Steffen Löck1, Annett Linge2, Annekatrin Seidlitz3, Anna Bandurska-Luque3, Alexander Nowak4, Volker Gudziol5, Frank Buchholz6, Daniela E Aust7, Gustavo B Baretton7, Klaus Zöphel8, Jörg Steinbach9, Jörg Kotzerke8, Jens Overgaard10, Daniel Zips11, Mechthild Krause12, Michael Baumann12, Esther G C Troost12. 1. 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 Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. Electronic address: steffen.loeck@oncoray.de. 2. 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 Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. 3. 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. 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 Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität 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 Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 6. 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; University Cancer Center (UCC), Medical Systems Biology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 7. 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 Center (UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 8. 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 Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 9. 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 Radiopharmaceutical Cancer Research, Germany. 10. Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. 11. Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Germany. 12. 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 Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, 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, Germany.
Abstract
BACKGROUND: Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [18F]fluoromisonidazole (FMISO)-PET/CT imaging with hypoxia-associated gene expressions on a cohort of 50 head and neck squamous cell carcinoma (HNSCC) patients and compare their prognostic value for response to radiochemotherapy (RCTx). METHODS: FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression. RESULTS: The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers. CONCLUSION: We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.
BACKGROUND:Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [18F]fluoromisonidazole (FMISO)-PET/CT imaging with hypoxia-associated gene expressions on a cohort of 50 head and neck squamous cell carcinoma (HNSCC) patients and compare their prognostic value for response to radiochemotherapy (RCTx). METHODS:FMISO-PET/CT images of 50 HNSCCpatients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression. RESULTS: The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers. CONCLUSION: We observed low correlations between hypoxiaFMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.
Authors: Jairo A Socarrás Fernández; David Mönnich; Sara Leibfarth; Stefan Welz; Alex Zwanenburg; Stefan Leger; Steffen Löck; Christina Pfannenberg; Christian La Fougère; Gerald Reischl; Michael Baumann; Daniel Zips; Daniela Thorwarth Journal: Phys Imaging Radiat Oncol Date: 2020-07
Authors: Patrick N Song; Ameer Mansur; Yun Lu; Deborah Della Manna; Andrew Burns; Sharon Samuel; Katherine Heinzman; Suzanne E Lapi; Eddy S Yang; Anna G Sorace Journal: Cancers (Basel) Date: 2022-02-17 Impact factor: 6.639
Authors: Alexander Rühle; Nicole Wiedenmann; Jamina T Fennell; Michael Mix; Juri Ruf; Raluca Stoian; Andreas R Thomsen; Peter Vaupel; Dimos Baltas; Anca-L Grosu; Nils H Nicolay Journal: Eur J Nucl Med Mol Imaging Date: 2021-11-13 Impact factor: 10.057
Authors: Ruth J Muschel; Bostjan Markelc; Jakob R Kaeppler; Jianzhou Chen; Mario Buono; Jenny Vermeer; Pavitra Kannan; Wei-Chen Cheng; Dimitrios Voukantsis; James M Thompson; Mark A Hill; Danny Allen; Ana Gomes; Veerle Kersemans; Paul Kinchesh; Sean Smart; Francesca Buffa; Claus Nerlov Journal: EMBO Rep Date: 2022-07-18 Impact factor: 9.071
Authors: Asier Rabasco Meneghetti; Alex Zwanenburg; Annett Linge; Fabian Lohaus; Marianne Grosser; Gustavo B Baretton; Goda Kalinauskaite; Ingeborg Tinhofer; Maja Guberina; Martin Stuschke; Panagiotis Balermpas; Jens von der Grün; Ute Ganswindt; Claus Belka; Jan C Peeken; Stephanie E Combs; Simon Böke; Daniel Zips; Esther G C Troost; Mechthild Krause; Michael Baumann; Steffen Löck Journal: Sci Rep Date: 2022-10-06 Impact factor: 4.996