Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported. 1. Introduction Neoplastic meningitis is due to dissemination of malignant cells to the leptomeninges and the subarachnoid space. It occurs in 10–15% of haemolymphoproliferative malignancies and in 5–10% of solid cancers [1]. It more frequently represents late complication of long-standing neoplastic disease, but in 10–15% of patients may be the first-ever manifestation of otherwise occult cancer [1]. The pathways for tumor dissemination to the leptomeninges and subarachnoid space include haematogenous route, perineural blood/lymphatic vessels, and direct infiltration from contiguous sites (for instance, dural and/or bone metastases close to the brain and spinal cord/root surface). Not only extra-CNS tumors, but also tumors arising within the CNS (among which gliomas, ependymomas, medulloblastomas, and germinomas) display relapses and/or multifocal presentations with distant foci and a supposedly intra-CSF pathway of dissemination of neoplastic cells. Guidelines for effective treatment of neoplastic meningitis are lacking, due to the low levels of evidence, which is mostly present for haemolymphoproliferative disease. In meningeal dissemination from solid extra-CNS tumors, and more so in distant spread of primitive CNS tumors, there is a lack of uniform approach due to a number of factors: among these, the belief of