Treatment of Leptomeningeal Spread of NSCLC: A Continuing Challenge

Leptomeningeal metastasis is a serious and frequently fatal complication of non-small cell lung cancer. Curative treatment remains elusive, but careful use of radiation, systemic chemotherapy, intrathecal chemotherapy, and symptoms management can greatly improve quality of life and survival. For most patients, we recommend a combination of skull-based radiation with focal radiation to any symptomatic spinal segments followed by systemic chemotherapy. For patients with EGFR mutations, erlotinib may be used as first-line therapy in a daily or high-dose regimen. Pemetrexed has promise for use in patients with brain and leptomeningeal metastases. Patients with multiple comorbidities or low performance status may tolerate intrathecal therapy better than systemic chemotherapy. The most commonly used intrathecal chemotherapies are methotrexate and liposomal cytarabine, although newer agents, such as topotecan and mafosfamide, may be more effective. Elevated intracranial pressure, which causes headaches, vertigo, nausea, and vomiting, should be treated with dexamethasone and acetazolamide. In select patients, cerebrospinal fluid shunting may be considered. The use of antidepressants, central nervous system stimulants, benzodiazepines, antiemetics, and pain medications can increase quality of life in patients with leptomeningeal metastases.