title: Therapy of leptomeningeal metastasis in solid tumors.
abstract: Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Mack
authors.affiliation: Department of Radiation Oncology, MediClin Robert Janker Clinic & University of Bonn Medical Center, Bonn, Germany; Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Clinic & University of Bonn Medical Center, Bonn, Germany.
authors.forename: B G
authors.initials: BG
authors.lastname: Baumert
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany; Division of Experimental and Translational Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schäfer
authors.affiliation: Department of Radiology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Hattingen
authors.affiliation: Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Scheffler
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Herrlinger
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany; Division of Experimental and Translational Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany; Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Clinic & University of Bonn Medical Center, Bonn, Germany. Electronic address: martin.glas@ukb.uni-bonn.de.
authors.forename: M
authors.initials: M
authors.lastname: Glas
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use*; D006801:Humans; D007278:Injections, Spinal; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology / Q000556:secondary / Q000628:therapy; D008727:Methotrexate / Q000627:therapeutic use*; D009366:Neoplasm Seeding; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000379:methods; D013852:Thiotepa / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D013852:Thiotepa; D008727:Methotrexate
keywords: Intrathecal chemotherapy; Leptomeningeal carcinomatosis; Leptomeningeal metastasis; WBRT