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Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases.

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Title: Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases.
Authors: Khaled, Mariam Lotfy, Tarhini, Ahmad A., Forsyth, Peter A., Smalley, Inna, Piña, Yolanda
Source: Cancers; Mar2023, Vol. 15 Issue 6, p1884, 19p
Subject Terms: IMMUNE checkpoint inhibitors, MELANOMA, METASTASIS, CELL physiology, APOPTOSIS, CANCER, CANCER patients, PROTEOMICS, MENINGES, CEREBROSPINAL fluid, CELL lines, IMMUNOTHERAPY
Abstract: Simple Summary: Leptomeningeal disease in melanoma (LMM) patients is characterized by aggressiveness and dismal outcomes. Clinical studies and case reports demonstrate the potential of immune and targeted therapies (especially in combinatorial or multi-modal settings) in improving survival for some patients; however, LMM still progresses rapidly in most patients regardless of treatment. Several recent studies have characterized the melanoma microenvironment within the CSF compartment and improved the basic understanding of the biology of LMM. Additional laboratory and clinical studies are necessary to substantiate the relevance of different therapies and their impact on melanoma within the leptomeningeal microenvironment. Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5–15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3–6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4+ T-cells, myeloid-derived suppressor cells, and a low number of CD8+ T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood–CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors. This review summarizes the biology and anatomic features of melanoma LMD, as well as the current therapeutic approaches. [ABSTRACT FROM AUTHOR]
Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
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  Label: Title
  Group: Ti
  Data: Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Khaled%2C+Mariam+Lotfy%22">Khaled, Mariam Lotfy</searchLink><br /><searchLink fieldCode="AR" term="%22Tarhini%2C+Ahmad+A%2E%22">Tarhini, Ahmad A.</searchLink><br /><searchLink fieldCode="AR" term="%22Forsyth%2C+Peter+A%2E%22">Forsyth, Peter A.</searchLink><br /><searchLink fieldCode="AR" term="%22Smalley%2C+Inna%22">Smalley, Inna</searchLink><br /><searchLink fieldCode="AR" term="%22Piña%2C+Yolanda%22">Piña, Yolanda</searchLink>
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  Data: Cancers; Mar2023, Vol. 15 Issue 6, p1884, 19p
– Name: Subject
  Label: Subject Terms
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  Data: <searchLink fieldCode="DE" term="%22IMMUNE+checkpoint+inhibitors%22">IMMUNE checkpoint inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22MELANOMA%22">MELANOMA</searchLink><br /><searchLink fieldCode="DE" term="%22METASTASIS%22">METASTASIS</searchLink><br /><searchLink fieldCode="DE" term="%22CELL+physiology%22">CELL physiology</searchLink><br /><searchLink fieldCode="DE" term="%22APOPTOSIS%22">APOPTOSIS</searchLink><br /><searchLink fieldCode="DE" term="%22CANCER%22">CANCER</searchLink><br /><searchLink fieldCode="DE" term="%22CANCER+patients%22">CANCER patients</searchLink><br /><searchLink fieldCode="DE" term="%22PROTEOMICS%22">PROTEOMICS</searchLink><br /><searchLink fieldCode="DE" term="%22MENINGES%22">MENINGES</searchLink><br /><searchLink fieldCode="DE" term="%22CEREBROSPINAL+fluid%22">CEREBROSPINAL fluid</searchLink><br /><searchLink fieldCode="DE" term="%22CELL+lines%22">CELL lines</searchLink><br /><searchLink fieldCode="DE" term="%22IMMUNOTHERAPY%22">IMMUNOTHERAPY</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Simple Summary: Leptomeningeal disease in melanoma (LMM) patients is characterized by aggressiveness and dismal outcomes. Clinical studies and case reports demonstrate the potential of immune and targeted therapies (especially in combinatorial or multi-modal settings) in improving survival for some patients; however, LMM still progresses rapidly in most patients regardless of treatment. Several recent studies have characterized the melanoma microenvironment within the CSF compartment and improved the basic understanding of the biology of LMM. Additional laboratory and clinical studies are necessary to substantiate the relevance of different therapies and their impact on melanoma within the leptomeningeal microenvironment. Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5–15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3–6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4<superscript>+</superscript> T-cells, myeloid-derived suppressor cells, and a low number of CD8<superscript>+</superscript> T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood–CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors. This review summarizes the biology and anatomic features of melanoma LMD, as well as the current therapeutic approaches. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.3390/cancers15061884
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      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 19
        StartPage: 1884
    Subjects:
      – SubjectFull: IMMUNE checkpoint inhibitors
        Type: general
      – SubjectFull: MELANOMA
        Type: general
      – SubjectFull: METASTASIS
        Type: general
      – SubjectFull: CELL physiology
        Type: general
      – SubjectFull: APOPTOSIS
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      – SubjectFull: CANCER
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      – SubjectFull: CANCER patients
        Type: general
      – SubjectFull: PROTEOMICS
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      – SubjectFull: CEREBROSPINAL fluid
        Type: general
      – SubjectFull: CELL lines
        Type: general
      – SubjectFull: IMMUNOTHERAPY
        Type: general
    Titles:
      – TitleFull: Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases.
        Type: main
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          Name:
            NameFull: Khaled, Mariam Lotfy
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            NameFull: Tarhini, Ahmad A.
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            NameFull: Forsyth, Peter A.
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            NameFull: Smalley, Inna
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            NameFull: Piña, Yolanda
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            – D: 15
              M: 03
              Text: Mar2023
              Type: published
              Y: 2023
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