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.
Similar content being viewed by others
References
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
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
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
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
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
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
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
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
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
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
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
Ferguson CJ (2009) An effect size primer: a guide for clinicians and researchers. Prof Psychol Res Pract 40:532–538. doi:10.1037/a0015808]
Lezak MD (1984) Neuropsychological assessment in behavioral toxicology–developing techniques and interpretative issues. Scand J Work Environ Health 10(Suppl 1):25–29
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
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
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
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
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
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
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
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
Blair JC (1985) The effects of mild sensorineural hearing loss on academic performance of young school-age children. Volta Rev 87:87–93
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-017-2409-9