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De-Colle, Chiara; Menegakis, Apostolos; Moennich, David; Welz, Stefan; Boeke, Simon; Sipos, Bence; Fend, Falko; Mauz, Paul-Stefan; Tinhofer, Inge; Budach, Volker; Abu Jawad, Jehad; Stuschke, Martin; Balermpas, Panagiotis; Rodel, Claus; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Belka, Claus; Ganswindt, Ute; Pigorsch, Steffi; Combs, Stephanie E.; Lohaus, Fabian; Linge, Annett; Krause, Mechthild; Baumann, Michael; Zips, Daniel (2018): SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy. In: Radiotherapy and Oncology, Vol. 126, No. 1: pp. 125-131
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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.