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Leptomeningeal neoplasms
Authors:Jan Drappatz  Tracy T Batchelor
Institution:(1) Harvard Medical School, Department of Neurology, Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center, Center for Neuro-Oncology, 44 Binney Street SW 430, Boston, MA 02115, USA
Abstract:Opinion statement  Leptomeningeal metastasis is becoming an increasingly important late complication of cancer as survival from systemic disease increases, and due to the fact that many novel cancer drugs fail to achieve therapeutic concentrations in the central nervous system. It occurs when neoplastic cells enter cerebrospinal fluid (CSF) pathways, causing diffuse infiltration of the subarachnoid space of the brain and spinal cord. Definitive diagnosis is established by the demonstration of malignant cells in the CSF. However, in certain circumstances the presence of leptomeningeal enhancement on brain or spinal MRI may be sufficient to make the diagnosis. Early diagnosis and aggressive treatment may delay neurologic progression and can lead to prolonged survival and improvement of neurologic function in certain patients. The prognosis depends on the underlying malignancy but is often poor, with a median survival of 4 months, and most treatment interventions are palliative. Nevertheless, some patients respond to treatment, and some survive beyond 1 or 2 years after diagnosis. Areas of radiographic bulky disease or symptomatic tumor should receive radiotherapy. Intrathecal chemotherapy is most effective in patients with lymphoma, leukemia, or breast cancer and without evidence of bulky disease on neuroimaging. Intrathecal chemotherapy requires normal CSF flow, and the most commonly used agents are methotrexate, cytarabine, and thiotepa. In lieu of intrathecal therapy, systemic chemotherapy may occasionally be indicated in select patients in part based on its ability to penetrate into bulky disease. When hydrocephalus occurs, ventriculoperitoneal shunting frequently leads to rapid clinical improvement. There is hope that progress in diagnostic modalities and the development of more effective intrathecal antineoplastic drugs may decrease neurologic morbidity and improve quality of life and survival.
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