Key result
High-dose intravenous chemotherapy in childhood sarcoma survivors was associated with long-term leukoencephalopathy in 27.2% of patients and significantly lower neurocognitive functioning.
Why the study?
Knowledge was limited regarding the prevalence and persistence of chemotherapy-induced leukoencephalopathy in childhood sarcoma patients.
Does high-dose intravenous chemotherapy cause long-term leukoencephalopathy and neurocognitive deficits in childhood sarcoma survivors compared to healthy controls?
Cross-Sectional (n=68)
Does high-dose intravenous chemotherapy cause long-term leukoencephalopathy and neurocognitive deficits in childhood sarcoma survivors compared to healthy controls?
High-dose intravenous chemotherapy in childhood sarcoma survivors is associated with long-term leukoencephalopathy and neurocognitive deficits, particularly affecting processing speed.
May warrant neurocognitive monitoring in sarcoma survivors; leaves open causality and need for prospective studies.
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.
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Sleurs et al. (2019) conducted a cross-sectional in Childhood sarcoma (n=68). High-dose intravenous chemotherapy vs. Healthy age-matched controls was evaluated on Long-term leukoencephalopathy. High-dose intravenous chemotherapy in childhood sarcoma survivors was associated with long-term leukoencephalopathy in 27.2% of patients and significantly lower neurocognitive functioning.
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