Pathophysiology and treatment of leptomeningeal metastases in lung cancer.

Leptomeningeal metastases (LMs) cause neurological symptoms, including nausea, headache, radicular pain, gait disturbance, and cranial nerve palsies. Lung and breast cancer as well as melanoma are the most common primary tumors in patients with leptomeningeal metastasis. The incidence of LMs is increasing, and this may be due to the improved survival of patients following the development of novel therapies, which may be less effective within the central nervous system. Barrier mechanisms in central nervous system such as blood-brain barrier constitute the critical interfaces between the periphery and brain that actively restrict the entry of solutes and cells into the brain parenchyma and leptomeninges. However, cancer cells could metastasize into the meninges via the brain or choroid plexus, by crossing pial blood vessels, or through vascular channels which connect the bone marrow and meninges. Conventional treatments for LMs, such as chemotherapy, photon-based radiation therapy, and intrathecal chemotherapy, have limited efficacy. However, advances in the understanding of the pathophysiology of LMs and novel treatment modalities are shifting this paradigm. Recent advances in molecularly targeted therapies, antibody-drug conjugates therapies, immunotherapies, intrathecal therapies, proton craniospinal irradiation, and expected therapies such as dendritic and NK cell-engaging therapies may improve the outcomes of patients with LMs. This mini review briefly outlines the pathophysiology and current treatment options for LMs.