Leptomeningeal metastasis: survival and prognostic factors in 155 patients
Introduction
The dissemination of tumor cells within the subarachnoid space is a devastating complication of systemic cancer. Except for some hematological malignancies [1], [2], leptomeningeal metastasis (LM) is usually a feature of advanced stages of disease. Due to more effective systemic chemotherapy and therefore prolonged survival and due to more sensitive diagnostic tools such as magnetic resonance imaging (MRI), the frequency of antemortem-diagnosed LM may have increased during the last decades. Nevertheless, the knowledge about pathogenesis, rational therapy, and prognostic factors in LM has remained scarce. Only few larger retrospective case collections [3], [4], [5], [6], [7] and some prospective trials of intrathecal (i.t.) [8], [9], [10], [11], [12], [13], [14], [15] or systemic intravenous (i.v.) chemotherapy [16], [17] have been published.
The clinical presentation is characterized by symptoms and signs attributable to one or more levels of the nervous system, symptoms and signs of increased intracranial pressure, psychomotor slowing and seizures [2], [3], [7], [18].The treatment of patients with LM is almost always palliative. Therapy commonly consists of i.t. chemotherapy [methotrexate (MTX), AraC, thiotepa] with or without radiotherapy [4], [6], [7], [11], [12], [13]. Other authors advocate the application of systemic (i.v. or oral) chemotherapy rather than i.t. chemotherapy [16], [17], [19]. Randomized studies comparing i.t. and systemic chemotherapy for LM have not been performed. Therefore, given the current uncertainty about the best therapeutic approach to LM, we analyzed therapy-dependent and therapy-independent prognostic factors in the largest cohort of patients with LM reported to date.
Section snippets
Study population
This retrospective study includes 155 consecutive patients diagnosed with LM at the Department of Neurology, University of Tuebingen Medical School between September 1980 and April 2002. Some of these patients were included in previous reports on clinical [20] or cerebrospinal fluid (CSF) findings in LM [21], [22], [23] or primary CNS lymphoma (PCNSL) [24], [25], [26], [27]. All patient records were evaluated for type and status of the primary tumor and metastases, CSF findings and neuroimaging
Study population
From 1980 to 2002, 155 patients with LM were diagnosed and treated at the University of Tuebingen Medical School (69 male, 86 female, median age 53 years, range 16–87 years). The largest subgroup of patients had primary brain tumors, particularly glioblastoma. Other large subgroups comprised patients with breast cancer, melanoma, and lung cancer. Diagnostic work-up did not reveal any extra-CNS tumor deposits in nine patients, classified as cancer of unknown primary (CUP; Table 1). The median
Discussion
This large database on the diagnosis and clinical course of LM in 155 consecutive patients followed at a single institution resulted in the identification of three therapy-independent predictors of poor outcome, age >60, and elevated levels of CSF lactate and albumin. Moreover, it suggests a role in improving outcome for systemic chemotherapy specifically in LM patients with leptomeningeal lesions detected by neuroimaging.
The percentage of patients with primary brain tumors was relatively high
Acknowledgements
The authors thank Christoph Meisner, MA, Institute for Medical Information Processing, University of Tuebingen, for valuable help with statistical analysis.
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