cancers Review Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches Alessia Pellerino 1,* , Priscilla K. Brastianos 2, Roberta Rudà 1,3 and Riccardo Soffietti 1 1 Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy;
[email protected] (R.R.); riccardo.soffi
[email protected] (R.S.) 2 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02115, USA;
[email protected] 3 Department of Neurology, Castelfranco Veneto and Brain Tumor Board Treviso Hospital, 31100 Treviso, Italy * Correspondence:
[email protected]; Tel.: +39-011-633-4904 Simple Summary: Leptomeningeal metastases are a devastating complication of solid tumors with poor survival, regardless of the type of treatments. The limited efficacy of targeted agents is due to the molecular divergence between leptomeningeal recurrences and primary site, as well as the presence of a heterogeneous blood-brain barrier and blood-tumor barrier that interfere with the penetration of drugs into the brain. The diagnosis of leptomeningeal metastases is achieved by neurological examination, and/or brain and spinal magnetic resonance, and/or a positive cerebrospinal fluid cytology. The presence of neoplastic cells in the cerebrospinal fluid examination is the gold-standard for the diagnosis of leptomeningeal metastases; however, novel techniques known as “liquid biopsy” aim to improve the sensitivity and specificity in detecting circulating neoplastic cells or DNA in the cerebrospinal fluid. Targeted therapies and immunotherapies have changed the natural history Citation: Pellerino, A.; Brastianos, of metastatic solid tumors, including lung, breast cancer, and melanoma. Targeting actionable P.K.; Rudà, R.; Soffietti, R.