title: Risk of radiation-induced secondary rectal and bladder cancer following radiotherapy of prostate cancer.
abstract: BACKGROUND
  An elevated risk of radiation-induced secondary cancer (SC) has been observed in prostate cancer patients after radiotherapy (RT), rising to as high as one in 70 patients with more than 10 years follow-up. In this study we have estimated SC risks following RT with both previous and contemporary techniques, including proton therapy, using risk models based on different dose-response relationships.
  
  
  METHODS
  RT plans treating the prostate and seminal vesicles with either conformal radiotherapy (CRT), volumetric modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) were created for 10 patients. The risks of radiation-induced cancer were estimated for the bladder and rectum using dose-response models reflecting varying degrees of cell sterilisation: a linear model, a linear-plateau model and a bell-shaped model also accounting for fractionated RT.
  
  
  RESULTS
  The choice of risk models was found to rank the plans quite differently, with the CRT plans having the lowest SC risk using the bell-shaped model, while resulting in the highest risk applying the linear model. Considering all dose-response scenarios, median relative risks of VMAT versus IMPT were 1.1-1.7 for the bladder and 0.9-1.8 for the rectum. Risks of radiation-induced bladder and rectal cancers were lower from VMAT if exposed at 80 years versus IMPT if exposed at 50 years.
  
  
  CONCLUSIONS
  The SC risk estimations for the bladder and rectum revealed no clear relative relationship between the contemporary techniques and CRT, with divergent results depending on choice of model. However, the SC risks for these organs when using IMPT were lower or comparable to VMAT. SC risks could be assessed when considering referral of prostate cancer patients to proton therapy, taking also general patient characteristics, such as age, into account.
authors.affiliation: a Department of Oncology and Medical Physics , Haukeland University Hospital , Bergen , Norway.|b Department of Physics and Technology , University of Bergen , Bergen , Norway.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Stokkevåg
authors.affiliation: a Department of Oncology and Medical Physics , Haukeland University Hospital , Bergen , Norway.
authors.forename: Grete M
authors.initials: GM
authors.lastname: Engeseth
authors.affiliation: a Department of Oncology and Medical Physics , Haukeland University Hospital , Bergen , Norway.
authors.forename: Liv B
authors.initials: LB
authors.lastname: Hysing
authors.affiliation: b Department of Physics and Technology , University of Bergen , Bergen , Norway.
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Ytre-Hauge
authors.affiliation: a Department of Oncology and Medical Physics , Haukeland University Hospital , Bergen , Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Ekanger
authors.affiliation: c Department of Medical Physics , Aarhus University/Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Ludvig P
authors.initials: LP
authors.lastname: Muren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000209:etiology*