A Novel 2-Metagene Signature to Identify High-Risk HNSCC Patients amongst Those Who Are Clinically at Intermediate Risk and Are Treated with PORT

Patil, Shivaprasad; Linge, Annett; Hiepe, Hannah; Grosser, Marianne; Lohaus, Fabian; Gudziol, Volker; Kemper, Max; Nowak, Alexander; Haim, Dominik; Tinhofer, Inge; Budach, Volker; Guberina, Maja; Stuschke, Martin; Balermpas, Panagiotis; Grun, Jens von der; Schafer, Henning; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E.; Boeke, Simon; Zips, Daniel; Johrens, Korinna; Baretton, Gustavo B.; Baumann, Michael; Krause, Mechthild und Lock, Steffen (2022): A Novel 2-Metagene Signature to Identify High-Risk HNSCC Patients amongst Those Who Are Clinically at Intermediate Risk and Are Treated with PORT. In: Cancers, Bd. 14, Nr. 12, 3031

Abstract

Simple Summary The aim of this matched-pair study including patients with locally advanced head and neck squamous cell carcinoma (HNSCC) was to identify patients who are biologically at high risk for the development of loco-regional recurrences after surgery and postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors, with the help of a novel predictive gene signature. These patients may benefit from treatment with postoperative radiochemotherapy (PORT-C). Based on 108 matched patient pairs treated with PORT and PORT-C, we identified a gene signature consisting of two metagenes. A significant association of the interaction between the risk classification by this signature and the type of treatment was observed for the endpoint loco-regional control (LRC), i.e., the 2-metagene signature was indicative for the type of treatment. The developed signature may thus help to identify high-risk patients currently treated with PORT, who may benefit from additional concurrent chemotherapy. (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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch