Advances in the Diagnosis and Treatment of Leptomeningeal Disease

Leptomeningeal disease (LMD) is a rare, late complication of systemic cancer and is associated with significant neurological morbidity and high mortality. Here we provide an overview of this condition, summarizing key recent research findings and clinical practice trends in its diagnosis and treatment. We also review current clinical trials for LMD.Improved molecular diagnostic tools are in development to enable more sensitive detection of LMD, including circulating tumor cells and circulating tumor DNA. The use of targeted and CNS-penetrant therapeutics has shown survival improvements with tyrosine kinase inhibitors, antibody-drug conjugates, and select chemotherapy. However, these studies have primarily been phase I/II and retrospective analyses. There remains a dearth of clinical trials that include LMD patients. The combination of patient-specific molecular information and novel therapeutic approaches holds significant promise for improving outcomes in patients with LMD.