Osimertinib Quantitative and Gene Variation Analyses in Cerebrospinal Fluid and Plasma of a Non-small Cell Lung Cancer Patient with Leptomeningeal Metastases
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Leptomeningeal metastases (LM) are much more frequent in patients of non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI) shows promising efficacy for LM.
OBJECTIVE: The aim of this study was to analyze the concentration of osimertinib and gene variation of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF). Furthermore, we explored whether ctDNA in CSF might be used as a biomarker to predict and monitor therapeutic responses.
METHODS: The dynamic paired CSF and blood samples were collected from the NSCLC patient with LM acquired EGFR-TKI resistance. A method based on ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) was developed and validated for detecting osimertinib in CSF and plasma samples. Gene variations of ctDNA were tested by next-generation sequencing with a panel of 1021 genes.
RESULTS: The concentrations of osimertinib in CSF were significantly lower than that in plasma (penetration rate was 1.47%). Mutations included mTOR, EGFR, CHECK1, ABCC11, and TP53 were explored in ctDNA from plasma and CSF samples. The detected mutation rate of CSF samples was higher than that of plasma samples (50% vs. 25%). Our data further revealed that the variations allele frequency (VAF) and molecular tumor burden index (mTBI) of ctDNA derived from CSF exhibited the negative correlation with efficacy of treatment.
CONCLUSION: ctDNA from CSF might be a useful biomarker for monitoring the efficacy of treatment and an effective complement to nuclear magnetic resonance imaging (MRI) for LM.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Current cancer drug targets - 19(2019), 8 vom: 19., Seite 666-673 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Song, Yuanyuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.09.2020 Date Revised 03.06.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1568009618666181017114111 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM289676126 |
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| 100 | 1 | |a Song, Yuanyuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Osimertinib Quantitative and Gene Variation Analyses in Cerebrospinal Fluid and Plasma of a Non-small Cell Lung Cancer Patient with Leptomeningeal Metastases |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Revised 03.06.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Leptomeningeal metastases (LM) are much more frequent in patients of non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI) shows promising efficacy for LM | ||
| 520 | |a OBJECTIVE: The aim of this study was to analyze the concentration of osimertinib and gene variation of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF). Furthermore, we explored whether ctDNA in CSF might be used as a biomarker to predict and monitor therapeutic responses | ||
| 520 | |a METHODS: The dynamic paired CSF and blood samples were collected from the NSCLC patient with LM acquired EGFR-TKI resistance. A method based on ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) was developed and validated for detecting osimertinib in CSF and plasma samples. Gene variations of ctDNA were tested by next-generation sequencing with a panel of 1021 genes | ||
| 520 | |a RESULTS: The concentrations of osimertinib in CSF were significantly lower than that in plasma (penetration rate was 1.47%). Mutations included mTOR, EGFR, CHECK1, ABCC11, and TP53 were explored in ctDNA from plasma and CSF samples. The detected mutation rate of CSF samples was higher than that of plasma samples (50% vs. 25%). Our data further revealed that the variations allele frequency (VAF) and molecular tumor burden index (mTBI) of ctDNA derived from CSF exhibited the negative correlation with efficacy of treatment | ||
| 520 | |a CONCLUSION: ctDNA from CSF might be a useful biomarker for monitoring the efficacy of treatment and an effective complement to nuclear magnetic resonance imaging (MRI) for LM | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cerebrospinal fluid | |
| 650 | 4 | |a Leptomeningeal metastases | |
| 650 | 4 | |a Next-generation sequencing | |
| 650 | 4 | |a Non-small cell lung cancer | |
| 650 | 4 | |a Osimertinib | |
| 650 | 4 | |a Plasma | |
| 650 | 4 | |a UPLC-MS/MS. | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a Circulating Tumor DNA |2 NLM | |
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| 700 | 1 | |a Liu, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Yanfang |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Xiaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yuankai |e verfasserin |4 aut | |
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