Leptomeningeal metastasis

Leptomeningeal metastasis (LM) results from dissemination of cancer cells to both the leptomeninges (pia and arachnoid) and cerebrospinal fluid (CSF) compartment. Breast cancer, lung cancer, and melanoma are the most common solid tumors that cause LM. Recent approval of more active anticancer therapies has resulted in improvement in survival that is partly responsible for an increased incidence of LM. Neurologic deficits, once manifest, are mostly irreversible, and often have a significant impact on patient quality of life. LM-directed therapy is based on symptom palliation, circumscribed use of neurosurgery, limited field radiotherapy, intra-CSF and systemic therapies. Novel methods of detecting LM include detection of CSF circulating tumor cells and tumor cell-free DNA. A recent international guideline for a standardization of response assessment in LM may improve cross-trial comparisons as well as within-trial evaluation of treatment. An increasing number of retrospective studies suggest that molecular-targeted therapy, such as EGFR and ALK inhibitors in lung cancer, trastuzumab in HER2+ breast cancer, and BRAF inhibitors in melanoma, may be effective as part of the multidisciplinary management of LM. Prospective randomized trials with standardized response assessment are needed to further validate these preliminary findings.