Anna Bandurska-Luque1, Steffen Löck2, Robert Haase3, Christian Richter4, Klaus Zöphel5, Nasreddin Abolmaali3, Annekatrin Seidlitz6, Steffen Appold6, Mechthild Krause7, Jörg Steinbach8, Jörg Kotzerke9, Daniel Zips10, Michael Baumann11, 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. Electronic address: anna.bandurska@uniklinikum-dresden.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 and German Cancer Research Center (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. 4. 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 and German Cancer Research Center (DKFZ), Heidelberg, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany. 5. 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, Technische Universität Dresden, Germany; National Center for Tumor Diseases, 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, Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Germany. 6. 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. 7. 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 and German Cancer Research Center (DKFZ), Heidelberg, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; National Center for Tumor Diseases, 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, Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. 8. Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden, Rossendorf, Institute of Radiopharmaceutical Cancer Research, Rossendorf, Germany. 9. Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 10. Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Germany. 11. 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 and German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases, 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, Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, 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 and German Cancer Research Center (DKFZ), Heidelberg, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; National Center for Tumor Diseases, 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, Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
Abstract
PURPOSE: This secondary analysis of the prospective study on repeat [18F]fluoromisonidazole (FMISO)-PET in patients with locally advanced head and neck squamous cell carcinomas (HNSCC) assessed the prognostic value of synchronous hypoxia in primary tumor (Tu) and lymph node metastases (LN), and evaluated whether the combined reading was of higher prognostic value than that of primary tumor hypoxia only. METHODS: This analysis included forty-five LN-positive HNSCC patients. FMISO-PET/CTs were performed at baseline, weeks 1, 2 and 5 of radiochemotherapy. Based on a binary scale, Tu and LN were categorized as hypoxic or normoxic, and two prognostic parameters were defined: Tu-hypoxia (independent of the LN oxygenation status) and synchronous Tu-and-LN-hypoxia. In fifteen patients with large LN (N = 21), additional quantitative analyses of FMISO-PET/CTs were performed. Imaging parameters at different time-points were correlated to the endpoints, i.e., locoregional control (LRC), local control (LC), regional control (RC) and time to progression (TTP). Survival curves were estimated using the cumulative incidence function. Univariable and multivariable Cox regression was used to evaluate the prognostic impact of hypoxia on the endpoints. RESULTS: Synchronous Tu-and-LN-hypoxia was a strong adverse prognostic factor for LC, LRC and TTP at any of the four time-points (p ≤ 0.004), whereas Tu-hypoxia only was significantly associated with poor LC and LRC in weeks 2 and 5 (p ≤ 0.047), and with TTP in week 1 (p = 0.046). The multivariable analysis confirmed the prognostic value of synchronous Tu-and-LN-hypoxia regarding LRC (HR = 14.8, p = 0.017). The quantitative FMISO-PET/CT parameters correlated with qualitative hypoxia scale and RC (p < 0.001, p ≤ 0.033 at week 2, respectively). CONCLUSIONS: This secondary analysis suggests that combined reading of primary tumor and LN hypoxia adds to the prognostic information of FMSIO-PET in comparison to primary tumor assessment alone in particular prior and early during radiochemotherapy. Confirmation in ongoing trials is needed before using this marker for personalized radiation oncology.
PURPOSE: This secondary analysis of the prospective study on repeat [18F]fluoromisonidazole (FMISO)-PET in patients with locally advanced head and neck squamous cell carcinomas (HNSCC) assessed the prognostic value of synchronous hypoxia in primary tumor (Tu) and lymph node metastases (LN), and evaluated whether the combined reading was of higher prognostic value than that of primary tumor hypoxia only. METHODS: This analysis included forty-five LN-positive HNSCC patients. FMISO-PET/CTs were performed at baseline, weeks 1, 2 and 5 of radiochemotherapy. Based on a binary scale, Tu and LN were categorized as hypoxic or normoxic, and two prognostic parameters were defined: Tu-hypoxia (independent of the LN oxygenation status) and synchronous Tu-and-LN-hypoxia. In fifteen patients with large LN (N = 21), additional quantitative analyses of FMISO-PET/CTs were performed. Imaging parameters at different time-points were correlated to the endpoints, i.e., locoregional control (LRC), local control (LC), regional control (RC) and time to progression (TTP). Survival curves were estimated using the cumulative incidence function. Univariable and multivariable Cox regression was used to evaluate the prognostic impact of hypoxia on the endpoints. RESULTS: Synchronous Tu-and-LN-hypoxia was a strong adverse prognostic factor for LC, LRC and TTP at any of the four time-points (p ≤ 0.004), whereas Tu-hypoxia only was significantly associated with poor LC and LRC in weeks 2 and 5 (p ≤ 0.047), and with TTP in week 1 (p = 0.046). The multivariable analysis confirmed the prognostic value of synchronous Tu-and-LN-hypoxia regarding LRC (HR = 14.8, p = 0.017). The quantitative FMISO-PET/CT parameters correlated with qualitative hypoxia scale and RC (p < 0.001, p ≤ 0.033 at week 2, respectively). CONCLUSIONS: This secondary analysis suggests that combined reading of primary tumor and LN hypoxia adds to the prognostic information of FMSIO-PET in comparison to primary tumor assessment alone in particular prior and early during radiochemotherapy. Confirmation in ongoing trials is needed before using this marker for personalized radiation oncology.
Authors: Daniela Thorwarth; Stefan Welz; David Mönnich; Christina Pfannenberg; Konstantin Nikolaou; Matthias Reimold; Christian La Fougère; Gerald Reischl; Paul-Stefan Mauz; Frank Paulsen; Markus Alber; Claus Belka; Daniel Zips Journal: J Nucl Med Date: 2019-05-10 Impact factor: 10.057
Authors: Anna Bandurska-Luque; Steffen Löck; Robert Haase; Christian Richter; Klaus Zöphel; Rosalind Perrin; Steffen Appold; Mechthild Krause; Jörg Steinbach; Jörg Kotzerke; Frank Hofheinz; Daniel Zips; Michael Baumann; Esther G C Troost Journal: Clin Transl Radiat Oncol Date: 2019-02-15
Authors: Sebastian Sanduleanu; Olga Hamming-Vrieze; Frederik W R Wesseling; Aniek J G Even; Frank J Hoebers; Ann Hoeben; Wouter V Vogel; Margot E T Tesselaar; Daniel Parvin; Harry Bartelink; Philippe Lambin Journal: Clin Transl Radiat Oncol Date: 2020-04-18
Authors: Ramesh Paudyal; Milan Grkovski; Jung Hun Oh; Heiko Schöder; David Aramburu Nunez; Vaios Hatzoglou; Joseph O Deasy; John L Humm; Nancy Y Lee; Amita Shukla-Dave Journal: Cancers (Basel) Date: 2021-08-03 Impact factor: 6.639