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SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy
Authors:Chiara De-Colle  Apostolos Menegakis  David Mönnich  Stefan Welz  Simon Boeke  Bence Sipos  Falko Fend  Paul-Stefan Mauz  Inge Tinhofer  Volker Budach  Jehad Abu Jawad  Martin Stuschke  Panagiotis Balermpas  Claus Rödel  Anca-Ligia Grosu  Amir Abdollahi  Jürgen Debus  Claus Belka  Daniel Zips
Affiliation:1. Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany;2. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site Tübingen, Germany;3. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Berlin, Germany;4. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Dresden, Germany;5. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Essen, Germany;6. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Frankfurt, Germany;g. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Freiburg, Germany;h. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Heidelberg, Germany;i. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site ?Munich, Germany;j. Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany;k. Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany;l. Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany;m. Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Germany;n. Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany;o. Department of Radiation Oncology, University of Freiburg, Germany;p. Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany;q. Heidelberg Ion Therapy Center (HIT), Department of Radiation Oncology, University of Heidelberg Medical School, Germany;r. National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany;s. Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany;t. Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany;u. Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany;v. Department of Radiation Oncology, Technische Universität München, Germany.;w. Institute for Innovative radiation therapy in Helmholtz-Zentrum München, Germany;x. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany;y. OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Germany;z. National Center for Tumor Diseases (NCT), partner site Dresden, Germany;11. Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology – OncoRay, Germany;12. German Cancer Research Center (DKFZ), Heidelberg, Germany
Abstract:

Introduction

Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT).

Material and methods

Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence. SDF-1 and CXCR4 expression was correlated with clinico-pathological characteristics and outcome after RT-CT.

Results

Patients with tumours exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for loco-regional relapse and a worse overall survival after RT-CT (multivariate analysis, hazard ratio 2.33, CI [1.18–4.62], p?=?0.02 and hazard ratio 2.02, CI [1.13–3.59], p?=?0.02, respectively). Similar results were observed when only the subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16, p?=?0.02 and p?=?0.01, respectively).

Conclusions

Our data support the importance of SDF-1 and CXCR4 expression for loco-regional control and overall survival in HNSCC after primary radiochemotherapy. Prospective multivariate validation and further studies into CXCR4 inhibition to overcome radiation resistance are warranted.
Keywords:SDF-1  CXCR4  Head and neck cancer  Prognostic  Biomarker  Primary radiochemotherapy
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