Biomarker signatures for primary radiochemotherapy of locally advanced HNSCC - Hypothesis generation on a multicentre cohort of the DKTK-ROG

Steffen Löck; Annett Linge; Fabian Lohaus; Nadja Ebert; Volker Gudziol; Alexander Nowak; Ingeborg Tinhofer; Goda Kalinauskaite; Maja Guberina; Martin Stuschke; Panagiotis Balermpas; Jens von der Grün; Anca-Ligia Grosu; Jürgen Debus; Ute Ganswindt; Claus Belka; Jan C Peeken; Stephanie E Combs; Chiara De-Colle; Daniel Zips; Gustavo B Baretton; Mechthild Krause; Michael Baumann; DKTK-ROG

doi:10.1016/j.radonc.2022.02.009

Biomarker signatures for primary radiochemotherapy of locally advanced HNSCC - Hypothesis generation on a multicentre cohort of the DKTK-ROG

Radiother Oncol. 2022 Apr:169:8-14. doi: 10.1016/j.radonc.2022.02.009. Epub 2022 Feb 16.

Authors

Steffen Löck¹, Annett Linge², Fabian Lohaus², Nadja Ebert³, Volker Gudziol⁴, Alexander Nowak⁵, Ingeborg Tinhofer⁶, Goda Kalinauskaite⁶, Maja Guberina⁷, Martin Stuschke⁷, Panagiotis Balermpas⁸, Jens von der Grün⁸, Anca-Ligia Grosu⁹, Jürgen Debus¹⁰, Ute Ganswindt¹¹, Claus Belka¹², Jan C Peeken¹³, Stephanie E Combs¹³, Chiara De-Colle¹⁴, Daniel Zips¹⁴, Gustavo B Baretton¹⁵, Mechthild Krause¹⁶, Michael Baumann¹⁷; DKTK-ROG

Affiliations

¹ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: steffen.loeck@oncoray.de.
² German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
³ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴ National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Department of Otorhinolaryngology, Head and Neck Surgery, Municipal Hospital Dresden, Germany.
⁵ National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
⁶ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiooncology and Radiotherapy, Berlin, Germany.
⁷ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen, Germany; Department of Radiation Therapy, University Hospital, Medical Faculty, University of Duisburg-Essen, Germany.
⁸ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Frankfurt, Germany; Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
⁹ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Freiburg, Germany; Department of Radiation Oncology, Medical Center, Medical Faculty, University of Freiburg, Germany.
¹⁰ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; Heidelberg Ion Therapy Center (HIT), Department of Radiation Oncology, University of Heidelberg Medical School, Germany; National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany.
¹¹ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Munich, Germany; Department of Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany; Clinical Cooperation Group, Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum, Munich, Germany; Department of Radiation Oncology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.
¹² German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Munich, Germany; Department of Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany; Clinical Cooperation Group, Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum, Munich, Germany.
¹³ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Munich, Germany; Department of Radiation Oncology, Technische Universität München, Munich, Germany; Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany.
¹⁴ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Tübingen, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Germany.
¹⁵ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Tumour- and Normal Tissue Bank, University Cancer Centre (UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁶ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany.
¹⁷ German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.

PMID: 35182686
DOI: 10.1016/j.radonc.2022.02.009

Abstract

Purpose: To develop prognostic biomarker signatures for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on previously published molecular analyses of the retrospective biomarker study of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG).

Material and methods: In previous studies on the retrospective DKTK-ROG HNSCC cohort treated with primary RCTx, the following clinical parameters and biomarkers were evaluated and found to be significantly associated with loco-regional tumour control (LRC) or overall survival (OS): tumour volume, p16 status, expression of cancer stem cell markers CD44 and SLC3A2, expressions of hypoxia-associated gene signatures, tumour mutational burden (TMB), single nucleotide polymorphisms (SNPs) in the ERCC2 gene (rs1799793, rs13181) and ERCC5 gene (rs17655) as well as the expression of CXCR4, SDF-1 and CD8. These biomarkers were combined in multivariable modelling using Cox-regression with backward variable selection.

Results: A baseline signature containing the widely accepted parameters tumour volume, p16 status, cancer stem cell marker expression (CD44), and hypoxia-associated gene expression has been defined, representing the main hypothesis of the study. Furthermore, the baseline signature was extended by additional prognostic biomarkers and a data-driven signature without any pre-hypothesis was generated for both endpoints. In these signatures, the SNPs rs1799793 and rs17655 as well as CXCR4, SDF-1 and SLC3A2 expression were additionally included. The signatures showed significant patient stratifications for LRC and OS.

Conclusion: Three biomarker signatures were defined for patients with locally advanced HNSCC treated with primary RCTx for the endpoints LRC and OS. These signatures will be validated in the prospective HNprädBio study of the DKTK-ROG that recently completed recruitment, before potential application in an interventional trial.

Keywords: Biomarkers; HNSCC; Primary radiochemotherapy; Signature; Validation.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Chemoradiotherapy
Head and Neck Neoplasms* / genetics
Head and Neck Neoplasms* / therapy
Humans
Hypoxia
Prognosis
Prospective Studies
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / therapy
Xeroderma Pigmentosum Group D Protein

Substances

Biomarkers, Tumor
Xeroderma Pigmentosum Group D Protein
ERCC2 protein, human