Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa - Results of the HIT 2000 trial.

Infant ependymoma medulloblastoma neuropsychological late effects quality of survival

Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
05 Jun 2024
Historique:
received: 10 12 2023
medline: 5 6 2024
pubmed: 5 6 2024
entrez: 5 6 2024
Statut: aheadofprint

Résumé

Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor. Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed. Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis. Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities.

Sections du résumé

BACKGROUND BACKGROUND
Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor.
METHODS METHODS
Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed.
RESULTS RESULTS
Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis.
CONCLUSION CONCLUSIONS
Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities.

Identifiants

pubmed: 38835160
pii: 7687860
doi: 10.1093/neuonc/noae092
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

Auteurs

Martin Mynarek (M)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Anne Rossius (A)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Anika Guiard (A)

Department of Pediatrics, University Hospital Rostock, Rostock, Germany.

Holger Ottensmeier (H)

Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Wuerzburg, Germany.

Katja von Hoff (K)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Department of Pediatric Hematology and Oncology, Charité - University Medicine, Berlin, Germany.

Denise Obrecht-Sturm (D)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Lisa Bußenius (L)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Carsten Friedrich (C)

Department for General Pediatrics and Pediatric Hematology and Oncology, University Children's Hospital Oldenburg, Oldenburg, Germany.

Andre O von Bueren (AO)

Division of Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, University Hospital of Geneva, Geneva, Switzerland.
CANSEARCH research platform in Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland.

Nicolas U Gerber (NU)

Department of Oncology, University Children's Hospital, Zurich, Switzerland.

Thomas Traunwieser (T)

Paediatrics and Adolescent Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.

Rolf-Dieter Kortmann (RD)

Department of Radiation Oncology, University of Leipzig, Leipzig, Germany.

Monika Warmuth-Metz (M)

Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany.

Brigitte Bison (B)

Department of Neuroradiology, University Hospital Augsburg, Augsburg, Germany.

Ulrich-W Thomale (UW)

Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Juergen Krauss (J)

Department for Neurosurgery, University Hospital Wuerzburg, Wuerzburg, Germany.

Torsten Pietsch (T)

Institute of Neuropathology, Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), University of Bonn, DZNE German Center for Neurodegenerative Diseases, Bonn, Germany.

Steven C Clifford (SC)

Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.

Stefan M Pfister (SM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.

Dominik Sturm (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.

Felix Sahm (F)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.

Tanja Tischler (T)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Stefan Rutkowski (S)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Classifications MeSH