Skip to main content
Top
Published in: Child's Nervous System 3/2019

01-03-2019 | ORIGINAL ARTICLE

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

Authors: Matthew C. H. J. Morrall, Rosa Reed-Berendt, Kate Moss, Helen Stocks, Alexandra L. Houston, Poppy Siddell, Susan Picton, Richard Grundy

Published in: Child's Nervous System | Issue 3/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference 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):247–257CrossRefPubMedPubMedCentral 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):247–257CrossRefPubMedPubMedCentral
3.
4.
go back to reference 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):837–843CrossRef 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):837–843CrossRef
5.
go back to reference 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):152–158CrossRef 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):152–158CrossRef
6.
go back to reference 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–e100 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–e100
7.
go back to reference 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):15050–15057 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):15050–15057
8.
go back to reference 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):1185–1193CrossRefPubMedPubMedCentral 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):1185–1193CrossRefPubMedPubMedCentral
9.
go back to reference UKCCSG (1993) Management of children aged less than 3 years with brain tumours: UKCCSG study CNS 9204 UKCCSG (1993) Management of children aged less than 3 years with brain tumours: UKCCSG study CNS 9204
10.
go back to reference 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):696–705CrossRefPubMed 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):696–705CrossRefPubMed
11.
go back to reference 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):807–814 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):807–814
12.
go back to reference 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):1288–1296CrossRefPubMed 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):1288–1296CrossRefPubMed
13.
go back to reference 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):3156–3162CrossRefPubMed 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):3156–3162CrossRefPubMed
14.
go back to reference 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):S1CrossRef 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):S1CrossRef
15.
go back to reference 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):24–39CrossRef 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):24–39CrossRef
16.
go back to reference 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):191–195CrossRefPubMed 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):191–195CrossRefPubMed
17.
go back to reference 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):202–210CrossRefPubMed 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):202–210CrossRefPubMed
18.
go back to reference 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):396–402CrossRefPubMed 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):396–402CrossRefPubMed
19.
go back to reference Anderson V, Catroppa C, Morse S, Haritou F, Rosenfeld J (2005) Functional plasticity or vulnerability after early brain injury? Pediatrics 116(6):1374–1382CrossRefPubMed Anderson V, Catroppa C, Morse S, Haritou F, Rosenfeld J (2005) Functional plasticity or vulnerability after early brain injury? Pediatrics 116(6):1374–1382CrossRefPubMed
20.
21.
go back to reference 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):25PubMedPubMedCentral 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):25PubMedPubMedCentral
22.
go back to reference 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):4239–4245CrossRefPubMed 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):4239–4245CrossRefPubMed
Metadata
Title
Neurocognitive, academic and functional outcomes in survivors of infant ependymoma (UKCCSG CNS 9204)
Authors
Matthew C. H. J. Morrall
Rosa Reed-Berendt
Kate Moss
Helen Stocks
Alexandra L. Houston
Poppy Siddell
Susan Picton
Richard Grundy
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 3/2019
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-018-4015-3

Other articles of this Issue 3/2019

Child's Nervous System 3/2019 Go to the issue