title: The biological effectiveness of intermittent irradiation as a function of overall treatment time: development of correction factors for linac-based stereotactic radiotherapy.
abstract: OBJECTIVE
  Continuous irradiation of relatively short duration as administered in gamma-ray stereotactic radiosurgery (SRS) is biologically not equivalent to the more protracted intermittent exposures during accelerator-based radiosurgery with multiple arcs. Accelerator-based SRS and fractionated stereotactic radiotherapy (SRT) is currently performed with a high degree of variability in equipment and techniques resulting in highly variable treatment delivery times. The present work is designed to quantify the effects of radiation delivery times on biological effectiveness. For this, the intermittent radiation delivery schemes, typical for linac-based SRS/SRT, have been simulated in vitro to derive biological correction factors.
  
  
  METHODS
  The experiments were carried out using U-87MG human glioma cells in suspension at 37 degrees C irradiated with 6 MV X-rays to clinically relevant doses ranging from 6 to 18 Gy, delivered over total irradiation times from 16 min to 3 h. The resulting cell survival data was used to calculate dose correction factors to compensate for wide variations in dose delivery times.
  
  
  RESULTS
  At each total dose level, cell survival increased with increasing total irradiation time. The increase in survival was more pronounced at higher dose levels. At a total dose of 12 Gy, cell survival increased by a factor of 4.7 when irradiation time was increased from 16 to 112 min. Dose correction factors were calculated to allow biologically equivalent irradiations over the range of exposure times. Cells irradiated with corrected total doses of 11.5 Gy delivered incrementally in 16 min up to 13.3 Gy in 112 min were found to exhibit the same survival within the experimental limits of accuracy.
  
  
  CONCLUSIONS
  For a given total dose, variations in dose delivery time typical of SRS/SRT techniques will result in significant changes in cell survival. In the dose range studied, an isoeffect dose correction factor of 2 to 3 cGy/min was shown to compensate for the change in delivery time for U-87 MG human gloma cells in vitro.
authors.affiliation: Radiation Oncology Department, Medical College of Virginia, Richmond 23298-0058, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Benedict
authors.forename: P S
authors.initials: PS
authors.lastname: Lin
authors.forename: R D
authors.initials: RD
authors.lastname: Zwicker
authors.forename: D T
authors.initials: DT
authors.lastname: Huang
authors.forename: R K
authors.initials: RK
authors.lastname: Schmidt-Ullrich
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy; D002470:Cell Survival; D005910:Glioma / Q000532:radiotherapy; D006801:Humans; D011874:Radiometry; D016634:Radiosurgery / Q000592:standards*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D013997:Time Factors; D014407:Tumor Cells, Cultured