Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials: Neuropsychological outcome 5 years after treatment

PLoS One. 2020 Jan 23;15(1):e0227693. doi: 10.1371/journal.pone.0227693. eCollection 2020.

Abstract

Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005. Testing was performed using the validated Wuerzburg Intelligence Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor Integration, finger tapping "Speed", and the Continuous Performance Test. Of 104 patients in 47 centres, 72 were eligible for analyses. We assessed whether IQ was impacted by disease extent, disease location, patient age, gender, age at surgery, and treatment (chemotherapy with our without craniospinal irradiation [CSI] or local radiotherapy [LRT]). Median age at surgery was 2.3 years. Testing was performed at a median of 4.9 years after surgery. Patients with infratentorial EPs (treated with LRT) scored highest in fluid intelligence (CPM 100.9±16.9, mean±SD); second best scores were achieved by patients with MB without metastasis treated with chemotherapy alone (CPM 93.9±13.2), followed by patients with supratentorial EPs treated with LRT. In contrast, lowest scores were achieved by patients that received chemotherapy and CSI, which included children with metastasised MB and those with relapsed MB M0 (CPM 71.7±8.0 and 73.2±21.8, respectively). Fine motor skills were reduced in all groups. Multivariable analysis revealed that type of treatment had an impact on IQ, but essentially not age at surgery, time since surgery or gender. Our results confirm previous reports on the detrimental effects of CSI in a larger cohort of children. Comparable IQ scores in children with MB treated only with chemotherapy and in children with EP suggest that this treatment strategy represents an attractive option for children who have a high chance to avoid application of CSI. Longitudinal follow-up examinations are warranted to assess long-term neuropsychological outcomes.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Combined Modality Therapy
  • Craniospinal Irradiation / adverse effects
  • Cross-Sectional Studies
  • Ependymoma / pathology
  • Ependymoma / physiopathology
  • Ependymoma / therapy*
  • Female
  • Follow-Up Studies
  • Germany
  • Humans
  • Infant
  • Intelligence
  • Male
  • Medulloblastoma / physiopathology
  • Medulloblastoma / psychology
  • Medulloblastoma / therapy*
  • Motor Skills
  • Multivariate Analysis
  • Neuropsychological Tests
  • Treatment Outcome

Grants and funding

The neuropsychological testing study was funded by the Deutsche Kinderkrebsstiftung (German Children’s Cancer Foundation, https://www.kinderkrebsstiftung.de/startseite.html). Grants were awarded to H.O., P.G.S., and S.R (#DKS 2007.07, #DKS 2009.15, #DKS 2010.09, and #DKS A2013/04). The HIT2000/HIT-MED and HIT-REZ-2005 clinical trials were also funded by the Deutsche Kinderkrebsstiftung since 2001 and 2005, respectively. Further support was received from the Elterninitiative Leukaemie- und tumorkranker Kinder Wuerzburg e.V (www.stationregenbogen.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.E.W. is currently a employee of AbbVie, but during the trial and data analysis he served as a clinical neurooncologist in several hospitals, lastly Cleveland Clinic, Ohio. AbbVie provides support in the form of salaries for author J.E.W., but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.