title: Modelling of organ-specific radiation-induced secondary cancer risks following particle therapy.
abstract: Radiation-induced cancer is a serious late effect that may follow radiotherapy. A considerable uncertainty is associated with carcinogenesis from photon-based treatment, and even less established when including relative biological effectiveness (RBE) for particle therapy. The aim of this work was therefore to estimate and in particular explore relative risks (RR) of secondary cancer (SC) following particle therapy as applied in treatment of prostate cancer.
  
  
  
  RRs of radiation-induced SC in the bladder and rectum were estimated using a bell-shaped dose-response model incorporating RBE and fractionation effects. The risks from volumetric modulated arc therapy (VMAT) were compared to intensity-modulated proton therapy (IMPT) and scanning carbon ions for ten patients.
  
  
  
  The mean estimated RR (95% CI) of SC for VMAT/C-ion was 1.31 (0.65-2.18) for the bladder and 0.58 (0.41-0.80) for the rectum. Corresponding values for VMAT/IMPT were 1.72 (1.06-2.37) and 1.10 (0.78-1.43). The radio-sensitivity parameter α had the strongest influence on the results with decreasing RR for increasing values of α.
  
  
  
  Based on the wide spread in RR between patients and variations across the included parameter values, the risk profiles of the rectum and bladder were not dramatically different for the investigated radiotherapy techniques.
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway; Department of Physics and Technology, University of Bergen, Norway. Electronic address: camilla.hanquist.stokkevag@helse-bergen.no.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Stokkevåg
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Fukahori
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan; Department of Radiation Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Nomiya
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Naruhiro
authors.initials: N
authors.lastname: Matsufuji
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Grete May
authors.initials: GM
authors.lastname: Engeseth
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Liv B
authors.initials: LB
authors.lastname: Hysing
authors.affiliation: Department of Physics and Technology, University of Bergen, Norway.
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Ytre-Hauge
authors.affiliation: Department of Physics and Technology, University of Bergen, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Rørvik
authors.affiliation: Department of Physics and Technology, University of Bergen, Norway.
authors.forename: Artur
authors.initials: A
authors.lastname: Szostak
authors.affiliation: Department of Medical Physics, Aarhus University/Aarhus University Hospital, Denmark.
authors.forename: Ludvig P
authors.initials: LP
authors.lastname: Muren
mesh_terms: D019583:Dose Fractionation, Radiation; D006801:Humans; D008297:Male; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D058958:Organs at Risk / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012004:Rectal Neoplasms / Q000209:etiology*; D012007:Rectum / Q000528:radiation effects; D012306:Risk; D001743:Urinary Bladder / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000209:etiology*
keywords: Carbon ion; Particle therapy; Prostate; Proton; Secondary cancer