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

Autoři: Holger Ottensmeier aff001;  Paul G. Schlegel aff001;  Matthias Eyrich aff001;  Johannes E. Wolff aff003;  Björn-Ole Juhnke aff004;  Katja von Hoff aff004;  Stefanie Frahsek aff001;  Rene Schmidt aff005;  Andreas Faldum aff005;  Gudrun Fleischhack aff006;  Andre von Bueren aff007;  Carsten Friedrich aff008;  Anika Resch aff008;  Monika Warmuth-Metz aff009;  Jürgen Krauss aff010;  Rolf D. Kortmann aff011;  Udo Bode aff012;  Joachim Kühl aff001;  Stefan Rutkowski aff004
Působiště autorů: Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany aff001;  Comprehensive Cancer Center Mainfranken, University Medical Center, Wuerzburg, Germany aff002;  AbbvVie, Oncology Development, Chicago, Illinois, United States of America aff003;  Department of Paediatric Haematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany aff004;  Institute of Biostatistics and Clinical Research, University Muenster, Muenster, Germany aff005;  Pediatrics III Oncology, University Hospital of Essen, Essen, Germany aff006;  Department of Paediatrics and Adolescent Medicine Division of Paediatric Haematology and Oncology, University Hospital of Geneva, Geneva, Switzerland aff007;  Department of Haematology Oncology, University Children´s Hospital Rostock, Rostock, Germany aff008;  Department of Neuroradiology, HIT 2000 National Reference Center, University Medical Center Wuerzburg, Wuerzburg, Germany aff009;  Department of Paediatric Neurosurgery, University of Wuerzburg, University Medical Center Wuerzburg, Wuerzburg, Germany aff010;  Department of Radiotherapy, University of Leipzig, Leipzig, Germany aff011;  Department of Paediatric Oncology, University of Bonn, Bonn, Germany aff012
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227693


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.

Klíčová slova:

Cancer chemotherapy – Cancer treatment – Cognition – Intelligence tests – Medulloblastoma – Neuropsychological testing – Neuropsychology – Surgical and invasive medical procedures


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