title: Impact of flattening-filter-free radiation on the clonogenic survival of astrocytic cell lines.
abstract: OBJECTIVE
  Flattening-filter-free (FFF) beams are increasingly used in radiotherapy as delivery times can be substantially reduced. However, the relative biologic effectiveness (RBE) of FFF may be increased relative to conventional flattened (FLAT) beams due to differences in energy spectra. Therefore, we investigated the effects of FFF and FLAT beams on the clonogenic survival of astrocytoma cells.
  
  
  METHODS
  Three cell lines (U251, U251-MGMT, and U87) were irradiated with 6-MV and 10-MV X-rays from a linear accelerator in FFF- or FLAT-beam modes at dose rates in the range of 0.5-24 Gy/min. The surviving fraction (SF) as function of dose (2-12 Gy) was determined by the colony formation assay and fitted by the linear-quadratic model. For both beams (FFF or FLAT), the cells were pelleted in conical 15-ml centrifuge tubes and irradiated at 2-cm depth in a 1 × 1-cm(2) area on the central axis of a 30 × 30-cm(2) field. Dosimetry was performed with a 0.3-cm(3) rigid ionization chamber. RBE was determined for FFF versus FLAT irradiation.
  
  
  RESULTS
  The RBE of FFF at 7.3-11.3 Gy was 1.027 ± 0.013 and 1.063 ± 0.018 relative to FLAT beams for 6- and 10-MV beams, respectively, and was only significantly higher than 1 for 10 MV. Significantly increased survival rates were seen for lower dose rates (0.5 Gy/min FLAT vs. 5 Gy/min FLAT) at higher doses (11.9 Gy), while no differences were seen at dose rates  ≥ 1.4 Gy/min (1.4 Gy/min FFF vs. 14 Gy/min FFF and 2.4 Gy/min FFF vs. 24 Gy/min FFF).
  
  
  CONCLUSIONS
  FFF beams showed only a slightly increased RBE relative to FLAT beams in this experimental set-up, which is unlikely to result in clinically relevant differences in outcome.
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Steenken
authors.forename: Jens
authors.initials: J
authors.lastname: Fleckenstein
authors.forename: Stefan
authors.initials: S
authors.lastname: Kegel
authors.forename: Lennart
authors.initials: L
authors.lastname: Jahnke
authors.forename: Anna
authors.initials: A
authors.lastname: Simeonova
authors.forename: Linda
authors.initials: L
authors.lastname: Hartmann
authors.forename: Jens
authors.initials: J
authors.lastname: Kübler
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Veldwijk
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Carsten
authors.initials: C
authors.lastname: Herskind
authors.forename: Frank Anton
authors.initials: FA
authors.lastname: Giordano
mesh_terms: D001253:Astrocytes / Q000528:radiation effects*; D001254:Astrocytoma / Q000473:pathology / Q000532:radiotherapy; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D010315:Particle Accelerators; D011878:Radiotherapy / Q000379:methods*; D012062:Relative Biological Effectiveness; D014407:Tumor Cells, Cultured / Q000528:radiation effects*