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HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell c...

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Main Authors: Linge, Annett (Author) , Lohaus, Fabian (Author) , Löck, Steffen (Author) , Nowak, Alexander (Author) , Gudziol, Volker (Author) , Valentini, Chiara (Author) , Neubeck, Cläre von (Author) , Jütz, Martin (Author) , Tinhofer, Ingeborg (Author) , Budach, Volker (Author) , Sak, Ali (Author) , Stuschke, Martin (Author) , Balermpas, Panagiotis (Author) , Rödel, Claus (Author) , Grosu, Anca-Ligia (Author) , Abdollahi, Amir (Author) , Debus, Jürgen (Author) , Ganswindt, Ute (Author) , Belka, Claus (Author) , Pigorsch, Steffi Ulrike (Author) , Combs, Stephanie (Author) , Mönnich, David (Author) , Zips, Daniel (Author) , Buchholz, Frank (Author) , Aust, Daniela E. (Author) , Baretton, Gustavo Bruno (Author) , Thames, Howard D. (Author) , Dubrovska, Anna (Author) , Alsner, Jan (Author) , Overgaard, Jens (Author) , Krause, Mechthild (Author) , Baumann, Michael (Author)
Format: Article (Journal)
Language:English
Published: 29 November 2016
In: Radiotherapy and oncology
Year: 2016, Volume: 121, Issue: 3, Pages: 364-373
ISSN:1879-0887
DOI:10.1016/j.radonc.2016.11.008
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.radonc.2016.11.008
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Author Notes:Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E. Aust, Gustavo B. Baretton, Howard D. Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann, for the DKTK-ROG

MARC

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245 1 0 |a HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy  |b a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)  |c Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E. Aust, Gustavo B. Baretton, Howard D. Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann, for the DKTK-ROG 
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520 |a OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). - MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed. The primary endpoint of this study was loco-regional control (LRC). - RESULTS: Univariate Cox regression revealed a significant impact of tumour volume, p16 overexpression, and SLC3A2 and CD44 protein expression on LRC. The tumour hypoxia classification showed a significant impact only for small tumours. In multivariate analyses an independent correlation of tumour volume, SLC3A2 expression, and the 15-gene hypoxia signature with LRC was identified (CD44 protein n/a because of no event in the CD44-negative group). Logistic modelling showed that inclusion of CD44 protein expression and p16 overexpression significantly improved the performance to predict LRC at 2years compared to the model with tumour volume alone. - CONCLUSIONS: Tumour volume, HPV status, CSC marker expression and hypoxia gene signatures are potential prognostic biomarkers for patients with locally advanced HNSCC, who were treated by primary RCTx. The study also supports that the individual tumour volumes should generally be included in biomarker studies and that panels of biomarkers are superior to individual parameters. 
650 4 |a Adult 
650 4 |a Aged 
650 4 |a Biomarkers for radiotherapy 
650 4 |a Biomarkers, Tumor 
650 4 |a Cancer stem cells 
650 4 |a Carcinoma, Squamous Cell 
650 4 |a Cell Hypoxia 
650 4 |a Chemoradiotherapy 
650 4 |a Female 
650 4 |a Gene Expression Profiling 
650 4 |a Head and Neck Neoplasms 
650 4 |a HNSCC 
650 4 |a HPV 
650 4 |a Humans 
650 4 |a Hyaluronan Receptors 
650 4 |a Hypoxia 
650 4 |a Male 
650 4 |a Middle Aged 
650 4 |a Neoplastic Stem Cells 
650 4 |a Papillomaviridae 
650 4 |a Primary radiochemotherapy 
650 4 |a Prognosis 
650 4 |a Radiation Tolerance 
650 4 |a Retrospective Studies 
650 4 |a Squamous Cell Carcinoma of Head and Neck 
650 4 |a Tumor Burden 
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