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Patil, S.* ; Linge, A.* ; Hiepe, H.* ; Grosser, M.* ; Lohaus, F.* ; Gudziol, V.* ; Kemper, M.* ; Nowak, A.* ; Haim, D.* ; Tinhofer, I.* ; Budach, V.* ; Guberina, M.* ; Stuschke, M.* ; Balermpas, P.* ; Grün, J.V.* ; Schäfer, H.* ; Grosu, A.L.* ; Ganswindt, U.* ; Belka, C. ; Pigorsch, S.* ; Combs, S.E. ; Boeke, S.* ; Zips, D.* ; Jöhrens, K.* ; Baretton, G.B.* ; Baumann, M.* ; Löck, S.*

A novel 2-metagene signature to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and are treated with PORT.

Cancers 14:3031 (2022)

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(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.

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