title: Management of leptomeningeal malignancy.
abstract: Leptomeningeal carcinomatosis is defined as malignant infiltration of the pia matter and arachnoid membrane. Leukaemias and lymphomas, lung, breast cancer and melanoma are the primary tumours commonly associated with leptomeningeal carcinomatosis. Diagnosis is based on compatible symptoms and signs, cytological evidence of malignancy in the cerebrospinal fluid, and neuroimaging studies. Treatment is largely palliative (median survival 2-4 months). Patients with lympomatous or leukaemic meningitis, chemosensitive tumours such as breast cancer, low tumour burden, minimal neurological deficits, good performance status and controllable systemic disease survive longer with occasional long-term responses. Available treatment options include focal radiation therapy to CNS sites of bulky, symptomatic or obstructive meningeal deposits, intrathecal cytotoxic therapy and systemic chemotherapy. No evidence of superiority of intrathecal treatment compared with best palliative care (including radiation therapy and systemic treatment) is available from clinical trials. Novel treatment approaches include intrathecal liposomal Ara-C, the development of new cytotoxic compounds, signal transduction inhibitors and monoclonal antibodies for intrathecal or systemic use. Until data from multi-centre randomised trials are available, rationalisation of therapy should be done by stratifying patients to prognostic groups. High-risk patients will only survive for a few weeks and are better managed with supportive measures, whereas low-risk patients justify vigorous cerebrospinal fluid-directed treatment combined with radiation therapy and systemic chemotherapy.
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Panepistimiou Avenue, 45110 Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000465:Algorithms; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D016080:Arachnoid Cysts / Q000188:drug therapy* / Q000209:etiology / Q000532:radiotherapy; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003561:Cytarabine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007938:Leukemia / Q000473:pathology; D008223:Lymphoma / Q000473:pathology; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D010166:Palliative Care; D016032:Randomized Controlled Trials as Topic; D013852:Thiotepa / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D003561:Cytarabine; D019772:Topotecan; D013852:Thiotepa; D008727:Methotrexate