Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May;163(1):195-205.
doi: 10.1007/s11060-023-04328-0. Epub 2023 May 12.

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

Marie-Sophie Merlin  1 , Emmanuelle Schmitt  2 , Malika Mezloy-Destracque  3 , Christelle Dufour  4 , Laurent Riffaud  5 , Chloé Puiseux  6 , Emilie De Carli  7 , Damien Bodet  8 , Céline Icher  9 , François Doz  10 , Cécile Faure-Conter  11 , Anne Pagnier  12 , Claire Pluchart  13 , Sandrine Thouvenin-Doulet  14 , Julien Lejeune  15 , Phi-Linh Nguyen Thi  16 , Pascal Chastagner  3
Affiliations

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

Marie-Sophie Merlin et al. J Neurooncol. 2023 May.

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.

Keywords: Leukoencephalopathy; Medulloblastoma; Methotrexate; Neurocognitive disorders; Quality of life.

PubMed Disclaimer

References

    1. Lafay-Cousin L, Bouffet E, Hawkins C, Amid A, Huang A, Mabbott DJ (2009) Impact of radiation avoidance on survival and neurocognitive outcome in infant medulloblastoma. Curr Oncol Tor Ont Dec 16(6):21–28
    1. Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM et al (1999) Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the children’s Cancer Group 921 randomized phase III study. J Clin Oncol Off J Am Soc Clin Oncol Mar 17(3):832–845 - DOI
    1. Kellie SJ (1999) Chemotherapy of central nervous system tumours in infants. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg Oct 15(10):592–612 - DOI
    1. Merchant TE, Schreiber JE, Wu S, Lukose R, Xiong X, Gajjar A (2014) Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma. Int J Radiat Oncol Biol Phys 1 Nov 90(3):554–561 - DOI
    1. Mulhern RK, Kepner JL, Thomas PR, Armstrong FD, Friedman HS, Kun LE (1998) Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J Clin Oncol Off J Am Soc Clin Oncol May 16(5):1723–1728 - DOI

LinkOut - more resources