Leptomeningeal metastases, also known as carcinomatous meningitis, refers to the spread of malignant cells through the CSF space. These cells can originate from primary CNS tumors (e.g. drop metastases), as well as from distant tumors that have metastasized via hematogenous spread. Leptomeningeal metastases (LM) result from metastatic infiltration of the leptomeninges by malignant cells originating from an extrameningeal primary tumor site that may be extraneural (most common) or intraneural (less common).
Symptoms of LM result from cancer cells clogging the normal exits for CSF causing a fluid buildup and increased pressure in thebrain. This increased pressure can cause vague but uncomfortable symptoms including headaches (often worse in the morning), nausea, vision changes, and difficulty walking. Cancer cells can also disturb nerves exiting the brain causing numbness, weakness, or pain.
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The diagnosis of LM may be ascertained according to the National Comprehensive Cancer Network (NCCN) guidelines. The guidelines suggest any one of the following diagnostic criteria are sufficient to diagnose LM; CSF positive for tumor cells (positive CSF cytology); radiologic findings in the CNS consistent with LM irrespective of supportive clinical findings or alternatively and more controversial, clinical signs and symptoms consistent with LM and a nonspecific but abnormal CSF analysis (high white blood cell count, low glucose, and elevated protein) in a patient known to have a cancer.
The goal of treatment is to prolong survival and to maintain quality of the life by delaying further neurological deterioration. Therapeutic strategies include intrathecal pharmacotherapy, systemic pharmacotherapy and radiotherapy. Intrathecal therapy is widely used for the treatment of leptomeningeal metastases. There is a rationale to use intrathecal treatment in patients with floating tumor cells in the CSF and for linear diffuse or ependymal spread enhancement.
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However, intrathecal therapy has only a limited penetration into solid tumor lesions and may be inefficient and even toxic in case of CSF flow obstructions. In the latter situation, radiotherapy can be used to restore CSF flow—successful restoration should be checked prior the use of an intrathecal treatment.
The Leptomeningeal Metastases market has three key players, that is, Y-mAbs Therapeutics (177Lu-DTPA-Omburtamab Radioimmunotherapy), Plus Therapeutics (Rhenium-186 NanoLiposome ), and AngioChem (ANG1005). Novel targeted agents increasingly are being studied in the treatment of LM and may prove promising in the future. New clinical trials of LM based on a tumor-specific histology are needed to establish the role of these new approaches. Equally important in the management of LM is establishing a common method of assessing response to LM-directed treatment that would improve new trial design and enable cross trial comparisons.
Leptomeningeal disease/carcinomatosis, also known as neoplastic meningitis or carcinomatous meningitis, occurs when tumor cells infiltrate the leptomeninges of the brain and spinal cord, as well as the cerebrospinal fluid. Leptomeningeal disease is present at the time of initial intracranial involvement in 2%-12% of cases but, based on prospective studies, can also develop later in the clinical course in 1%-37% of patients.
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LM is present in 1-5% of patients with solid tumors, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors. Small-cell lung cancers spread to the leptomeninges in 9-25% of cases; melanomas, in 23%; and breast cancers, in 5%. It is estimated that leptomeningeal metastases, for malignancies in general, comprise approximately 4–7% of central nervous system (CNS) metastases, and in breast cancer, represent between 5% and 20% of CNS metastases. In patients with breast cancer in whom their metastatic disease is confined to the leptomeninges without parenchymal brain involvement, the prevalence is up to 3.5%.
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