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 [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.

Highlights

  • Brain metastasis (BM) and lepto-meningeal metastasis (LMM) of non-small cell lung cancer (NSCLC) is a severe clinical problem with significant impact on quality of life (QoL) and overall survival (OS)

  • To estimate the impact of Chemokine Receptor 4 (CXCR4) signaling and its ligands in NSCLC brain metastasis we looked at their expression and correlation with Epithelilal Growth Factor Receptor (EGFR) mutations in a primary and brain metastasis data set and investigated the previously described binding of extracellular ubiquitin to CXCR4

  • Three cells with highest Desoxyribonuclear Acid (DNA) quality (GII4) were selected for targeted sequencing of EGFR Exon 21 and we identified an EGFR-L858R missense mutation that is common in adenocarcinoma of NSCLC in two out of three disseminated cancer cells (DCC) (Figure 2B, Supplementary Figure 2)

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Summary

Introduction

Brain metastasis (BM) and lepto-meningeal metastasis (LMM) of non-small cell lung cancer (NSCLC) is a severe clinical problem with significant impact on quality of life (QoL) and overall survival (OS). Especially LMM requires more intensive scientific attention, because even diagnosing LMM is often difficult. This is especially true, when the disease presents in an occult fashion, if tumor material is difficult to reach for the acquisition of histologic material or the patient’s condition does not allow invasive procedures. For these scenarios, innovative, minimallyinvasive diagnostic strategies are needed, especially in the era of “precision medicine” where a molecular diagnosis is obligatory for targeted therapy of NSCLC patients

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