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Dokumenttyp:
Journal Article
Autor(en):
Schmidt, Stefan; Linge, Annett; Zwanenburg, Alex; Leger, Stefan; Lohaus, Fabian; Krenn, Constanze; Appold, Steffen; Gudziol, Volker; Nowak, Alexander; von Neubeck, Cläre; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Baumann, Michael; Krause, Mech...     »
Titel:
Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy.
Abstract:
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.
Zeitschriftentitel:
Clin Cancer Res
Jahr:
2018
Band / Volume:
24
Heft / Issue:
6
Seitenangaben Beitrag:
1364-1374
Sprache:
eng
Volltext / DOI:
doi:10.1158/1078-0432.CCR-17-2345
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/29298797
Print-ISSN:
1078-0432
TUM Einrichtung:
Klinik und Poliklinik für RadioOnkologie und Strahlentherapie
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