGoogle Scholar
  13. 13.
    Venkatramani R, Dhall G, Patel M et al (2012) Supratentorial ependymoma in children: to observe or to treat following gross total resection? Pediatr Blood Cancer 58:380–383PubMedCrossRefGoogle Scholar
  14. 14.
    McGuire CS, Sainani KL, Fisher PG (2009) Both location and age predict survival in ependymoma: a SEER study. Pediatr Blood Cancer 52:65–69PubMedCrossRefGoogle Scholar
  15. 15.
    Robertson PL, Zeltzer PM, Boyett JM et al (1998) Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children’s Cancer Group. J Neurosurg 88:695–703PubMedCrossRefGoogle Scholar
  16. 16.
    Horn B, Heideman R, Geyer R et al (1999) A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21:203–211PubMedCrossRefGoogle Scholar
  17. 17.
    Ellison DW, Kocak M, Figarella-Branger D et al (2011) Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 10:7PubMedCrossRefGoogle Scholar
  18. 18.
    Garvin JH Jr, Selch mt, Holmes E et al (2012) Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children’s Cancer Group protocol 9942: a report from the Children’s Oncology Group. Pediatr Blood Cancer 59:1183–1189PubMedCrossRefGoogle Scholar
  19. 19.
    Duffner PK, Horowitz ME, Krischer JP et al (1999) The treatment of malignant brain tumors in infants and very young children: an update of the Pediatric Oncology Group experience. Neuro oncol 1:152–161PubMedGoogle Scholar
  20. 20.
    Di Pinto M, Conklin HM, Li C, Xiong X, Merchant TE (2010) Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma. Int J Radiat Oncol Bio Phys 77:1002–1008CrossRefGoogle Scholar
  21. 21.
    Netson KL, Conklin HM, Wu S, Xiong X, Merchant TE (2012) A 5-year investigation of children’s adaptive functioning following conformal radiation therapy for localized ependymoma. Int J Radiat Oncol Bio Phys 84:217–223CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rajkumar Venkatramani
    • 1
  • Lingyun Ji
    • 2
  • Joseph Lasky
    • 3
  • Kelley Haley
    • 1
  • Alexander Judkins
    • 14
  • Shengmei Zhou
    • 14
  • Richard Sposto
    • 1
  • Randal Olshefski
    • 4
  • James Garvin
    • 5
  • Tanya Tekautz
    • 6
  • Gloria Kennedy
    • 7
  • Shahrad Rod Rassekh
    • 8
  • Theodore Moore
    • 9
  • Sharon Gardner
    • 10
  • Jeffrey Allen
    • 10
  • Richard Shore
    • 11
  • Christopher Moertel
    • 12
  • Mark Atlas
    • 13
  • Girish Dhall
    • 1
  • Jonathan Finlay
    • 1
  1. 1.Division of Hematology/OncologyChildren’s Hospital Los AngelesLos AngelesUSA
  2. 2.University of Southern CaliforniaLos AngelesUSA
  3. 3.Harbor-UCLA Medical CenterTorranceUSA
  4. 4.Nationwide Children’s HospitalColumbusUSA
  5. 5.Columbia-PresbyterianNew YorkUSA
  6. 6.Cleveland ClinicClevelandUSA
  7. 7.SUNY UpstateSyracuseUSA
  8. 8.British Columbia’s Children’s HospitalVancouverCanada
  9. 9.Mattel Children’s Hospital at UCLALos AngelesUSA
  10. 10.New York Langone Medical CenterNew YorkUSA
  11. 11.Children’s Mercy HospitalKansas CityUSA
  12. 12.University of MinnesotaMinneapolisUSA
  13. 13.Schneider Children’sNew Hyde ParkUSA
  14. 14.Children’s Hospital Los AngelesLos AngelesUSA

Personalised recommendations