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Development and validation of a gene signature for patients with head and neck carcinomas treated by postoperative radio(chemo)therapy

Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperativ...

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Main Authors: Schmidt, Stefan (Author) , Linge, Annett (Author) , Zwanenburg, Alex (Author) , Leger, Stefan (Author) , Lohaus, Fabian (Author) , Krenn, Constanze (Author) , Appold, Steffen (Author) , Gudziol, Volker (Author) , Nowak, Alexander (Author) , Neubeck, Cläre von (Author) , Tinhofer, Inge (Author) , Budach, Volker (Author) , Sak, Ali (Author) , Stuschke, Martin (Author) , Balermpas, Panagiotis (Author) , Rödel, Claus (Author) , Bunea, Hatice (Author) , Grosu, Anca-Ligia (Author) , Abdollahi, Amir (Author) , Debus, Jürgen (Author) , Ganswindt, Ute (Author) , Belka, Claus (Author) , Pigorsch, Steffi (Author) , Combs, Stephanie (Author) , Mönnich, David (Author) , Zips, Daniel (Author) , Baretton, Gustavo Bruno (Author) , Buchholz, Frank (Author) , Baumann, Michael (Author) , Krause, Mechthild (Author) , Löck, Steffen (Author)
Format: Article (Journal)
Language:English
Published: 2018 Mar 15
In: Clinical cancer research
Year: 2018, Volume: 24, Issue: 6, Pages: 1364-1374
ISSN:1557-3265
DOI:https://doi.org/10.1158/1078-0432.CCR-17-2345
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1158/1078-0432.CCR-17-2345
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Author Notes:Stefan Schmidt, Annett Linge, Alex Zwanenburg, Stefan Leger, Fabian Lohaus, Constanze Krenn, Steffen Appold, Volker Gudziol, Alexander Nowak, Cläre von Neubeck, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Hatice Bunea, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Gustavo B. Baretton, Frank Buchholz, Michael Baumann, Mechthild Krause and Steffen Löck for the DKTK-ROG
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Summary:Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C).Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms.Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1 The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P < 0.001).Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364-74. ©2018 AACR.
Item Description:Gesehen am 31.03.2020
Physical Description:Online Resource
ISSN:1557-3265
DOI:https://doi.org/10.1158/1078-0432.CCR-17-2345

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