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MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol

BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX)...

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Autores principales: Merlin, Marie-Sophie, Schmitt, Emmanuelle, Mezloy-Destracque, Malika, Dufour, Christelle, Riffaud, Laurent, Puiseux, Chloé, De Carli, Emilie, Bodet, Damien, Icher, Céline, Doz, François, Faure-Conter, Cécile, Pagnier, Anne, Pluchart, Claire, Thouvenin-Doulet, Sandrine, Lejeune, Julien, Thi-Lambert, Phi-Linh Nguyen, Chastagner, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164847/
http://dx.doi.org/10.1093/neuonc/noac079.388
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author Merlin, Marie-Sophie
Schmitt, Emmanuelle
Mezloy-Destracque, Malika
Dufour, Christelle
Riffaud, Laurent
Puiseux, Chloé
De Carli, Emilie
Bodet, Damien
Icher, Céline
Doz, François
Faure-Conter, Cécile
Pagnier, Anne
Pluchart, Claire
Thouvenin-Doulet, Sandrine
Lejeune, Julien
Thi-Lambert, Phi-Linh Nguyen
Chastagner, Pascal
author_facet Merlin, Marie-Sophie
Schmitt, Emmanuelle
Mezloy-Destracque, Malika
Dufour, Christelle
Riffaud, Laurent
Puiseux, Chloé
De Carli, Emilie
Bodet, Damien
Icher, Céline
Doz, François
Faure-Conter, Cécile
Pagnier, Anne
Pluchart, Claire
Thouvenin-Doulet, Sandrine
Lejeune, Julien
Thi-Lambert, Phi-Linh Nguyen
Chastagner, Pascal
author_sort Merlin, Marie-Sophie
collection PubMed
description BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders.
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spelling pubmed-91648472022-06-05 MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol Merlin, Marie-Sophie Schmitt, Emmanuelle Mezloy-Destracque, Malika Dufour, Christelle Riffaud, Laurent Puiseux, Chloé De Carli, Emilie Bodet, Damien Icher, Céline Doz, François Faure-Conter, Cécile Pagnier, Anne Pluchart, Claire Thouvenin-Doulet, Sandrine Lejeune, Julien Thi-Lambert, Phi-Linh Nguyen Chastagner, Pascal Neuro Oncol Medulloblastoma BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders. Oxford University Press 2022-06-03 /pmc/articles/PMC9164847/ http://dx.doi.org/10.1093/neuonc/noac079.388 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Medulloblastoma
Merlin, Marie-Sophie
Schmitt, Emmanuelle
Mezloy-Destracque, Malika
Dufour, Christelle
Riffaud, Laurent
Puiseux, Chloé
De Carli, Emilie
Bodet, Damien
Icher, Céline
Doz, François
Faure-Conter, Cécile
Pagnier, Anne
Pluchart, Claire
Thouvenin-Doulet, Sandrine
Lejeune, Julien
Thi-Lambert, Phi-Linh Nguyen
Chastagner, Pascal
MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title_full MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title_fullStr MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title_full_unstemmed MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title_short MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
title_sort medb-13. neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the hit-skk protocol
topic Medulloblastoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164847/
http://dx.doi.org/10.1093/neuonc/noac079.388
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