Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Shah, Binay Kumar; Pak, Isaac; Budhathoki, Nibash; Buker, Kayla

doi:10.21147/j.issn.1000-9604.2017.06.08

Cited by 10 publications

(5 citation statements)

References 49 publications

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“…Surgical intervention can be considered for symptom control in diffuse leptomeningeal involvement and in the setting of solitary parenchymal or leptomeningeal lesions [11]. In this modern era, the use of targeted therapies to treat LCM in non-small cell lung cancer has shown survival benefits with better safety profiles [12]. A recent singlearm, open-label phase two trial of pembrolizumab in patients of solid tumor malignancies with leptomeningeal carcinomatosis was also published in June 2020.…”

Section: Discussionmentioning

confidence: 99%

Leptomeningeal Carcinomatosis in Epithelial Ovarian Cancer: A Diagnostic Challenge

Tahir

Ram

Jain

et al. 2021

Cureus

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Leptomeningeal carcinomatosis (LCM), also known as neoplastic meningitis, is a rare entity. It is generally seen in solid tumors. Ovarian cancers can infrequently cause LCM. The clinical presentation is variable. Diagnosis is made by a lumbar puncture that shows malignant cells in the cerebrospinal fluid (CSF) and usually correlates with imaging findings. Given the low individual sensitivities of lumbar puncture (55%) and magnetic resonance imaging (70%), it is recommended to combine both modalities for optimal diagnostic results. Treatment options vary depending on the type of primary carcinoma, however, the prognosis is guarded. We report a case of LCM in a patient with stage IV epithelial ovarian cancer in remission, which became a diagnostic challenge due to a lack of imaging findings.

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Section: Discussionmentioning

confidence: 99%

Leptomeningeal Carcinomatosis in Epithelial Ovarian Cancer: A Diagnostic Challenge

Tahir

Ram

Jain

et al. 2021

Cureus

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“…In recent years, molecular targeted therapy for cancer has been increasing ( 30 , 31 ). Its greatest advantage is that it can specifically act on the corresponding molecular targets without obvious side effects on other tissues.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of epidermal growth factor receptor variant III expression and nuclear translocation in Chinese human gliomas

Yang¹,

Ren²,

Tao³

et al. 2019

Chinese Journal of Cancer Research

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ObjectiveTo determine the prognostic implications and clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression and EGFRvIII nuclear translocation in Chinese human gliomas.MethodsWe retrospectively examined EGFRvIII expression and EGFRvIII nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization (WHO) II gliomas, 84 WHO III gliomas and 72 glioblastomas (WHO IV). Factors that correlated with EGFRvIII and EGFRvIII nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.ResultsLog-rank tests showed that patient age, Karnofsky performance scale (KPS) score, tumor grade, EGFRvIII expression, EGFRvIII nuclear translocation, 1p/19q codeletion, isocitrate dehydrogenase (IDH) mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase (MGMT) status (P<0.05) were significantly correlated with overall survival (OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvIII nuclear translocation, 1p/19q codeletion, and IDH mutation (P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvIII nuclear translocation (≥7%) had both significantly shorter OS [hazard ratio (HR): 1.920, 95% confidence interval (95% CI): 1.228−3.003, P=0.004] and progression-free survival (PFS) times (HR: 1.661, 95% CI: 1.116−2.471, P=0.012) than those with a low level of EGFRvIII nuclear translocation (<7%).ConclusionsA high level of EGFRvIII nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvIII expression is not an independent clinical prognostic factor. The level of EGFRvIII nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.

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“…Lung cancer is one of the most common causes of LM (5), of which adenocarcinoma accounts for 84-96% (6). Incidence is increasing in lung adenocarcinoma patients because of improved survival from new molecular targeted therapies (7). However, the diagnosis and disease course monitoring for LM are still challenging.…”

Section: Introductionmentioning

confidence: 99%

Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

Pan

Yang

et al. 2020

Front. Oncol.

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Background: Leptomeningeal metastasis (LM) has frequently been observed in patients with lung adenocarcinoma. So far, its diagnosis and disease course monitoring are still extremely difficult. Moreover, there is no effective treatment regimen for LM due to a lack knowledge on the molecular mechanism of LM. This study aimed to identify LM-related cerebrospinal fluid (CSF) miRNAs, which have potential value for diagnosing and monitoring LM and exploring the molecular mechanism. Methods: CSF miRNAs were screened and verified by microarray analysis and quantitative real-time PCR (qRT-PCR) in LM patients with lung adenocarcinoma and non-LM controls, and the diagnostic performance of candidate miRNAs was evaluated. Then, candidate miRNAs in matched CSF samples from LM patients at diagnosis, after initial therapy, at relapse, and after salvage therapy, were analyzed to assess the relationship between CSF miRNAs and LM disease course. The effect of candidate miRNAs on proliferation, invasion, and migration of lung adenocarcinoma cell lines was assessed. The targeted genes of the candidate miRNA were predicted by TargetScan, miRDB, and miRTarbase online analysis tools. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functional categories of predicted target genes. Results: CSF miR-7975, miR-7977, and miR-7641 were screened and verified to be statistically significantly up-regulated in LM patients compared to non-LM controls. The three miRNAs, when combined, exhibited optimal diagnostic performance. Longitudinal data of CSF miR-7975 and miR-7977 correlated well with clinical courses of LM. Overexpression of miR-7977 promoted proliferation, migration, and invasion of lung adenocarcinoma cells. Moreover, 385 targeted genes of miR-7977 were predicted and were involved in various pathways related to cancer metastasis. Conclusions: This study offers insights for future research of CSF miRNAs as robust tools for diagnosing and monitoring LM. It also reveals a novel pathway for exploration of underlying mechanisms of LM.

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Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Cited by 10 publications

References 49 publications

Leptomeningeal Carcinomatosis in Epithelial Ovarian Cancer: A Diagnostic Challenge

Leptomeningeal Carcinomatosis in Epithelial Ovarian Cancer: A Diagnostic Challenge

Prognostic implications of epidermal growth factor receptor variant III expression and nuclear translocation in Chinese human gliomas

Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

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