TY  - JOUR
A1  - Patil, Shivaprasad
A1  - Linge, Annett
A1  - Hiepe, Hannah
A1  - Grosser, Marianne
A1  - Lohaus, Fabian
A1  - Gudziol, Volker
A1  - Kemper, Max
A1  - Nowak, Alexander
A1  - Haim, Dominik
A1  - Tinhofer, Ingeborg
A1  - Budach, Volker
A1  - Guberina, Maja
A1  - Stuschke, Martin
A1  - Balermpas, Panagiotis
A1  - Müller-von der Grün, Jens
A1  - Schäfer, Henning Sebastian
A1  - Grosu, Anca-Ligia
A1  - Abdollahi, Amir
A1  - Debus, Jürgen
A1  - Ganswindt, Ute
A1  - Belka, Claus
A1  - Pigorsch, Steffi Ulrike
A1  - Combs, Stephanie
A1  - Böke, Simon
A1  - Zips, Daniel
A1  - Jöhrens, Korinna
A1  - Baretton, Gustavo Bruno
A1  - Baumann, Michael
A1  - Krause, Mechthild
A1  - Löck, Steffen
T1  - A novel 2-metagene signature to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and are treated with PORT
T2  - Cancers
N2  - (1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.
KW  - head and neck squamous cell carcinoma
KW  - gene signature
KW  - postoperative radiotherapy
KW  - postoperative radiochemotherapy
KW  - propensity score matching
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/70918
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-709183
SN  - 2072-6694
N1  - The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14123031/s1, Figure S1: Loco–regional tumour control (A), overall survival (B) and freedom from distant metastases (C) on the PORT and PORT-C cohort before propensity score matching; Figure S2: Loco–regional tumour control (A), overall survival (B) and freedom from distant metastases (C) on the PORT and PORT-C cohort after propensity score matching; Figure S3: Patient stratification by the 2-metagene signature for overall survival (OS) in the PORT (A) and the PORT-C cohort (B) and for freedom from distant metastases (DM) in the PORT (C) and the PORT-C cohort (D); Table S1: Univariable Cox regression of loco–regional tumour control for the clinical parameters in the PORT and PORT-C cohorts before propensity score matching.; Table S2: Patient characteristics for the PORT and PORT-C cohorts before propensity score matching; Table S3: Comparison of the clinical parameters between PORT and PORT-C patients in the original sample and in the propensity score matched sample. The standardized mean and the standardized mean difference between the cohorts are shown. Table S4: Multivariable Cox regression of overall survival for the 2-metagene signature and their interaction term with treatment type; Table S5: Multivariable Cox regression of freedom from distant metastases for the 2-metagene signature and their interaction term with treatment type.
N1  - The study was partly funded by the German Cancer Consortium (DKTK). The DKTK is funded as one of the National German Health Centres by the Federal German Ministry of Education and Research (BMBF).
VL  - 14
IS  - 12, art.  303
SP  - 1
EP  - 13
PB  - MDPI
CY  - Basel
ER  -