title: Kill-painting of hypoxic tumours in charged particle therapy.
abstract: Solid tumours often present regions with severe oxygen deprivation (hypoxia), which are resistant to both chemotherapy and radiotherapy. Increased radiosensitivity as a function of the oxygen concentration is well described for X-rays. It has also been demonstrated that radioresistance in anoxia is reduced using high-LET radiation rather than conventional X-rays. However, the dependence of the oxygen enhancement ratio (OER) on radiation quality in the regions of intermediate oxygen concentrations, those normally found in tumours, had never been measured and biophysical models were based on extrapolations. Here we present a complete survival dataset of mammalian cells exposed to different ions in oxygen concentration ranging from normoxia (21%) to anoxia (0%). The data were used to generate a model of the dependence of the OER on oxygen concentration and particle energy. The model was implemented in the ion beam treatment planning system to prescribe uniform cell killing across volumes with heterogeneous radiosensitivity. The adaptive treatment plans have been validated in two different accelerator facilities, using a biological phantom where cells can be irradiated simultaneously at three different oxygen concentrations. We thus realized a hypoxia-adapted treatment plan, which will be used for painting by voxel of hypoxic tumours visualized by functional imaging.
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.|Research Center for Charged Particle Therapy and International Open Laboratory, National Institute of Radiological Sciences, 263-8555 Chiba, Japan.
authors.forename: Walter
authors.initials: W
authors.lastname: Tinganelli
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.|Technical University Darmstadt, 64283 Darmstadt, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.affiliation: Research Center for Charged Particle Therapy and International Open Laboratory, National Institute of Radiological Sciences, 263-8555 Chiba, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hirayama
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Krämer
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maier
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.
authors.forename: Wilma
authors.initials: W
authors.lastname: Kraft-Weyrather
authors.affiliation: Research Center for Charged Particle Therapy and International Open Laboratory, National Institute of Radiological Sciences, 263-8555 Chiba, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Scifoni
mesh_terms: D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D010100:Oxygen / Q000502:physiology; D011836:Radiation Tolerance; D011880:Radiotherapy Planning, Computer-Assisted; D061089:Radiotherapy, Image-Guided
chemical_list: D010100:Oxygen