Leptomeningeal Disease and the Role of Intrathecal Therapy

Abstract

Leptomeningeal metastasis has been on the rise in liquid and solid malignancies and is often associated with a dismal prognosis. Multifocal neurologic signs and symptoms in patients with primary malignancies should prompt clinicians to assess for leptomeningeal metastasis. Diagnostic workup includes exam, neuroimaging, and CSF analysis along with newer diagnostic markers currently being validated and in early use. Treatment includes palliative radiation therapy and/or surgery, local or systemic chemotherapy for patients with good prognosis, and targeted therapy for those harboring identified genetic alterations. Repurposing of systemically used chemotherapeutic agents intrathecally has proven successful with few agents. New treatments are currently in trial including immune therapy, radioisotope-conjugated antibodies and growth factor, and protein fusions-targeted therapy. Characterization of the molecular phenotype of LM cancer cells is currently underway, and more work is needed to address the quantification of LM disease burden in order to better assess risk and response to treatment.