Advertisement

Neurocognitive, academic and functional outcomes in survivors of infant ependymoma (UKCCSG CNS 9204)

  • Matthew C. H. J. MorrallEmail author
  • Rosa Reed-Berendt
  • Kate Moss
  • Helen Stocks
  • Alexandra L. Houston
  • Poppy Siddell
  • Susan Picton
  • Richard Grundy
ORIGINAL ARTICLE

Abstract

Purpose

This is the first UK multi-centre case-controlled study with follow-up in excess of 10 years to report the neurocognitive, academic and psychological outcomes of individuals diagnosed with a brain tumour in early childhood. Children enrolled into the UKCCSG CNS 9204 trial, diagnosed with intracranial ependymoma when aged ≤ 36 months old, who received a primary chemotherapy strategy to defer or avoid radiotherapy, were recruited.

Methods

Outcomes of those who relapsed and subsequently received radiotherapy (n = 13) were compared to those enrolled who did not relapse (n = 16), age-matched controls—diagnosed with solid non-central nervous system (SN-CNS; n = 15) tumours or low-grade posterior fossa pilocytic astrocytoma (PFPA; n = 15), and normative data. Analyses compared nine neurocognitive outcomes as primary measures with quality of survival as secondary measures.

Results

Relapsed ependymoma participants performed significantly worse than their non-relapsed counterparts on measures of Full Scale IQ, Perceptual Reasoning, Word Reading and Numerical Operations. The relapsed ependymoma group performed significantly worse than SN-CNS controls on all primary measures, whereas non-relapsing participants only differed significantly from SN-CNS controls on measures of Processing Speed and General Memory. Relapsed ependymoma participants fared worse than all groups on measures of quality of survival.

Conclusions

The relapsed irradiated ependymoma group demonstrated the most significantly impaired neurocognitive outcomes at long-term follow-up. Non-relapsing participants demonstrated better outcomes than those who relapsed. Results tentatively suggest avoiding radiotherapy helped preserve neurocognitive and learning outcomes of individuals diagnosed with ependymoma when aged ≤ 36 months old. Prospective neurocognitive surveillance is required. Recommendations for clinical and research practice are provided.

Keywords

Brain tumour Ependymoma Paediatric Outcome Neurocognitive Quality of survival 

Notes

Acknowledgements

The authors would like to give their full thanks to all the participants and their families who consented to take part in this study, Candlelighters, Principal Investigators, Research Nurses, Data Managers, Trial Administrators, Dr. Bull, Prof. Kennedy, Mr. McShane and Dr. Phillips.

Funding

Candlelighters-Childhood cancer charity in Yorkshire provided funding. The sponsor had no role in the study design, conduct, data collection, data management, analysis, interpretation, preparation, review or approval of the report.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee at which the studies were conducted. Ethical approval was awarded by the National Research Ethical Service (08/H1311/92).

Informed consent

Informed consent was obtained from all parents/guardians of participants, along with each participant providing informed assent.

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

381_2018_4015_MOESM1_ESM.docx (20 kb)
Online Resource 1 (DOCX 20 kb)
381_2018_4015_MOESM2_ESM.docx (21 kb)
Online Resource 2 (DOCX 20 kb)

References

  1. 1.
    Children’s Cancer and Leukaemia Group 2008 Factsheet. Ependymoma. Available from: http://www.cclg.org.uk/dynamic_files/Ependymoma.pdf [Accessed August 2013]
  2. 2.
    Godfraind C, Kaczmarska JM, Kocak M, Dalton J, Wright KD, Sanford RA, Boop FA, Gajjar A, Merchant TE, Ellison DW (2012 Aug 1) Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol 124(2):247–257CrossRefGoogle Scholar
  3. 3.
    Childhood Cancer Research Group (CCRG), which houses the National Registry of Childhood Tumours Progress Report. (2012) Incidence and survival data. Available from: www.ncin.org.uk/view?rid=2133 [Accessed November 2017]
  4. 4.
    Aukema EJ, Caan MW, Oudhuis N, Majoie CB, Vos FM, Reneman L, Last BF, Grootenhuis MA, Schouten-van Meeteren AY (2009) White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors. Int J Radiat Oncol* Biol* Phys 74(3):837–843CrossRefGoogle Scholar
  5. 5.
    Grill J, Viguier D, Kieffer V, Bulteau C, Sainte-Rose C, Hartmann O, Kalifa C, Dellatolas G (2004) Critical risk factors for intellectual impairment in children with posterior fossa tumors: the role of cerebellar damage. J Neurosurg Pediatr 101(2):152–158CrossRefGoogle Scholar
  6. 6.
    Ajithkumar T, Price S, Horan G, Burke A, Jefferies S (2017 Feb 28) Prevention of radiotherapy-induced neurocognitive dysfunction in survivors of paediatric brain tumours: the potential role of modern imaging and radiotherapy techniques. Lancet Oncol 18(2):e91–e100Google Scholar
  7. 7.
    Zhang XW, Wu XY, Sheng XF, Wang Y, Gao HY, Xu L, Zhu YM (2016) Ependymoma diagnosis and treatment progress. Int J Clin Exp Med 9(8):15050–15057Google Scholar
  8. 8.
    Palmer SL, Glass JO, Li Y, Ogg R, Qaddoumi I, Armstrong GT, Wright K, Wetmore C, Broniscer A, Gajjar A, Reddick WE (2012) White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor. Neuro-Oncology 14(9):1185–1193CrossRefGoogle Scholar
  9. 9.
    UKCCSG (1993) Management of children aged less than 3 years with brain tumours: UKCCSG study CNS 9204Google Scholar
  10. 10.
    Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J, Cox T, Chong WK, Campbell RH, Bailey CC, Gattamaneni R (2007) Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol 8(8):696–705CrossRefGoogle Scholar
  11. 11.
    Massimino M, Gandola L, Barra S, Giangaspero F, Casali C, Potepan P, Di Rocco C, Nozza P, Collini P, Viscardi E, Bertin D Infant ependymoma in a 10-year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) experience with omitted or deferred radiotherapy. Int J Radiat Oncol* Biol* Phys 2011, 80(3):807–814Google Scholar
  12. 12.
    Grill J, Le Deley MC, Gambarelli D, Raquin MA, Couanet D, Pierre-Kahn A, Habrand JL, Doz F, Frappaz D, Gentet JC, Edan C (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(5):1288–1296CrossRefGoogle Scholar
  13. 13.
    Merchant TE, Mulhern RK, Krasin MJ, Kun LE, Williams T, Li C, Xiong X, Khan RB, Lustig RH, Boop FA, Sanford RA (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(15):3156–3162CrossRefGoogle Scholar
  14. 14.
    Merchant TE, Bendel AE, Sabin N, Burger PC, Wu S, Boyett JM (2015) A Phase II trial of conformal radiation therapy for pediatric patients with localized ependymoma, chemotherapy prior to second surgery for incompletely resected ependymoma and observation for completely resected, differentiated, supratentorial ependymoma. Int J Radiat Oncol• Biol• Phys 93(3):S1CrossRefGoogle Scholar
  15. 15.
    Morrall MC, Pitchford NJ, Waters EC, Ablett KL, Stocks H, Walker D, Grundy RG (2014) Recommendations for assessing cognitive risks in young children treated for ependymoma for clinical and research protocols: evidence from a systematic literature review. J Pediatr Oncol 2(1):24–39CrossRefGoogle Scholar
  16. 16.
    Walsh KS, Noll RB, Annett RD, Patel SK, Patenaude AF, Embry L (2016) Standard of Care for Neuropsychological Monitoring in pediatric neuro-oncology: lessons from the Children’s Oncology Group (COG). Pediatr Blood Cancer 63(2):191–195CrossRefGoogle Scholar
  17. 17.
    Limond JA, Bull KS, Calaminus G, Kennedy CR, Spoudeas HA, Chevignard MP (2015) Quality of survival assessment in European childhood brain tumour trials, for children aged 5 years and over. Eur J Paediatr Neurol 19(2):202–210CrossRefGoogle Scholar
  18. 18.
    Aarsen FK, Paquier PF, Reddingius RE, Streng IC, Arts WF, Evera-Preesman M, Catsman-Berrevoets CE (2006) Functional outcome after low-grade astrocytoma treatment in childhood. Cancer 106(2):396–402CrossRefGoogle Scholar
  19. 19.
    Anderson V, Catroppa C, Morse S, Haritou F, Rosenfeld J (2005) Functional plasticity or vulnerability after early brain injury? Pediatrics 116(6):1374–1382CrossRefGoogle Scholar
  20. 20.
    Mann CJ (2003 Jan 1) Observational research methods. Research design II: cohort, cross sectional, and case-control studies. Emerg Med J 20(1):54–60CrossRefGoogle Scholar
  21. 21.
    Van der Plas E, Nieman BJ, Butcher DT, Hitzler JK, Weksberg R, Ito S, Schachar R (2015) Neurocognitive late effects of chemotherapy in survivors of acute lymphoblastic leukemia: focus on methotrexate. J Can Acad Child Adolesc Psychiatry 24(1):25Google Scholar
  22. 22.
    Bull KS, Spoudeas HA, Yadegarfar G, Kennedy CR (2007) Reduction of health status 7 years after addition of chemotherapy to craniospinal irradiation for medulloblastoma: a follow-up study in PNET 3 trial survivors—on behalf of the CCLG (formerly UKCCSG). J Clin Oncol 25(27):4239–4245CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Matthew C. H. J. Morrall
    • 1
    • 2
    Email author
  • Rosa Reed-Berendt
    • 1
  • Kate Moss
    • 1
  • Helen Stocks
    • 1
  • Alexandra L. Houston
    • 1
  • Poppy Siddell
    • 1
  • Susan Picton
    • 3
  • Richard Grundy
    • 4
  1. 1.Paediatric NeuropsychologyThe Leeds Teaching Hospitals NHS TrustLeedsUK
  2. 2.Consultant Paediatric Neuropsychologist, Paediatric NeuropsychologyLeedsUK
  3. 3.Paediatric OncologyThe Leeds Teaching Hospitals NHS TrustLeedsUK
  4. 4.Children’s Brain Tumour Research Centre, Academic Division of Child Health, Queen’s Medical CentreUniversity of NottinghamNottinghamUK

Personalised recommendations