Skip to main content
Log in

Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

High-dose chemotherapy (HDC) strategies were developed in brain tumor protocols for young children to prevent neuropsychological (NP) impairments associated with radiotherapy. However, comprehensive NP evaluations of these children treated with such strategies remain limited. We examined the long-term neurocognitive outcomes of young children (<6 years) with medulloblastoma, treated similarly, with a HDC strategy “according to” the chemotherapy regimen of the protocol CCG 99703. This retrospective study included young children less than 6 years of age at diagnosis of medulloblastoma treated from 1998 to 2011 at 7 North American institutions. Twenty-four patients who had at least one NP assessment post-treatment are the focus of the current study. Of 24 patients in this review, 15 (63%) were male and the mean age at diagnosis was 29.4 months (SD = 13.5). Posterior fossa syndrome (PFs) was reported in five patients (21%). Nine (37.5%) received radiotherapy (5 focal, 4 craniospinal). On average, children were assessed 3.5 years (SD = 1.8) post-diagnosis, and full-scale intellectual quotient (FSIQ) scores ranged from 56 to 119 (\({\bar{\text{X}}}\)= 92; SD = 16.8). The majority of children (74%) had low-average to average NP functioning. Very young children treated with radiotherapy, who needed hearing support or with PFs had worse neurocognitive outcomes. Clinically significant deficits (<10th percentile) in at least one area of NP functioning were found in 25% of the children. NP data obtained from this sample of survivors of medulloblastoma in early childhood, all treated with sequential HDC and 1/3 with radiotherapy, describe NP functioning within average normal limits overall. However, almost 25% of children had significant deficits in specific domains.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ris MD, Noll RB (1994) Long-term neurobehavioral outcome in pediatric brain-tumor patients: review and methodological critique. J Clin Exp Neuropsychol 16:21–42

    Article  CAS  PubMed  Google Scholar 

  2. Grill J, Sainte-Rose C, Jouvet A et al (2005) Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6:573–580. doi:10.1016/S1470-2045(05)70252-7

    Article  CAS  PubMed  Google Scholar 

  3. Rutkowski S, Bode U, Deinlein F et al (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986. doi:10.1056/NEJMoa042176

    Article  CAS  PubMed  Google Scholar 

  4. Ashley DM, Merchant TE, Strother D et al (2012) Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: Children’s Oncology Group study P9934. J Clin Oncol 30:3181–3186. doi:10.1200/JCO.2010.34.4341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Walter AW, Mulhern RK, Gajjar A et al (1999) Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children’s Research Hospital. J Clin Oncol 17:3720–3728

    Article  CAS  PubMed  Google Scholar 

  6. Sands SA, Oberg JA, Gardner SL et al (2010) Neuropsychological functioning of children treated with intensive chemotherapy followed by myeloablative consolidation chemotherapy and autologous hematopoietic cell rescue for newly diagnosed CNS tumors: an analysis of the Head Start II survivors. Pediatr Blood Cancer 54:429–436. doi:10.1002/pbc.22318

    Article  PubMed  Google Scholar 

  7. Bergthold G, El Kababri M, Varlet P et al (2014) High-dose busulfan-thiotepa with autologous stem cell transplantation followed by posterior fossa irradiation in young children with classical or incompletely resected medulloblastoma. Pediatr Blood Cancer 61:907–912. doi:10.1002/pbc.24954

    Article  CAS  PubMed  Google Scholar 

  8. Cohen BH, Geyer JR, Miller DC et al (2015) Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the ccg-99703 phase i/ii study. A report from the Children’s Oncology Group. Pediatr Neurol 53:31–46. doi:10.1016/j.pediatrneurol.2015.03.019

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lafay-Cousin L, Smith A, Chi SN, Wells E et al (2016). Clinical, pathological, and molecular characterization of infant medulloblastomas treated with sequential high-dose chemotherapy. Pediatr Blood Cancer 63: 1527–1534.doi:10.1002/pbc.26042

    Article  CAS  PubMed  Google Scholar 

  10. Chang KW, Chinosornvatana N (2010) Practical grading system for evaluating cisplatin ototoxicity in children. J Clin Oncol 28:1788–1795. doi:10.1200/JCO.2009.24.4228

    Article  CAS  PubMed  Google Scholar 

  11. Sullivan GM, Feinn R (2012) Using effect size - or Why the P value is not enough. J Grad Med Educ 4:279–282. doi:10.4300/JGME-D-12-00156.1

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ferguson CJ (2009) An effect size primer: a guide for clinicians and researchers. Prof Psychol Res Pract 40:532–538. doi:10.1037/a0015808]

    Article  Google Scholar 

  13. Lezak MD (1984) Neuropsychological assessment in behavioral toxicology–developing techniques and interpretative issues. Scand J Work Environ Health 10(Suppl 1):25–29

    PubMed  Google Scholar 

  14. Fay TB, Yeates KO, Wade SL et al (2009) Predicting longitudinal patterns of functional deficits in children with traumatic brain injury. Neuropsychology 23:271–282. doi:10.1037/a0014936

    Article  PubMed  PubMed Central  Google Scholar 

  15. Beauchamp M (2015) Empirical derivation and validation of a clinical case definition for neuropsychological impairment in children and adolescents. J Int Neuropsychol Soc 21(8):596–609. doi:10.1017/S1355617715000636

    Article  PubMed  Google Scholar 

  16. Brooks B, Iverson G (2012) Improving accuracy when identifying cognitive impairment in pediatric neuropsychological assessments. Pediatric forensic neuropsychology. Oxford University Press, New York, pp 66–88

    Google Scholar 

  17. Law N, Smith M Lou, Greenberg M et al (2015) Executive function in paediatric medulloblastoma: The role of cerebrocerebellar connections. J Neuropsychol. doi:10.1111/jnp.12082

    PubMed  Google Scholar 

  18. Palmer SL, Glass JO, Li Y et al (2012) White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor. Neuro Oncol 14:1185–1193. doi:10.1093/neuonc/nos154

    Article  PubMed  PubMed Central  Google Scholar 

  19. Schreiber JE, Gurney JG, Palmer SL et al (2014) Examination of risk factors for intellectual and academic outcomes following treatment for pediatric medulloblastoma. Neuro Oncol 16:1129–1136. doi:10.1093/neuonc/nou006

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li Y, Womer RB, Silber JH (2004) Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer 40:2445–2451. doi:10.1016/j.ejca.2003.08.009

    Article  CAS  PubMed  Google Scholar 

  21. Knight KRG, Kraemer DF, Neuwelt EA (2005) Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 23:8588–8596. doi:10.1200/JCO.2004.00.5355

    Article  PubMed  Google Scholar 

  22. Blair JC (1985) The effects of mild sensorineural hearing loss on academic performance of young school-age children. Volta Rev 87:87–93

    Google Scholar 

  23. Wells EM, Walsh KS, Khademian ZP et al (2008) The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder. Dev Disabil Res Rev 14:221–228. doi:10.1002/ddrr.25

    Article  PubMed  Google Scholar 

  24. Robertson PL, Muraszko KM, Holmes EJ et al (2006) Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg 105:444–451. doi:10.3171/ped.2006.105.6.444

    PubMed  Google Scholar 

  25. Ris MD, Walsh K, Wallace D et al (2013) Intellectual and academic outcome following two chemotherapy regimens and radiotherapy for average-risk medulloblastoma: COG A9961. Pediatr Blood Cancer 60:1350–1357. doi:10.1002/pbc.24496

    Article  PubMed  Google Scholar 

  26. Knight SJ, Conklin HM, Palmer SL, et al (2014) Working memory abilities among children treated for medulloblastoma: parent report and child performance. J Pediatr Psychol 39 1–11. doi:10.1093/jpepsy/jsu009

    Article  Google Scholar 

  27. Palmer SL, Leigh L, Ellison SC et al (2014) Feasibility and efficacy of a computer-based intervention aimed at preventing reading decoding deficits among children undergoing active treatment for medulloblastoma: results of a randomized trial. J Pediatr Psychol 39:450–458. doi:10.1093/jpepsy/jst095

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lucie Lafay-Cousin.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fay-McClymont, T.B., Ploetz, D.M., Mabbott, D. et al. Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach. J Neurooncol 133, 119–128 (2017). https://doi.org/10.1007/s11060-017-2409-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2409-9

Keywords

Navigation