title: Do we need fractionation-corrected doses in sequential two-phase treatments? A quantification of dose differences between non-corrected and corrected combined non-uniform dose distributions in normal tissue.
abstract: BACKGROUND
  For many tumour sites, external beam radiation therapy (EBRT) is delivered with a sequential two-phase treatment regime. Yet, there is a lack of consensus of how to add two different non-uniform dose distributions in order to evaluate the late radiation effect for normal tissue. The purpose of this novel investigation is to quantify the dose differences between non-corrected and fractionation-corrected combined non-uniform dose distributions.
  
  
  METHODS
  We used a model of an organ at risk (OAR) located in six different positions relative the treated volume giving 16 clinically representative two-phase treatment situations (46 Gy + 22 Gy). The linear-quadratic model was applied to correct for fractionation effects in each voxel before the doses were added. Dose differences were quantified using mean and maximum doses with corresponding fractionation-corrected doses as reference.
  
  
  RESULTS
  Non-corrected doses were higher than fractionation-corrected doses in all treatment situations (mean dose: p<0.001; maximum dose: p=0.003). With the OAR outside the treated volume, non-corrected doses were 3-6 Gy higher representing 10-50% of the reference dose (10-25 Gy); with the OAR included in the treated volume, 1-6 Gy higher representing 1-15% (30-60 Gy). Mean dose differences were generally larger than maximum dose differences.
  
  
  CONCLUSIONS
  Substantial dose differences were present in all of the simulated treatment situations but more apparent when the OAR was located outside the treated volume in both phases. Our findings require verification in clinical cases but nevertheless indicate a need for fractionation-corrected doses in two-phase treatments both in the daily clinical routine as well as in the modelling of late radiation effects. Our data suggest that adjusting for fractionation effects would lead to lower tolerance doses than currently suggested, in particular for OARs with parallel tissue architecture.
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska University Hospital, University of Gothenburg, Göteborg, Sweden. caroline.olsson@vgregion.se
authors.forename: Caroline
authors.initials: C
authors.lastname: Olsson
authors.forename: Karl-Axel
authors.initials: KA
authors.lastname: Johansson
mesh_terms: D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008432:Mathematical Computing; D011878:Radiotherapy / Q000379:methods; D011880:Radiotherapy Planning, Computer-Assisted; D012062:Relative Biological Effectiveness