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Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment

Brain and leptomeningeal metastasis (LMM) of non-small cell lung cancer is still associated with poor prognosis. Moreover, the current diagnostic standard for LMM often yields false negative results and the scientific progress in this field is still unsatisfying. We present a case of a 71-year old p...

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Autores principales: Lüke, Florian, Blazquez, Raquel, Yamaci, Rezan Fahrioglu, Lu, Xin, Pregler, Benedikt, Hannus, Stefan, Menhart, Karin, Hellwig, Dirk, Wester, Hans-Jürgen, Kropf, Saskia, Heudobler, Daniel, Grosse, Jirka, Moosbauer, Jutta, Hutterer, Markus, Hau, Peter, Riemenschneider, Markus J., Bayerlová, Michaela, Bleckmann, Annalen, Polzer, Bernhard, Beißbarth, Tim, Klein, Christoph A., Pukrop, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922360/
https://www.ncbi.nlm.nih.gov/pubmed/29721166
http://dx.doi.org/10.18632/oncotarget.24787
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author Lüke, Florian
Blazquez, Raquel
Yamaci, Rezan Fahrioglu
Lu, Xin
Pregler, Benedikt
Hannus, Stefan
Menhart, Karin
Hellwig, Dirk
Wester, Hans-Jürgen
Kropf, Saskia
Heudobler, Daniel
Grosse, Jirka
Moosbauer, Jutta
Hutterer, Markus
Hau, Peter
Riemenschneider, Markus J.
Bayerlová, Michaela
Bleckmann, Annalen
Polzer, Bernhard
Beißbarth, Tim
Klein, Christoph A.
Pukrop, Tobias
author_facet Lüke, Florian
Blazquez, Raquel
Yamaci, Rezan Fahrioglu
Lu, Xin
Pregler, Benedikt
Hannus, Stefan
Menhart, Karin
Hellwig, Dirk
Wester, Hans-Jürgen
Kropf, Saskia
Heudobler, Daniel
Grosse, Jirka
Moosbauer, Jutta
Hutterer, Markus
Hau, Peter
Riemenschneider, Markus J.
Bayerlová, Michaela
Bleckmann, Annalen
Polzer, Bernhard
Beißbarth, Tim
Klein, Christoph A.
Pukrop, Tobias
author_sort Lüke, Florian
collection PubMed
description Brain and leptomeningeal metastasis (LMM) of non-small cell lung cancer is still associated with poor prognosis. Moreover, the current diagnostic standard for LMM often yields false negative results and the scientific progress in this field is still unsatisfying. We present a case of a 71-year old patient with an isolated LMM. While standard diagnostics could only diagnose a cancer of unknown primary, the use of [(68)Ga]-Pentixafor-PET/CT (CXCR4-PET/CT, a radiotracer targeting CXCR4) and a liquid biopsy of the cerebrospinal fluid revealed the primary NSCLC. The detection of L858R-EGFR, a common driver mutation in NSCLC, enabled us to treat the patient with Afatinib and monitor treatment using [(68)Ga]-Pentixafor PET/CT. To estimate the impact of CXCR4 signaling and its ligands in NSCLC brain metastasis we looked at their expression and correlation with EGFR mutations in a primary and brain metastasis data set and investigated the previously described binding of extracellular ubiquitin to CXCR4. In conclusion, we describe a novel approach to improve diagnostics towards LMM and underline the impact of the CXCL12/CXCR4 axis in brain metastasis in a subset of NSCLC patients. We cannot confirm a correlation of CXCR4 expression with EGFR mutations or the binding of extracellular ubiquitin as previously reported.
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spelling pubmed-59223602018-05-02 Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment Lüke, Florian Blazquez, Raquel Yamaci, Rezan Fahrioglu Lu, Xin Pregler, Benedikt Hannus, Stefan Menhart, Karin Hellwig, Dirk Wester, Hans-Jürgen Kropf, Saskia Heudobler, Daniel Grosse, Jirka Moosbauer, Jutta Hutterer, Markus Hau, Peter Riemenschneider, Markus J. Bayerlová, Michaela Bleckmann, Annalen Polzer, Bernhard Beißbarth, Tim Klein, Christoph A. Pukrop, Tobias Oncotarget Research Paper Brain and leptomeningeal metastasis (LMM) of non-small cell lung cancer is still associated with poor prognosis. Moreover, the current diagnostic standard for LMM often yields false negative results and the scientific progress in this field is still unsatisfying. We present a case of a 71-year old patient with an isolated LMM. While standard diagnostics could only diagnose a cancer of unknown primary, the use of [(68)Ga]-Pentixafor-PET/CT (CXCR4-PET/CT, a radiotracer targeting CXCR4) and a liquid biopsy of the cerebrospinal fluid revealed the primary NSCLC. The detection of L858R-EGFR, a common driver mutation in NSCLC, enabled us to treat the patient with Afatinib and monitor treatment using [(68)Ga]-Pentixafor PET/CT. To estimate the impact of CXCR4 signaling and its ligands in NSCLC brain metastasis we looked at their expression and correlation with EGFR mutations in a primary and brain metastasis data set and investigated the previously described binding of extracellular ubiquitin to CXCR4. In conclusion, we describe a novel approach to improve diagnostics towards LMM and underline the impact of the CXCL12/CXCR4 axis in brain metastasis in a subset of NSCLC patients. We cannot confirm a correlation of CXCR4 expression with EGFR mutations or the binding of extracellular ubiquitin as previously reported. Impact Journals LLC 2018-04-10 /pmc/articles/PMC5922360/ /pubmed/29721166 http://dx.doi.org/10.18632/oncotarget.24787 Text en Copyright: © 2018 Lüke et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lüke, Florian
Blazquez, Raquel
Yamaci, Rezan Fahrioglu
Lu, Xin
Pregler, Benedikt
Hannus, Stefan
Menhart, Karin
Hellwig, Dirk
Wester, Hans-Jürgen
Kropf, Saskia
Heudobler, Daniel
Grosse, Jirka
Moosbauer, Jutta
Hutterer, Markus
Hau, Peter
Riemenschneider, Markus J.
Bayerlová, Michaela
Bleckmann, Annalen
Polzer, Bernhard
Beißbarth, Tim
Klein, Christoph A.
Pukrop, Tobias
Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title_full Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title_fullStr Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title_full_unstemmed Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title_short Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR(mut) NSCLC in diagnosis, follow-up and treatment
title_sort isolated metastasis of an egfr-l858r-mutated nsclc of the meninges: the potential impact of cxcl12/cxcr4 axis in egfr(mut) nsclc in diagnosis, follow-up and treatment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922360/
https://www.ncbi.nlm.nih.gov/pubmed/29721166
http://dx.doi.org/10.18632/oncotarget.24787
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