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

Abstract

Simple SummaryThe 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.