title: Inclusion of a variable RBE into proton and photon plan comparison for various fractionation schedules in prostate radiation therapy.
abstract: OBJECTIVE
  A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction, and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions.
  
  
  METHODS
  Photon and proton dose plans were created for three generic prostate cancer cases. Three BED3Gyequivalent schedules were studied, 78, 57.2, and 42.8 Gy in 39, 15, and 7 fractions, respectively. The proton plans were optimized assuming a constant RBE of 1.1. By using the Monte Carlo calculated dose-averaged LET (LETd) distribution and assuming α/β values on voxel level, three variable RBE models were applied to the proton dose plans. The impact of the variable RBE was studied in the plan comparison, which was based on the dose distribution, DVHs, and normal tissue complication probabilities (NTCP) for the rectum. Subsequently, the physical proton dose was reoptimized for each proton plan based on the LETddistribution, to achieve a homogeneous RBE-weighted target dose when applying a specific RBE model and still fulfill the clinical goals for the rectum and bladder.
  
  
  RESULTS
  All the photon and proton plans assuming RBE = 1.1 met the clinical goals with similar target coverage. The proton plans fulfilled the robustness criteria in terms of range and setup uncertainty. Applying the variable RBE models generally resulted in higher target doses and rectum NTCP compared to the photon plans. The increase was most pronounced for the fractionation dose of 2 Gy(RBE), whereas it was of less magnitude and more dependent on model and α/β assumption for the hypofractionated schedules. The reoptimized proton plans proved to be robust and showed similar target coverage and doses to the organs at risk as the proton plans optimized with a constant RBE.
  
  
  CONCLUSIONS
  Model predicted RBE values may differ substantially from 1.1. This is most pronounced for fractionation doses of around 2 Gy(RBE) with higher doses to the target and the OARs, whereas the effect seems to be of less importance for the hypofractionated schedules. This could result in misleading conclusions when comparing proton plans to photon plans. By accounting for a variable RBE in the optimization process, robust and clinically acceptable dose plans, with the potential of lowering rectal NTCP, may be generated by reoptimizing the physical dose. However, the direction and magnitude of the changes in the physical proton dose to the prostate are dependent on RBE model and α/β assumptions and should therefore be used conservatively.
authors.affiliation: Department of Physics, Medical Radiation Physics, Stockholm University, Stockholm, 17176, Sweden.|RaySearch Laboratories, Stockholm, 11134, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Ödén
authors.affiliation: RaySearch Laboratories, Stockholm, 11134, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Eriksson
authors.affiliation: Department of Physics, Medical Radiation Physics, Stockholm University, Stockholm, 17176, Sweden.|Department of Oncology and Pathology, Medical Radiation Physics, Karolinska Institutet, Stockholm, 17176, Sweden.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Toma-Dasu
mesh_terms: D000465:Algorithms; D019583:Dose Fractionation, Radiation; D004735:Energy Transfer; D006801:Humans; D016014:Linear Models; D008297:Male; D009010:Monte Carlo Method; D058958:Organs at Risk; D017785:Photons / Q000627:therapeutic use*; D011467:Prostate / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D061766:Proton Therapy / Q000379:methods*; D011832:Radiation Injuries / Q000517:prevention & control; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D012007:Rectum / Q000528:radiation effects; D012062:Relative Biological Effectiveness; D001743:Urinary Bladder / Q000528:radiation effects; D011522:Protons
chemical_list: D011522:Protons
keywords: 
  RBE
  ; biological modeling; fractionation; prostate radiotherapy; proton therapy