title: Radiobiological investigation of dose-rate effects in intensity-modulated radiation therapy.
abstract: OBJECTIVE
  Intensity-modulated radiation therapy (IMRT) has proven extraordinary capability in physical terms such as target conformity, dose escalation in the target volume, and sparing of neighboring organs at risk. The radiobiological consequences of the protracted dose delivery for cell survival and cell cycle progression are still unclear and shall be examined in this study.
  
  
  METHODS
  Human lymphoblasts (TK6) and human melanoma cells (MeWo) were irradiated with protocols of increasing dose protraction. In addition, a new biophysical phantom was developed and used to transfer clinical IMRT plans to experimental cell irradiation. Clonogenic cell survival and cell cycle analysis were performed after various irradiation experiments.
  
  
  RESULTS
  In a first series of experiments, melanoma cells showed a highly significant increase of survival of 6.0% after protracted dose delivery of 2 Gy compared to conventional fast application with the same dose. Lymphoblastoid cells also showed a significant increase of survival of 2.2%. Experiments with patient plans in the phantom confirmed the trend of increased cell survival after protracted dose delivery. Cells were irradiated at 13 points in four different IMRT plans. In comparison to irradiation with application of the same dose in a classic four-field box, a significantly increased survival of 5.1% (mean value) was determined.
  
  
  CONCLUSIONS
  Even at fraction times of 15-30 min the protracted dose delivery increases the survival rates in cell culture. The altered survival rates indicate the importance of the dose rate in the effectivity of IMRT. Besides physical parameters the consideration of biological factors might contribute to the optimization of IMRT in the future.
authors.affiliation: Clinical Cooperation Unit Radiotherapy, German Cancer Research Center, Heidelberg, Germany. f.sterzing@dkfz.de
authors.forename: Florian
authors.initials: F
authors.lastname: Sterzing
authors.forename: Marc W
authors.initials: MW
authors.lastname: Münter
authors.forename: Mattias
authors.initials: M
authors.lastname: Schäfer
authors.forename: Peter
authors.initials: P
authors.lastname: Haering
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rhein
authors.forename: Christoph
authors.initials: C
authors.lastname: Thilmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D003470:Culture Media; D003627:Data Interpretation, Statistical; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D008545:Melanoma / Q000532:radiotherapy*; D019047:Phantoms, Imaging; D010865:Pilot Projects; D011853:Radiobiology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D012062:Relative Biological Effectiveness; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media