Metastatic Melanoma With Leptomeningeal Disease

Marinova, Amanda M; Reilly, Jennifer L; Wong, Victoria; Weiss, Stéphanie; Olszanski, Anthony J.

doi:10.6004/jadpro.2021.12.1.6

Cited by 3 publications

(4 citation statements)

References 8 publications

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“…The search yielded 289 citations, of which 14 were included in the qualitative synthesis (Supplementary File 1). Nine were case-reports, four were retrospective case-series (including 32 patients), and one was a single-arm phase-II trial (including 20 patients); levels of evidence were V, IV, and IIb, respectively (Supplementary File 2) (8)(9)(10)(11)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Critical appraisal resulted in low risk of bias for all included articles (Supplementary File 3).…”

Section: Resultsmentioning

confidence: 99%

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

et al. 2021

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Section: Resultsmentioning

confidence: 99%

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

et al. 2021

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“…LMM can occur at any age, and while the risk of melanoma increases as we age, on average, patients are diagnosed with melanoma at the age of 65 [ 75 ]. The prognosis for patients with LMM remains grim at 17–22 weeks despite advancements in treatment [ 73 , 74 , 76 ]. There are exceptions to this survival duration range, as exemplified by a case report from Marinova et al, demonstrating that a 43-year-old patient with BRAF-positive stage IIIa melanoma was responsive to radiation and immunotherapy.…”

Section: Melanomamentioning

confidence: 99%

“…There are exceptions to this survival duration range, as exemplified by a case report from Marinova et al, demonstrating that a 43-year-old patient with BRAF-positive stage IIIa melanoma was responsive to radiation and immunotherapy. The patient continued to survive for 2.5 years with neurological symptoms [ 76 ]. Many patients with LMM fail to respond to treatment and often die from severe systemic disease burden, tumor progression, and medication toxicity.…”

Section: Melanomamentioning

confidence: 99%

“…Many patients with LMM fail to respond to treatment and often die from severe systemic disease burden, tumor progression, and medication toxicity. It has been theorized that the advancement of melanoma treatment has led to an increase in the incidence of LMM because the CSF serves as a sanctuary for cancer cells given that it is a protected environment from systemic therapy [ 73 , 76 ].…”

Section: Melanomamentioning

confidence: 99%

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Leptomeningeal Metastasis: A Review of the Pathophysiology, Diagnostic Methodology, and Therapeutic Landscape

Nguyen

Dada

et al. 2023

Current Oncology

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The present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer types. For our purposes, the focused metastatic malignancies include breast cancer, lung cancer, melanoma, primary central nervous system tumors, and hematologic cancers (lymphoma, leukemia, and multiple myeloma). Of note, our discussion was limited to cancer-specific leptomeningeal metastases secondary to the aforementioned primary cancers. LMD mechanisms secondary to non-cancerous pathologies, such as infection or inflammation of the leptomeningeal layer, were excluded from our scope of review. Furthermore, we intended to characterize general leptomeningeal disease, including the specific anatomical infiltration process/area, CSF dissemination, manifesting clinical symptoms in patients afflicted with the disease, detection mechanisms, imaging modalities, and treatment therapies (both preclinical and clinical). Of these parameters, leptomeningeal disease across different primary cancers shares several features. Pathophysiology regarding the development of CNS involvement within the mentioned cancer subtypes is similar in nature and progression of disease. Consequently, detection of leptomeningeal disease, regardless of cancer type, employs several of the same techniques. Cerebrospinal fluid analysis in combination with varied imaging (CT, MRI, and PET-CT) has been noted in the current literature as the gold standard in the diagnosis of leptomeningeal metastasis. Treatment options for the disease are both varied and currently in development, given the rarity of these cases. Our review details the differences in leptomeningeal disease as they pertain through the lens of several different cancer subtypes in an effort to highlight the current state of targeted therapy, the potential shortcomings in treatment, and the direction of preclinical and clinical treatments in the future. As there is a lack of comprehensive reviews that seek to characterize leptomeningeal metastasis from various solid and hematologic cancers altogether, the authors intended to highlight not only the overlapping mechanisms but also the distinct patterning of disease detection and progression as a means to uniquely treat each metastasis type. The scarcity of LMD cases poses a barrier to more robust evaluations of this pathology. However, as treatments for primary cancers have improved over time, so has the incidence of LMD. The increase in diagnosed cases only represents a small fraction of LMD-afflicted patients. More often than not, LMD is determined upon autopsy. The motivation behind this review stems from the increased capacity to study LMD in spite of scarcity or poor patient prognosis. In vitro analysis of leptomeningeal cancer cells has allowed researchers to approach this disease at the level of cancer subtypes and markers. We ultimately hope to facilitate the clinical translation of LMD research through our discourse.

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Leptomeningeal Metastases: New Opportunities in the Modern Era

Wilcox

Boire

2022

Neurotherapeutics

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Leptomeningeal metastases arise from cancer cell entry into the subarachnoid space, inflicting significant neurologic morbidity and mortality across a wide range of malignancies. The modern era of cancer therapeutics has seen an explosion of molecular-targeting agents and immune-mediated strategies for patients with breast, lung, and melanoma malignancies, with meaningful extracranial disease control and improvement in patient survival. However, the clinical efficacy of these agents in those with leptomeningeal metastases remains understudied, due to the relative rarity of this patient population, the investigational challenges associated with studying this dynamic disease state, and brisk disease pace. Nevertheless, retrospective studies, post hoc analyses, and small prospective trials in the last two decades provide a glimmer of hope for patients with leptomeningeal metastases, suggesting that several cancer-directed strategies are not only active in the intrathecal space but also improve survival against historical odds. The continued development of clinical trials devoted to patients with leptomeningeal metastases is critical to establish robust efficacy outcomes in this patient population, define drug pharmacokinetics in the intrathecal space, and uncover new avenues for treatment in the face of leptomeningeal therapeutic resistance.

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Metastatic Melanoma With Leptomeningeal Disease

Cited by 3 publications

References 8 publications

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

Leptomeningeal Metastasis: A Review of the Pathophysiology, Diagnostic Methodology, and Therapeutic Landscape

Leptomeningeal Metastases: New Opportunities in the Modern Era

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