Research Papers:

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

Florian Lüke, Raquel Blazquez, Rezan Fahrioglu Yamaci, Xin Lu, Benedikt Pregler, Stefan Hannus, Karin Menhart, Dirk Hellwig, Hans-Jürgen Wester, Saskia Kropf, Daniel Heudobler, Jirka Grosse, Jutta Moosbauer, Markus Hutterer, Peter Hau, Markus J. Riemenschneider, Michaela Bayerlová, Annalen Bleckmann, Bernhard Polzer, Tim Beißbarth, Christoph A. Klein and Tobias Pukrop _

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Oncotarget. 2018; 9:18844-18857. https://doi.org/10.18632/oncotarget.24787

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Florian Lüke1, Raquel Blazquez1, Rezan Fahrioglu Yamaci2, Xin Lu2, Benedikt Pregler3, Stefan Hannus4, Karin Menhart5, Dirk Hellwig5, Hans-Jürgen Wester6, Saskia Kropf7, Daniel Heudobler1, Jirka Grosse5, Jutta Moosbauer5, Markus Hutterer8,9,10, Peter Hau8,9, Markus J. Riemenschneider11, Michaela Bayerlová12, Annalen Bleckmann12,13, Bernhard Polzer14, Tim Beißbarth12, Christoph A. Klein2,14 and Tobias Pukrop1

1Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany

2Chair of Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany

3Institute of Radiology, University Hospital Regensburg, Regensburg, Germany

4Intana Bioscience GmbH, Martinsried, Germany

5Department of Nuclear Medicine, University Hospital Regensburg, Regensburg, Germany

6Chair of Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany

7SCINTOMICS GmbH, Fuerstenfeldbruck, Germany

8Department of Neurology, University Hospital Regensburg, Regensburg, Germany

9Wilhelm Sander-Neurooncology Unit, University Hospital Regensburg, Regensburg, Germany

10Department of Neurology 1, NeuroMed Campus, Kepler University Hospital Linz, Linz, Austria

11Department of Neuropathology, University Hospital Regensburg, Regensburg, Germany

12University Medical Center Göttingen, Department of Medical Statistics, Göttingen, Germany

13University Medical Center Göttingen, Department of Hematology and Oncology, Göttingen, Germany

14Division Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany

Correspondence to:

Tobias Pukrop, email: [email protected]

Keywords: NSCLC; brain metastasis; pentixafor PET/CT; CXCR4; fluorescence cross correlation spectroscopy

Received: November 16, 2017     Accepted: February 27, 2018     Published: April 10, 2018


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 [68Ga]-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 [68Ga]-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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