Sebastian Zschaeck1, Steffen Löck2, Frank Hofheinz3, Daniel Zips4, Lise Saksø Mortensen5, Klaus Zöphel6, Esther G C Troost7, Simon Boeke8, Mette Saksø5, David Mönnich8, Annekatrin Seidlitz9, Jørgen Johansen10, Tomas Skripcak11, Vincent Gregoire12, Jens Overgaard5, Michael Baumann13, Mechthild Krause7. 1. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, 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; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiation Oncology, Germany; Berlin Institute of Health (BIH), Germany. Electronic address: Sebastian.Zschaeck@charite.de. 2. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Biostatistics and Modeling in Radiation Oncology Group, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum, Dresden - Rossendorf, Germany. 3. Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Germany. 4. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Germany; German Cancer Consortium (DKTK), partner site Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 5. Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. 6. German Cancer Consortium (DKTK), partner site Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, 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 Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany. 7. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, 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; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, 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, Germany; Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Germany. 8. Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Germany. 9. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, 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. 10. Department of Oncology, Odense University Hospital (OUH), Denmark. 11. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 12. St. Luc University Hospital, Brussels, Belgium. 13. 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 Tu¨bingen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, 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; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract
BACKGROUND AND PURPOSE: Tumor hypoxia plays an important role in head and neck squamous cell carcinomas (HNSCC). Various positron emission tomography (PET) tracers promise non-invasive assessment of tumor hypoxia. So far, the applicability of hypoxia PET is hampered by monocentric imaging trials with few patients. MATERIALS AND METHODS: Multicenter individual patient data based meta-analysis of the original PET data from four prospective imaging trials was performed. All patients had localized disease and were treated with curatively intended radio(-chemo)therapy. Hypoxia PET imaging was performed with 18F-Fluoromisonidazole (FMISO, 102 patients) or 18F-Fluoroazomycin-arabinoside (FAZA, 51 patients). Impact of hypoxia PET parameters on loco-regional control (LRC) and overall survival (OS) was analyzed by uni- and multivariable Cox regression. RESULTS: Baseline characteristics between participating centers differed significantly, especially regarding T stage (p < 0.001), tumor volume (p < 0.001) and p16 status (p = 0.009). The commonly used hypoxia parameters, maximal tumor-to-muscle ratio (TMRmax) and hypoxic volume with 1.6 threshold (HV1.6), showed a strong association with LRC (p = 0.001) and OS (p < 0.001). These findings were irrespective of the radiotracer and the same cut-off values could be applied for FMISO and FAZA (TMRmax > 2.0 or HV1.6 > 1.5 ml). The effect size of TMRmax was similar for subgroups of patients defined by radiotracer, p16 status and FDG-PET parameters for LRC and OS, respectively. CONCLUSION: PET measured hypoxia is robust and has a strong impact on LRC and OS in HNSCC. The most commonly investigated tracers FMISO and FAZA can probably be used equivalently in multicenter trials. Optimal strategies to improve the dismal outcome of hypoxic tumors remain elusive.
BACKGROUND AND PURPOSE:Tumor hypoxia plays an important role in head and neck squamous cell carcinomas (HNSCC). Various positron emission tomography (PET) tracers promise non-invasive assessment of tumor hypoxia. So far, the applicability of hypoxia PET is hampered by monocentric imaging trials with few patients. MATERIALS AND METHODS: Multicenter individual patient data based meta-analysis of the original PET data from four prospective imaging trials was performed. All patients had localized disease and were treated with curatively intended radio(-chemo)therapy. Hypoxia PET imaging was performed with 18F-Fluoromisonidazole (FMISO, 102 patients) or 18F-Fluoroazomycin-arabinoside (FAZA, 51 patients). Impact of hypoxia PET parameters on loco-regional control (LRC) and overall survival (OS) was analyzed by uni- and multivariable Cox regression. RESULTS: Baseline characteristics between participating centers differed significantly, especially regarding T stage (p < 0.001), tumor volume (p < 0.001) and p16 status (p = 0.009). The commonly used hypoxia parameters, maximal tumor-to-muscle ratio (TMRmax) and hypoxic volume with 1.6 threshold (HV1.6), showed a strong association with LRC (p = 0.001) and OS (p < 0.001). These findings were irrespective of the radiotracer and the same cut-off values could be applied for FMISO and FAZA (TMRmax > 2.0 or HV1.6 > 1.5 ml). The effect size of TMRmax was similar for subgroups of patients defined by radiotracer, p16 status and FDG-PET parameters for LRC and OS, respectively. CONCLUSION: PET measured hypoxia is robust and has a strong impact on LRC and OS in HNSCC. The most commonly investigated tracers FMISO and FAZA can probably be used equivalently in multicenter trials. Optimal strategies to improve the dismal outcome of hypoxic tumors remain elusive.
Authors: Gabriel Adrian; Henrik Carlsson; Elisabeth Kjellén; Johanna Sjövall; Björn Zackrisson; Per Nilsson; Maria Gebre-Medhin Journal: Radiat Oncol Date: 2022-06-14 Impact factor: 4.309
Authors: Alexander Rühle; Anca-L Grosu; Nicole Wiedenmann; Juri Ruf; Birgit Bieber; Raluca Stoian; Andreas R Thomsen; Eleni Gkika; Peter Vaupel; Dimos Baltas; Wolfgang A Weber; Michael Mix; Nils H Nicolay Journal: Clin Transl Radiat Oncol Date: 2022-02-21
Authors: Martin Dolezel; Marek Slavik; Tomas Blazek; Tomas Kazda; Pavel Koranda; Lucia Veverkova; Petr Burkon; Jakub Cvek Journal: J Pers Med Date: 2022-07-29
Authors: Constantin Lapa; Ursula Nestle; Nathalie L Albert; Christian Baues; Ambros Beer; Andreas Buck; Volker Budach; Rebecca Bütof; Stephanie E Combs; Thorsten Derlin; Matthias Eiber; Wolfgang P Fendler; Christian Furth; Cihan Gani; Eleni Gkika; Anca-L Grosu; Christoph Henkenberens; Harun Ilhan; Steffen Löck; Simone Marnitz-Schulze; Matthias Miederer; Michael Mix; Nils H Nicolay; Maximilian Niyazi; Christoph Pöttgen; Claus M Rödel; Imke Schatka; Sarah M Schwarzenboeck; Andrei S Todica; Wolfgang Weber; Simone Wegen; Thomas Wiegel; Constantinos Zamboglou; Daniel Zips; Klaus Zöphel; Sebastian Zschaeck; Daniela Thorwarth; Esther G C Troost Journal: Strahlenther Onkol Date: 2021-07-14 Impact factor: 3.621