Toxicity of treatment for neoplastic meningitis

Neoplastic seeding of the leptomeninges often signifies limited life expectancy. Still, patients are frequently offered aggressive multimodality therapies to palliate symptoms, and, one hopes, to prolong survival. Treatment modalities directed at the central nervous system (CNS) include radiotherapy, intra-cerebrospinal fluid (CSF) chemotherapy, standard systemic chemotherapy, and systemic high-dose chemotherapy. Because many of these modalities are used in combination, it is often difficult to discern which mode is the predominant cause of either acute or delayed complications. This review summarizes the incidence, clinical manifestations, laboratory findings, and pathology related to acute and delayed toxicity of treatment. It describes complications associated with radiotherapy, the use of an intraventricular implanted device (ie, Ommaya device), adverse effects of intra-CSF chemotherapy, and neurotoxicity, either associated with high-dose chemotherapy or manifested as delayed and chronic complications of combined therapies. All CNS-directed therapies are associated with a high rate of complications. The adverse effects of therapy profoundly affect the patient's quality of life, both at the acute phase of treatment and in late and chronic complications after therapy is completed. Intra-CSF chemotherapy is associated with a high rate of acute, reversible adverse effects that sometimes evolve into life-threatening medical conditions. Devastating delayed complications, mainly described as leukoencephalopathy, develop in more than 50% of patients who survive for extended periods and often lead to progressive loss of cognitive capacities. Careful assessment of the benefits and potential adverse reactions to a particular therapy regimen is mandated.