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Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol

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Abstract

Background

The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact.

Methods

A retrospective, multicenter study was conducted in 35 children under 5 years old, with a median follow-up of 72 months (range 14 to 130). The main analysis was performed in 30 patients who received cumulative doses of MTX as per-protocol (group 1). Five patients who received higher cumulative doses of MTX were analyzed separately. All follow-up MRIs and NP assessments were centrally reviewed by experts.

Results

Twenty patients in group 1 developed LE, grade 2 and 3 abnormalities did not correlate with higher cumulative doses of ITV-MTX (p = 0.698). Considering the most recent NP evaluation, the Full-Scale IQ (FSIQ) and Wechsler indices were in the average to lower average range. The FSIQ was deficient in 6/17 evaluable patients. Cumulative dose of ITV-MTX was almost associated with decreased processing speed competence (p = 0.055) which was the most frequently impaired neurocognitive domain. Neuropsychological assessment scores were not statistically lower in patients with persistent grade 2 LE at the end of follow-up.

Conclusion

This study described that the use of cumulative dose of MTX (IV and ITV) according to the HIT-SKK protocol resulted in LE that tented to decrease over time, without significant correlation with a decline in neuro-intellectual skills.

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Author information

Authors and Affiliations

  1. Department of Pediatric Onco-Hematology, University Hospital, Vandoeuvre-les-Nancy, 54500, France

    Marie-Sophie Merlin, Malika Mezloy-Destracque & Pascal Chastagner

  2. Department of Neuroradiology, University Hospital, Nancy, France

    Emmanuelle Schmitt

  3. Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France

    Christelle Dufour

  4. Department of Neurosurgery, University Hospital, Rennes, France

    Laurent Riffaud

  5. Department of Pediatric Onco-Hematology, University Hospital, Rennes, France

    Chloé Puiseux

  6. Department of Pediatric Onco-Hematology, University Hospital, Angers, France

    Emilie De Carli

  7. Department of Pediatric Onco-Hematology, University Hospital, Caen, France

    Damien Bodet

  8. Department of Pediatric Onco-Hematology, University Hospital, Bordeaux, France

    Céline Icher

  9. SIREDO Cancer Center (Care, Innovation and Research in Pediatric, Adolescents, and Young Adults Oncology), Curie Institute Paris, and University Paris Cité, Paris, France

    François Doz

  10. Pediatric Hemato-oncology Institute (IHOP), Centre Leon Bérard, Lyon, France

    Cécile Faure-Conter

  11. Department of Pediatric Onco-Hematology, University Hospital, Grenoble, France

    Anne Pagnier

  12. Department of Pediatric Onco-Hematology, University Hospital, Reims, France

    Claire Pluchart

  13. Department of Pediatric Onco-Hematology, University Hospital, Saint-Etienne, France

    Sandrine Thouvenin-Doulet

  14. Department of Pediatric Onco-Hematology, University Hospital of Tours, Tours, France

    Julien Lejeune

  15. Medical Assessment Unit, Data management and Statistics Unit, University Hospital of Nancy, Methodology, France

    Phi-Linh Nguyen Thi

Authors
  1. Marie-Sophie Merlin
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  4. Christelle Dufour
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  11. Cécile Faure-Conter
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  17. Pascal Chastagner
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Contributions

C Dufour, L Riffaud, C Puiseux, E De Carli, D Bodet, C Icher, F Doz, C Faure-Conter, A Pagnier, C Pluchart; S Thouvenin-Doulet and J Lejeune provided all patient data relevant to the writing of the manuscript. MS Merlin collected clinical, pathological and therapeutic data about included patients and wrote the main manuscript text and prepared Figures and Tables. E Schmitt performed a centralized review of all follow-up MRIs. MS Merlin and M Mezloy-Destracque performed an analysis of all neuropsychological assessment. P-L Ngyuen Thi carried out the statistical analysis. P Chastagner coordinated and supervised the entire research project.The main author declares that there is no conflict of interest. All authors reviewed the manuscript.

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Correspondence to Marie-Sophie Merlin.

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Merlin, MS., Schmitt, E., Mezloy-Destracque, M. et al. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol. J Neurooncol 163, 195–205 (2023). https://doi.org/10.1007/s11060-023-04328-0

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