Advances in the diagnosis, evaluation, and management of leptomeningeal disease

Abstract

Leptomeningeal metastasis (LM) is a devastating complication of cancer with variable clinical presentation and limited benefit from existing treatment options. In this review, we discuss advances in LM diagnostics and therapeutics with the potential to reverse this grim course. Emerging cerebrospinal fluid circulating tumor cell and cell-free tumor DNA analysis technologies will improve diagnosis of LM, while providing crucial genetic information, capturing tumor heterogeneity, and quantifying disease burden. Circulating tumor cells and cell-free tumor DNA have utility as biomarkers to track disease progression and treatment response. Treatment options for LM include ventriculoperitoneal shunting for symptomatic relief, radiation therapy including whole-brain radiation and focal radiation for bulky leptomeningeal involvement, and systemic and intrathecal medical therapies, including targeted and immunotherapies based on tumor mutational profiling. While existing treatments for LM have limited efficacy, recent advances in liquid biopsy together with increasing availability of targeted treatments will lead to rational multimodal individualized treatments and improved patient outcomes.

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

“…For example, contamination of the CSF sample with peripheral blood lymphocytes from an active systemic lymphoma patient could give a false-positive cytology [ 76 ]. Additionally, the high number of mitotic B cells (CSF pleocytosis) noticed in patients with multiple sclerosis or other immune-related inflammatory diseases could also give a false-positive cytology [ 77 , 78 , 79 , 80 ].…”

Solitary Leptomeningeal Metastasis from Lung Cancer: A Case Report

“…15) While recent advances in liquid biopsy technologies that detect circulating tumor cells and cell-free tumor DNA in the CSF have the potential to improve LM diagnosis, they have not yet been adopted into diagnostic guide-NMC Case Report Journal Vol. 9, 2022 3,[16][17][18][19][20][21] In the present case, by performing tumor resection instead of CSF cytology, we promptly and accurately diagnosed LM.…”

“…CSF cytology is another gold standard for LM diagnosis 4,6) and is based on the presence of malignant cells in the CSF or leptomeningeal biopsy. 3,6) However, the sensitivity of CSF analysis is reported to be low. 15) Increased opening pressure, lymphocytic pleocytosis, elevated protein, and decreased glucose are the most frequent observations in the CSF of LM patients, but they are not specific to LM.…”

“…6) The results of CSF cytology may be inconclusive because non-definitive, atypical, or suspicious cells can be isolated. 3) Thus, multiple cytological CSF examinations are often needed to confirm LM diagnosis because the sensitivity increases to 80%-90% after the second or third lumbar puncture. 15) While recent advances in liquid biopsy technologies that detect circulating tumor cells and cell-free tumor DNA in the CSF have the potential to improve LM diagnosis, they have not yet been adopted into diagnostic guide-NMC Case Report Journal Vol.…”

“…2) While central nervous system metastases mainly occur in the brain parenchyma, metastatic cancer cells can also spread to the pia mater and arachnoid membrane, which is referred to as leptomeningeal metastases (LM). 3) LM affects approximately 4%-15% of patients with solid cancers, and LM patients have a poor prognosis, with a mean survival time of 2-6 months, even with treatment. 4,5) Considering its devastating impact on the quality of life, a prompt and accurate diagnosis of LM is crucial.…”