SDF-1/CXCR4 as prognostic markers for postoperative radiochemotherapy in head and neck cancer

Abstract

Outcomes of patients affected by locally advanced head and neck squamous cell carcinomas (HNSCC) and treated with surgery and adjuvant radio-chemotherapy are still unsatisfactory, being the overall survival (OS) still settled around 50% at five years, with poor outcomes especially among HPV negative patients. Therefore, patients’ stratification based on biomarker profiles is required for personalised therapies. SDF-1/CXCR4 is known as the most important chemokine pathway involved in tumour development, progression and metastasis. Nevertheless, no clear data exist regarding the role of SDF-1/CXCR4 among HNSCC patients. The present study aims to investigate the prognostic value of SDF-1 and CXCR4 in a large and homogeneous cohort of HNSCC patients treated with post-operative RT-CT, as part of a multicentre biomarker study within the German Cancer Consortium Radiation Oncology Group. The results of the study have been published [1]. 221 patients affected by stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with surgery and adjuvant RT-CT. Tumour microarrays with the post-surgical tumour material were generated and stained for SDF-1 and CXCR4 using immunofluorescence. 201 patients were analysed for SDF-1 and 190 for CXCR4. The univariate and multivariate analyses showed that higher SDF-1 intracellular expression significantly correlated with poor locoregional control (LRC) in the whole patients’ cohort as well as in the HPV16 negative patients. Higher CXCR4 intracellular expression correlated with poor LRC in the univariate analysis, but this trend was not confirmed in the multivariate analysis. Not high SDF-1 nor high CXCR4 expression correlated with distant metastasis free survival or OS. In summary, we could show for the first time in a large and homogeneous cohort of HNSCC patients treated with adjuvant RT-CT that SDF-1 correlates with worse LRC. These results are exploratory and need to be validated prospectively, but support further investigation of SDF-1/CXCR4 as potential biomarker for treatment individualization and as a target to overcome resistance to RT.