The nervous system is exquisitely sensitive to the potential adverse sequelae of CNS-directed therapy. For example, intrathecal therapy may be associated with acute, sub-acute or chronic toxicities including paralysis and leukoencephalopathy.105-106 Likewise, radiation therapy may be associated with significant adverse effects including neuroendocrine deficits, neuropsychological deficits, leukoencephalopathy, and second malignancies.107"114 In addition to the toxicities associated with each specific agent or modality of therapy, there are many other variables that may affect the incidence and toxicities associated with CNS-directed therapy. These include the age at the time of therapy, concomitantly administered systemic therapies (e.g. methotrexate), and cumulative dose of specific therapeutic agents.115
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