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 1 , Raquel Blazquez 1 , Rezan Fahrioglu Yamaci 2 , Xin Lu 2 , Benedikt Pregler 3 , Stefan Hannus 4 , Karin Menhart 5 , Dirk Hellwig 5 , Hans-Jürgen Wester 6 , Saskia Kropf 7 , Daniel Heudobler 1 , Jirka Grosse 5 , Jutta Moosbauer 5 , Markus Hutterer 8 , 9 , 10 , Peter Hau 8 , 9 , Markus J. Riemenschneider 11 , Michaela Bayerlová 12 , Annalen Bleckmann 12, 13 , Bernhard Polzer 14 , Tim Beißbarth 12 , Christoph A. Klein 2, 14 and Tobias Pukrop 1 1 Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany 2 Chair of Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany 3 Institute of Radiology, University Hospital Regensburg, Regensburg, Germany 4 Intana Bioscience GmbH, Martinsried, Germany 5 Department of Nuclear Medicine, University Hospital Regensburg, Regensburg, Germany 6 Chair of Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany 7 SCINTOMICS GmbH, Fuerstenfeldbruck, Germany 8 Department of Neurology, University Hospital Regensburg, Regensburg, Germany 9 Wilhelm Sander-Neurooncology Unit, University Hospital Regensburg, Regensburg, Germany 10 Department of Neurology 1, NeuroMed Campus, Kepler University Hospital Linz, Linz, Austria 11 Department of Neuropathology, University Hospital Regensburg, Regensburg, Germany 12 University Medical Center Göttingen, Department of Medical Statistics, Göttingen, Germany 13 University Medical Center Göttingen, Department of Hematology and Oncology, Göttingen, Germany 14 Division Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany Correspondence to: Tobias Pukrop, email: tobias.pukrop@ukr.de Keywords: NSCLC; brain metastasis; pentixafor PET/CT; CXCR4; fluorescence cross correlation spectroscopy Received: November 16, 2017 Accepted: February 27, 2018 Published: April 10, 2018 ABSTRACT 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.