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)

被引：113

作者：

Linge, Annett ^{[1
,2
,10
,11
,12
,13
,14
]}

Lohaus, Fabian ^{[1
,2
,10
,11
,12
,13
,14
]}

Loeck, Steffen ^{[11
,12
,13
,14
]}

Nowak, Alexander ^{[11
,13
,14
,15
]}

Gudziol, Volker ^{[11
,14
,16
]}

Valentini, Chiara ^{[10
,11
,12
,13
,14
]}

von Neubeck, Claere ^{[1
,2
,11
,12
,13
]}

Juetz, Martin ^{[11
]}

Tinhofer, Inge ^{[1
,3
,17
]}

Budach, Volker ^{[1
,3
,17
]}

Sak, Ali ^{[1
,4
,18
]}

Stuschke, Martin ^{[1
,4
,18
]}

Balermpas, Panagiotis ^{[1
,5
,19
]}

Roedel, Claus ^{[1
,5
,19
]}

Grosu, Anca-Ligia ^{[1
,6
,20
]}

Abdollahi, Amir ^{[1
,7
,21
,22
,23
,24
]}

Debus, Juergen ^{[1
,7
,21
,22
,23
,25
]}

Ganswindt, Ute ^{[22
,26
,27
]}

Belka, Claus ^{[1
,22
,26
,27
]}

Pigorsch, Steffi ^{[1
,8
,28
]}

Combs, Stephanie E. ^{[1
,8
,28
,29
]}

Moennich, David ^{[1
,9
,30
,31
]}

Zips, Daniel ^{[1
,9
,30
,31
]}

Buchholz, Frank ^{[1
,2
,14
,32
]}

Aust, Daniela E. ^{[1
,2
,11
,14
,33
,34
]}

Baretton, Gustavo B. ^{[1
,2
,11
,14
,33
,34
]}

Thames, Howard D. ^{[35
]}

Dubrovska, Anna ^{[1
,2
,11
,12
,13
,37
]}

Alsner, Jan ^{[36
]}

Overgaard, Jens ^{[36
]}

Krause, Mechthild ^{[1
,2
,10
,11
,12
,13
,14
,37
]}

Baumann, Michael ^{[1
,2
,10
,11
,12
,13
,14
,37
]}

机构：

[1] German Canc Res Ctr, Heidelberg, Germany

[2] German Canc Consortium DKTK, Dresden, Germany

[3] German Canc Consortium DKTK, Berlin, Germany

[4] German Canc Consortium DKTK, Essen, Germany

[5] German Canc Consortium DKTK, Frankfurt, Germany

[6] German Canc Consortium DKTK, Freiburg, Germany

[7] German Canc Consortium DKTK, Heidelberg, Germany

[8] German Canc Consortium DKTK, Munich, Germany

[9] German Canc Consortium DKTK, Tubingen, Germany

[10] Tech Univ Dresden, Fac Med, Dept Radiat Oncol, Dresden, Germany

[11] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[12] Tech Univ Dresden, Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany

[13] Helmholtz Zentrum Dresden, Rossendorf, Germany

[14] Partner Site Dresden, Natl Ctr Tumor Dis NCT, Dresden, Germany

[15] Tech Univ Dresden, Fac Med, Dept Oral & Maxillofacial Surg, Dresden, Germany

[16] Tech Univ Dresden, Fac Med, Dept Otorhinolaryngol, Dresden, Germany

[17] Charite, Dept Radiooncol & Radiotherapy, Berlin, Germany

[18] Univ Duisburg Essen, Fac Med, Dept Radiotherapy, Duisburg, Germany

[19] Goethe Univ, Dept Radiotherapy & Oncol, Frankfurt, Germany

[20] Univ Freiburg, Dept Radiat Oncol, Freiburg, Germany

[21] Heidelberg Univ, Sch Med, Natl Ctr Radiat Res Oncol NCRO, HIRO, D-69115 Heidelberg, Germany

[22] Heidelberg Univ, Sch Med, Heidelberg Ion Therapy Ctr HIT, Dept Radiat Oncol, D-69115 Heidelberg, Germany

[23] Heidelberg Univ, Sch Med, Natl Ctr Tumor Dis NCT, D-69115 Heidelberg, Germany

[24] Heidelberg Univ, Sch Med, Translat Radiat Oncol, D-69115 Heidelberg, Germany

[25] Heidelberg Univ, Sch Med, Clin Cooperat Unit Radiat Oncol, D-69115 Heidelberg, Germany

[26] Ludwig Maximilians Univ Munchen, Dept Radiat Oncol, Munich, Germany

[27] Helmholtz Zentrum, Clin Cooperat Grp, Personalized Radiotherapy Head & Neck Canc, Munich, Germany

[28] Tech Univ Munich, Dept Radiat Oncol, D-80290 Munich, Germany

[29] Helmholtz Zentrum Munchen, Inst Innovat Radiotherapy iRT, Oberschleissheim, Germany

[30] Eberhard Karls Univ Tubingen, Fac Med, Dept Radiat Oncol, Tubingen, Germany

[31] Eberhard Karls Univ Tubingen, Univ Tubingen Hosp, Tubingen, Germany

[32] Tech Univ Dresden, Univ Hosp Carl Gustav Cams, UCC, Med Syst Biol, Dresden, Germany

[33] Tech Univ Dresden, Inst Pathol, Fac Med, Dresden, Germany

[34] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, UCC, Tumour & Normal Tissue Bank, Dresden, Germany

[35] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[36] Aarhus Univ Hosp, Dept Expt Clin Oncol, Aarhus, Denmark

[37] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol, Rossendorf, Germany

来源：

RADIOTHERAPY AND ONCOLOGY | 2016年 / 121卷 / 03期

关键词：

Cancer stem cells; HNSCC; HPV; Hypoxia; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; POSTOPERATIVE RADIOCHEMOTHERAPY; LOCOREGIONAL CONTROL; ADVANCED HEAD; LOCAL-CONTROL; RADIOTHERAPY; CARCINOMA; IMPACT; PREDICTS;

D O I：

10.1016/j.radonc.2016.11.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 2 years 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：364 / 373

页数：10

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