Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment.

University of Wisconsin Paul P Carbone Comprehensive Cancer Center 600 Highland Ave Madison WI, 537192.
Current Cancer Therapy Reviews 11/2011; 7(4):319-327. DOI: 10.2174/157339411797642597
Source: PubMed

ABSTRACT As therapeutic options and supportive care for the treatment of neoplastic disease have improved, there has been an associated increase in the incidence of leptomeningeal disease. In this review, the clinical presentation, natural history, diagnostic evaluation, and treatment options for this often devastating sequela of solid tumors, lymphoma, and leukemia will be summarized. The therapeutic efficacy of ionizing radiation, systemic agents, and intrathecal drugs will be examined from the existing literature. Additionally the pathophysiology, which in part defines the therapeutic limitations in approaching this patient population, will be discussed in order to assist in individualized clinical decision making.

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    ABSTRACT: Leptomeningeal carcinomatosis occurs very rarely in patients with pancreatic cancer. Leptomeningeal carcinomatosis is characterized by multifocal seeding of the leptomeninges by malignant cells that originate from a solid tumor. To the best of our knowledge, brain metastasis from pancreatic cancer is extremely rare. Leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of cases of solid tumors. The clinical manifestation usually involves neurological symptoms, including dizziness, headache, vomiting, nausea, and hemiparesis, symptoms similar to those of meningitis or brain tumors. Diagnostic methods for leptomeningeal carcinomatosis include brain magnetic resonance imaging and cerebrospinal fluid examination. Here, we describe a case of leptomeningeal carcinomatosis in which the primary tumor was later determined to be pancreatic cancer. Brain magnetic resonance imaging findings showed mild enhancement of the leptomeninges, and cerebrospinal fluid cytology was negative at first. However, after repeated spinal taps, atypical cells were observed on cerebrospinal fluid analysis and levels of tumor markers such as carbohydrate antigen 19-9 in cerebrospinal fluid were elevated. Abdominal computed tomography, performed to determine the presence of extracerebral tumors, revealed pancreatic cancer. Pancreatic cancer was confirmed histopathologically on examination of an endoscopic ultrasound-guided fine needle aspiration specimen.
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    ABSTRACT: Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma.
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    ABSTRACT: Purpose To assess the results of the treatment of patients with breast cancer leptomeningeal metastasis (LM) and to compare the efficacy of methotrexate and liposomal cytarabine in patients treated intrathecally by lumbar puncture. Patients and methods In this prospective observational study 149 consecutive patients with breast cancer and LM treated between the years 1999 and 2011 were assessed. Multimodality treatment methods were used: systemic therapy in 77 patients, radiation therapy in 92 patients, intrathecal methotrexate in 81 patients and intrathecal liposomal cytarabine in 15 patients. Results Median survival of all patients was 4.2 months. Median survival of patients in whom systemic intravenous/oral treatment was used was 6 months and in those without systemic treatment was 2 months (p <0.001). Median survival of patients treated with intrathecal methotrexate was 4.2 months, those treated with intrathecal liposomal cytarabine was 4.6 months and without intrathecal treatment was 3.7 months (p=0.717). Median survival after whole-brain radiation therapy was 4.6 months and without irradiation was 3.2 months (p=0.028). Multivariate analysis revealed that Karnofsky Performance Status of >70, systemic intravenous/oral treatment and bones as a site of metastases were factors prolonging survival from LM. Conclusion Among treatment methods, only systemic therapy prolonged survival in patients with LM. Nor radiation therapy neither lumbar intrathecal therapy influenced survival in those patients however both methods alleviated signs and symptoms of LM. No difference in survival was observed in patients treated intrathecally with methotrexate and those treated with liposomal cytarabine. Treatment with both drugs was comparable.
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