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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; 15(1):e0227693Plos

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.

Authors+Show Affiliations

Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany.Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany. Comprehensive Cancer Center Mainfranken, University Medical Center, Wuerzburg, Germany.Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany.AbbvVie, Oncology Development, Chicago, Illinois, United States of America.Department of Paediatric Haematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany.Department of Paediatric Haematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany.Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany.Institute of Biostatistics and Clinical Research, University Muenster, Muenster, Germany.Institute of Biostatistics and Clinical Research, University Muenster, Muenster, Germany.Pediatrics III Oncology, University Hospital of Essen, Essen, Germany.Department of Paediatrics and Adolescent Medicine Division of Paediatric Haematology and Oncology, University Hospital of Geneva, Geneva, Switzerland.Department of Haematology Oncology, University Children´s Hospital Rostock, Rostock, Germany.Department of Haematology Oncology, University Children´s Hospital Rostock, Rostock, Germany.Department of Neuroradiology, HIT 2000 National Reference Center, University Medical Center Wuerzburg, Wuerzburg, Germany.Department of Paediatric Neurosurgery, University of Wuerzburg, University Medical Center Wuerzburg, Wuerzburg, Germany.Department of Radiotherapy, University of Leipzig, Leipzig, Germany.Department of Paediatric Oncology, University of Bonn, Bonn, Germany.Department of Paediatric Haematology and Oncology, University Children's Hospital, University Medical Center, Wuerzburg, Germany.Department of Paediatric Haematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31971950

Citation

Ottensmeier, Holger, et al. "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, vol. 15, no. 1, 2020, pp. e0227693.
Ottensmeier H, Schlegel PG, Eyrich M, et al. 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;15(1):e0227693.
Ottensmeier, H., Schlegel, P. G., Eyrich, M., Wolff, J. E., Juhnke, B. O., von Hoff, K., ... Rutkowski, S. (2020). 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, 15(1), pp. e0227693. doi:10.1371/journal.pone.0227693.
Ottensmeier H, et al. 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;15(1):e0227693. PubMed PMID: 31971950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ottensmeier,Holger, AU - Schlegel,Paul G, AU - Eyrich,Matthias, AU - Wolff,Johannes E, AU - Juhnke,Björn-Ole, AU - von Hoff,Katja, AU - Frahsek,Stefanie, AU - Schmidt,Rene, AU - Faldum,Andreas, AU - Fleischhack,Gudrun, AU - von Bueren,Andre, AU - Friedrich,Carsten, AU - Resch,Anika, AU - Warmuth-Metz,Monika, AU - Krauss,Jürgen, AU - Kortmann,Rolf D, AU - Bode,Udo, AU - Kühl,Joachim, AU - Rutkowski,Stefan, Y1 - 2020/01/23/ PY - 2019/04/02/received PY - 2019/12/24/accepted PY - 2020/1/24/entrez PY - 2020/1/24/pubmed PY - 2020/1/24/medline SP - e0227693 EP - e0227693 JF - PloS one JO - PLoS ONE VL - 15 IS - 1 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31971950/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 L2 - http://dx.plos.org/10.1371/journal.pone.0227693 DB - PRIME DP - Unbound Medicine ER -