Leptomeningeal metastasis from solid tumors

Thakkar, Jigisha P.; Kumthekar, Priya; Dixit, Karan; Stupp, Roger; Lukas, Rimas V.

doi:10.1016/j.jns.2020.116706

Cited by 49 publications

(34 citation statements)

References 117 publications

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“…Once LMC is suspected, it is important to confirm the diagnosis as early as possible. The initial evaluation is usually with gadolinium-enhanced brain and spine MRI and CSF studies [11]. MRI will typically show enhancement of the leptomeninges following the lines of the sulci, either focally or diffusely.…”

Section: Discussionmentioning

confidence: 99%

Leptomeningeal Carcinomatosis Secondary to a Gastrointestinal Stromal Tumor

Wlock

Patel

et al. 2021

Cureus

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A 66-year-old male presented to the emergency department (ED) with altered mental status and concern for stroke. Seven months prior to presentation, the patient was diagnosed with a benign gastrointestinal stromal tumor (GIST), for which he did not receive further workup. Initially, there was a concern for a stroke, however, CT of the brain, CT angiography of the head and neck, and MRI of the brain were negative for any acute abnormalities. Lumbar puncture (LP) revealed a low glucose level with increased protein and white blood cells in the cerebrospinal fluid (CSF). The patient did not display the typical signs and symptoms of meningitis, however, inpatient antibiotic treatment was initiated. The patient continued to deteriorate and repeat LP with cytology was ordered, which revealed malignant cells that were similar to the biopsy of the GIST; our patient was diagnosed with leptomeningeal carcinomatosis (LMC) secondary to the GIST. This case report presents a rare complication of a solid GIST and highlights the need for a high clinical index of suspicion for LMC, including those previously deemed to be benign.

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Section: Discussionmentioning

confidence: 99%

Leptomeningeal Carcinomatosis Secondary to a Gastrointestinal Stromal Tumor

Wlock

Patel

et al. 2021

Cureus

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“…Intrathecally-administered agents (whether given by the lumbar or ventricular route) are only expected to permeate tissue to a depth of a few millimeters, and therefore could only rationally be used in LM patients with non-bulky disease (1,42,43). Use of Etop-MNPs would improve upon this situation because they could be used to focally increase drug delivery, even to areas that represent "blind alleys" with respect to CSF access (16).…”

Section: Discussionmentioning

confidence: 99%

“…Seeding of malignant cells into cerebrospinal fluid (CSF) is a cause of severe morbidity and death in patients with metastatic non-CNS tumors (especially lung cancer), as well as those with primary CNS tumors, notably medulloblastoma (1)(2)(3)(4). Medulloblastoma cells are notorious for CSF pathway dissemination, which is found in 30-40% of children at initial diagnosis and the majority at recurrence (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…Medulloblastoma cells are notorious for CSF pathway dissemination, which is found in 30-40% of children at initial diagnosis and the majority at recurrence (5)(6)(7). Intrathecal chemotherapy, such as with etoposide or methotrexate, has been attempted for patients having disseminated medulloblastoma, and leptomeningeal metastases (LM) from solid tumors (1,2,5,(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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Etoposide-Bound Magnetic Nanoparticles Designed for Remote Targeting of Cancer Cells Disseminated Within Cerebrospinal Fluid Pathways

et al. 2020

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Magnetic nanoparticles (MNPs) have potential for enhancing drug delivery in selected cancer patients, including those which have cells that have disseminated within cerebrospinal fluid (CSF) pathways. Here, we present data related to the creation and in vitro use of new two-part MNPs consisting of magnetic gold-iron alloy cores which have streptavidin binding sites, and are coated with biotinylated etoposide. Etoposide was chosen due to its previous use in the CSF and ease of biotinylation. Etoposide magnetic nanoparticles (“Etop-MNPs”) were characterized by several different methods, and moved at a distance by surface-walking of MNP clusters, which occurs in response to a rotating permanent magnet. Human cell lines including D283 (medulloblastoma), U138 (glioblastoma), and H2122 (lung adenocarcinoma) were treated with direct application of Etop-MNPs (and control particles), and after remote particle movement. Cell viability was determined by MTT assay and trypan blue exclusion. Results indicated that the biotinylated etoposide was successfully bound to the base MNPs, with the hybrid particle attaining a maximum velocity of 0.13 ± 0.018 cm/sec. Etop-MNPs killed cancer cells in a dose-dependent fashion, with 50 ± 6.8% cell killing of D283 cells (for example) with 24 h of treatment after remote targeting. U138 and H2122 cells were found to be even more susceptible to the killing effect of Etop-MNPs than D283 cells. These findings indicate that the novel Etop-MNPs have a cytotoxic effect, and can be moved relatively rapidly at physiologic distances, using a rotating magnet. While further testing is needed, intrathecal administration of Etop-MNPs holds promise for magnetically-enhanced eradication of cancer cells distributed within CSF pathways, particularly if given early in the course of the disease.

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“…A diagnosis of leptomeningeal metastasis (LM) carries a poor prognosis with a median survival of only 2-4 months. 15 Few cases of LM caused by CRC have been reported. 16 Recently, it was found that CSF circulating tumor DNA (ctDNA) could better reflect the molecular characteristics than plasma ctDNA in patients with NSCLC harboring ALK rearrangement and may be useful in identifying drug targets and guiding treatment.…”

Section: Introductionmentioning

confidence: 99%