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Long‐term leukoencephalopathy and neurocognitive functioning in childhood sarcoma patients treated with high‐dose intravenous chemotherapy
Author(s) -
Sleurs Charlotte,
Lemiere Jurgen,
Radwan Ahmed,
Verly Marjolein,
Elens Iris,
Renard Marleen,
Jacobs Sandra,
Sunaert Stefan,
Deprez Sabine,
Uyttebroeck Anne
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27893
Subject(s) - leukoencephalopathy , medicine , neurocognitive , methotrexate , chemotherapy , magnetic resonance imaging , working memory , oncology , sarcoma , white matter , pediatrics , pathology , radiology , psychiatry , cognition
Purpose Knowledge is limited regarding the prevalence and persistence of chemotherapy‐induced leukoencephalopathy in childhood sarcoma patients. This study explored the presence, clinical relevance, and potential risk factors of leukoencephalopathy in childhood bone and soft tissue sarcoma survivors, treated with intravenous chemotherapy. Methods We acquired cross‐sectional neurocognitive data in adult survivors ( n = 34) (median age at diagnosis [AaD] = 13.32 years, age range = 16‐35 years) and healthy age‐matched controls ( n = 34). Additionally, magnetic resonance imaging included T2‐weighted FLAIR (leukoencephalopathy Fazekas rating), multiexponential T2 relaxation (MET2), and multishell diffusion MRI to estimate myelin integrity‐related metrics and fluid movement restrictions. Finally, chemotherapy subgroups (methotrexate, alkylating agents, or combination), AaD, and Apoε and MTHFRC677T polymorphisms were explored as potential risk factors for leukoencephalopathy. Results At the group level, quality of life, working memory, processing speed, and visual memory were significantly lower in patients compared to controls. Furthermore, long‐term leukoencephalopathy was observed in 27.2% of the childhood sarcoma survivors, which was related to attentional processing speed. Lesions were related to diffusion‐derived, but not to myelin‐sensitive metrics. A significant interaction effect between AaD and chemotherapy group demonstrated more lesions in case of high‐dose methotrexate (HD‐MTX) ( F = 3.434, P = .047). However, patients treated with alkylating agents (without HD‐MTX) also showed lesions in younger patients. Genetic predictors were nonsignificant. Conclusion and implication This study suggests long‐term leukoencephalopathy with possibly underlying changes in vasculature, inflammation, or axonal injury, but not necessarily long‐term demyelination. Such lesions could affect processing speed, and as such long‐term daily life functioning of these patients.