title: High dose rate and flattening filter free irradiation can be safely implemented in clinical practice.
abstract: OBJECTIVE
  We hypothesize that flattening filter free (FFF) high dose rate irradiation will decrease cell survival in normal and cancer cells with more pronounced effects in DNA repair deficient cells. Additionally, we hypothesize that removal of the flattening filter will result in an enhanced relative biological effectiveness independent of the dose rate.
  
  
  METHODS
  Clonogenic survival was assessed after exposure to dose rates of 4 or 24 Gy/min (FFF 10 megavolt [MV] photon beam) using a Varian TrueBeam accelerator. Additionally, cells were exposed to 4 Gy/min with or without flattening filter. Relative biological effectiveness estimations were performed comparing the different beam photon spectra.
  
  
  RESULTS
  Cell survival in tumor and normal cell lines was not influenced by high dose rate irradiation. The intrinsic radiation sensitivity of DNA repair deficient cells was not affected by high dose rate compared to normal dose rate. Furthermore, the relative biological effectiveness was not significantly different from unity in any of the cell lines for both FFF and conventional flattened beam exposures.
  
  
  CONCLUSIONS
  High dose rate irradiation did not affect long-term survival and DNA repair for cell lines of different tissues. This suggests that high dose rate does not influence treatment outcome or treatment toxicity and could be safely implemented in clinical routine.
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Dubois
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Rianne
authors.initials: R
authors.lastname: Biemans
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Reniers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Bosmans
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Daniela
authors.initials: D
authors.lastname: Trani
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Podesta
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kollaard
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Kasper M A
authors.initials: KM
authors.lastname: Rouschop
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Theys
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Vooijs
authors.affiliation: b Department of Radiation Oncology , University Hospital Zurich , Zurich , Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Pruschy
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Verhaegen
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , the Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells / Q000166:cytology / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D059765:Homologous Recombination / Q000528:radiation effects; D006801:Humans; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D012449:Safety
keywords: DNA repair; High dose rate irradiation; cell survival; flattening filter free (FFF)