Treatment of Meningeal Malignancy

Meningeal metastasis from cancer has become an increasingly frequent problem as the treatment of systemic disease improves. Leukemia, lymphoma and solid tumors may all metastasize to the meninges, where the blood-brain barrier may provide a sanctuary from cytotoxic concentrations of chemotherapeutic agents. Because meningeal disease may be clinically silent or may present with unusual signs and symptoms, it is important to maintain a high index of suspicion for this problem. Diagnosis is usually made by cerebrospinal fluid cytologic testing, magnetic resonance imaging, or both. Treatment options include radiation therapy, systemic chemotherapy and intrathecal chemotherapy. Systemic therapy usually requires administration of either very high drug doses or prolonged infusions in order to overcome the poor penetration of most anticancer agents into the central nervous system. Thus, systemic toxicity is often a major drawback to this approach. Intrathecal chemotherapy results in delivery of anticancer agents directly into the cerebrospinal fluid, usually with minimal systemic toxicity. Intrathecal chemotherapy may be administered by lumbar puncture or by use of an Ommaya reservoir with the tip in the ventricle. Studies are under way to evaluate new agents for both systemic and intrathecal administration. Further research is required to overcome this difficult clinical challenge.