Diagnostic significance of cerebrospinal fluid EGFR mutation analysis for leptomeningeal metastasis in non-small-cell lung cancer patients harboring an active EGFR mutation following gefitinib therapy failure

Sasaki, Shin‐ichi; Yoshioka, Yasuko; Ko, Ryo; Katsura, Yoko; Namba, Yukiko; Shukuya, Takehito; Kido, Koichi; Iwakami, Shin‐ichiro; Tominaga, Shigeru; Takahashi, Kazuhisa

doi:10.1016/j.resinv.2015.07.001

Cited by 48 publications

(32 citation statements)

References 28 publications

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“…Though we cannot fully exclude the possibility that concurrent systemic/intrathecal chemotherapy or WBRT may suppress acquiring of the T790M resistance mutation, our results are consistent with previous reports demonstrating that the emergence of T790M in CNS lesions was relatively rare comparing to extracranial sites (24)(25)(26). This can probably partially be explained by the low exposure of first-generation EGFR-TKIs in CSF due to poor BBB penetration property (26), so that intracranial tumor cells are shielded from the effects of compounds and thus will not readily acquire the secondary T790M gatekeeper mutation.…”

Section: Discussionsupporting

confidence: 90%

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Fan

Zhu²,

et al. 2018

Clinical Cancer Research

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Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood.Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM.Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development.Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

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Section: Discussionsupporting

confidence: 90%

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Fan

Zhu²,

et al. 2018

Clinical Cancer Research

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“…In previous years, the most common diagnostic tools for lung cancer included CT, X-chip imaging, and sputum cytology examination. However, these methods lack sensitivity and specificity, and often lead to misdiagnosis (Sasaki et al, 2016;Zaric et al, 2016). Currently, medical imaging, bronchoscopy, bronchial perfusion fluid examinations, and tissue pathology analyses are widely used in lung cancer screening and early diagnosis (Huang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis

Pan¹,

Zhou²,

Wang³

et al. 2016

Genet. Mol. Res.

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“…Sixteen patients were positive for activating EGFR mutations and the sensitivity of CSF for EGFR mutations was 67% with a specificity of 82%. Another study retrospectively analyzed the CSF of seven EGFR mutant NSCLC patients who had developed leptomeningeal disease during or after therapy with gefitinib (50). The EGFR mutation detected in all cases was the same as that detected in the primary tumor whereas cytology was positive in only two patients.…”

Section: Ctdna In Other Body Fluidsmentioning

confidence: 99%

Circulating DNA in EGFR-mutated lung cancer

Singh¹,

Li²,

Cheng³

2017

Ann. Transl. Med.

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Circulating tumor DNA (ctDNA) consists of short double stranded DNA fragments that are released by tumors including non-small cell lung cancer (NSCLC). With the identification of driver mutations in the epidermal growth factor receptor (EGFR) gene and development of targeted tyrosine kinase inhibitors (TKIs), the clinical outcome of NSCLC patients in this subgroup has improved tremendously.The gold standard to assess EGFR mutation is through tissue biopsy, which can be limited by difficulty in accessing the tumor, inability of patients to tolerate invasive procedures, insufficient sample for molecular testing and inability to capture intratumoral heterogeneity. The great need for rapid and accurate identification of activating EGFR mutations in NSCLC patients paves the road for ctDNA technology.Studies have demonstrated ctDNA to be a reliable complement to tumor genotyping. Platforms like digital polymerase chain reaction (PCR) and next-generation sequencing based analyses have made it possible to identify EGFR mutations in plasma with high sensitivity and specificity. This article will provide an overview on ctDNA in the context of EGFR mutated NSCLC, especially its emerging applications in diagnosis, disease surveillance, treatment monitoring and detection of resistance mechanisms.

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Diagnostic significance of cerebrospinal fluid EGFR mutation analysis for leptomeningeal metastasis in non-small-cell lung cancer patients harboring an active EGFR mutation following gefitinib therapy failure

Cited by 48 publications

References 28 publications

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis

Circulating DNA in EGFR-mutated lung cancer

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