title: Uncertainty of calculated risk estimates for secondary malignancies after radiotherapy.
abstract: OBJECTIVE
  The significance of risk estimates for fatal secondary malignancies caused by out-of-field radiation exposure remains unresolved because the uncertainty in calculated risk estimates has not been established. This work examines the uncertainty in absolute risk estimates and in the ratio of risk estimates between different treatment modalities.
  
  
  METHODS
  Clinically reasonable out-of-field doses and calculated risk estimates were taken from the literature for several prostate treatment modalities, including intensity-modulated radiotherapy (IMRT), and were recalculated using the most recent risk model. The uncertainties in this risk model and uncertainties in the linearity of the dose-response model were considered in generating 90% confidence intervals for the uncertainty in the absolute risk estimates and in the ratio of the risk estimates.
  
  
  RESULTS
  The absolute risk estimates of fatal secondary malignancy were associated with very large uncertainties, which precluded distinctions between the risks associated with the different treatment modalities considered. However, a much smaller confidence interval exists for the ratio of risk estimates, and this ratio between different treatment modalities may be statistically significant when there is an effective dose equivalent difference of at least 50%. Such a difference may exist between clinically reasonable treatment options, including 6-MV IMRT versus 18-MV IMRT for prostate therapy.
  
  
  CONCLUSIONS
  The ratio of the risk between different treatment modalities may be significantly different. Consequently risk models and associated risk estimates may be useful and meaningful for evaluating different treatment options. The calculated risk of secondary malignancy should be considered in the selection of an optimal treatment plan.
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. sfkry@mdanderson.org
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kry
authors.forename: David
authors.initials: D
authors.lastname: Followill
authors.forename: R Allen
authors.initials: RA
authors.lastname: White
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Kuban
authors.forename: Mohammad
authors.initials: M
authors.lastname: Salehpour
mesh_terms: D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D018570:Risk Assessment; D035501:Uncertainty