Christina Schütze1, Ralf Bergmann2, Kerstin Brüchner3, Birgit Mosch4, Ala Yaromina5, Daniel Zips6, Franziska Hessel7, Mechthild Krause1, Howard Thames8, Jörg Kotzerke9, Jörg Steinbach10, Michael Baumann11, Bettina Beuthien-Baumann12. 1. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. 2. PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany. 3. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden-Rossendorf, Germany. 4. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany. 5. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology (MAASTRO Lab), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 6. Department of Radiation Oncology, Eberhard Karls University Tübingen, Germany; German Cancer Consortium (DKTK), Site Tübingen, Germany. 7. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 8. University of Texas, M.D. Anderson Cancer Centre, Department of Biostatistics and Applied Mathematics, Houston, United States. 9. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK), Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. 10. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK), Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. 11. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK), Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. 12. OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany. Electronic address: b.beuthien@hzdr.de.
Abstract
OBJECTIVE: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [(18)F]fluoromisonidazole ([(18)F]FMISO) PET. MATERIALS AND METHODS: FaDu human squamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [(18)F]FMISO PET before irradiation with single doses of 25 or 35Gy under normal blood flow conditions. [(18)F]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120days after irradiation. The endpoints were permanent local tumour control and time to local recurrence. RESULTS: HV varied between 38 and 291mm(3) (median 105mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p=0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR=0.82 [95% CI 0.71; 0.93], p=0.002 and HR=0.86 [0.78; 0.95], p=0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level. CONCLUSIONS: The negative effect of [(18)F]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [(18)F]FMISO HV. Making the assumption that variable [(18)F]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [(18)F]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules.
OBJECTIVE: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [(18)F]fluoromisonidazole ([(18)F]FMISO) PET. MATERIALS AND METHODS: FaDu humansquamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [(18)F]FMISO PET before irradiation with single doses of 25 or 35Gy under normal blood flow conditions. [(18)F]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120days after irradiation. The endpoints were permanent local tumour control and time to local recurrence. RESULTS: HV varied between 38 and 291mm(3) (median 105mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p=0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR=0.82 [95% CI 0.71; 0.93], p=0.002 and HR=0.86 [0.78; 0.95], p=0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level. CONCLUSIONS: The negative effect of [(18)F]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [(18)F]FMISO HV. Making the assumption that variable [(18)F]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [(18)F]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules.
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: Derek A White; Zhang Zhang; Li Li; Jeni Gerberich; Strahinja Stojadinovic; Peter Peschke; Ralph P Mason Journal: Cancer Lett Date: 2016-06-03 Impact factor: 8.679
Authors: Nicole Wiedenmann; Hatice Bunea; Hans C Rischke; Andrei Bunea; Liette Majerus; Lars Bielak; Alexey Protopopov; Ute Ludwig; Martin Büchert; Christian Stoykow; Nils H Nicolay; Wolfgang A Weber; Michael Mix; Philipp T Meyer; Jürgen Hennig; Michael Bock; Anca L Grosu Journal: Radiat Oncol Date: 2018-08-29 Impact factor: 3.481