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. 2025 Sep;174(2):401-409.
doi: 10.1007/s11060-025-05070-5. Epub 2025 May 16.

Long-term neurocognitive sequelae in pediatric medulloblastoma survivors treated according to the HIT protocol

Iuliia A Aldeeva  1 , Elena V Glebova  2   3 , Roza A Sarkisyan  2 , Elizaveta N Romanova  2 , Nadezhda M Karpova  2 , Valeriia G Shapovalova  2 , Alexander F Karelin  3
Affiliations

Long-term neurocognitive sequelae in pediatric medulloblastoma survivors treated according to the HIT protocol

Iuliia A Aldeeva et al. J Neurooncol. 2025 Sep.

Abstract

Objective: Medulloblastoma is the most prevalent malignant brain tumour in children. Although contemporary comprehensive anticancer therapy has been shown to result in favourable survival and relapse outcomes, the long-term toxic effects on cognitive and motor function remain a concern. This study aims to investigate the long-term neurotoxic effects on cognitive function in paediatric medulloblastoma survivors.

Method: Data from 70 patients (Mage = 12.7 ± 2.94 years, 40% female) in remission treated according to the HIT protocol who underwent comprehensive neuropsychological assessment were analyzed. General linear models (GLMs) were constructed to assess the contribution of remission duration, chemotherapy type, and radiation dose to variability in cognitive performance on the CANTAB and DTKI tests.

Results: GLM revealed that remission > 4 years was associated with poorer processing speed, attention, and executive functions: cognitive flexibility, inhibitory control, planning, and working memory compared to participants with shorter remission. Induction therapy with methotrexate had more pronounced long-term negative effects on processing speed. However, no significant effects were observed across different radiation doses.

Conclusions: Remission duration emerged as a more significant predictor of a poor neurocognitive outcome than chemotherapy type or radiation dose, that is, the longer the remission, the more pronounced the neurocognitive impairment becomes. This highlights the need for continued monitoring and the development of targeted rehabilitation interventions for paediatric medulloblastoma survivors.

Keywords: HIT; Long-term effects; Medulloblastoma; Neurotoxicity; Pediatric brain tumour survivors.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (protocol number 8/2017 of 24.10.2017). Information about the trial was provided to participants and their parents/legal representatives. Written informed consent was obtained from all participants or their parents/legal representatives. Précis: This study suggests that pediatric medulloblastoma patients treated with the HIT protocol experience cognitive decline that worsens after the completion of active treatment. Longer duration of remission is associated with poorer scores on cognitive tests which underscores the importance of continuous monitoring and targeted rehabilitative interventions for medulloblastoma survivors. Competing interests: The authors declare no competing interests.

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