title: A numerical simulation of organ motion and daily setup uncertainties: implications for radiation therapy.
abstract: OBJECTIVE
  In radiotherapy planning, the clinical target volume (CTV) is typically enlarged to create a planning target volume (PTV) that accounts for uncertainties due to internal organ and patient motion as well as setup error. Margin size clearly determines the volume of normal tissue irradiated, yet in practice it is often given a set value in accordance with a clinical precedent from which variations are rare. The (CTV/PTV) formalism does not account for critical structure dose. We present a numerical simulation to assess (CTV) coverage and critical organ dose as a function of treatment margins in the presence of organ motion and physical setup errors. An application of the model to the treatment of prostate cancer is presented, but the method is applicable to any site where normal tissue tolerance is a dose-limiting factor.
  
  
  METHODS
  A Monte Carlo approach was used to simulate the cumulative effect of variation in overall tumor position, for individual treatment fractions, relative to a fixed distribution of dose. Distributions of potential dose-volume histograms (DVHs), for both tumor and normal tissues, are determined that fully quantify the stochastic nature of radiotherapy delivery. We introduce the concept of Probability of Prescription Dose (PoPD) isosurfaces as a tool for treatment plan optimization. Outcomes resulting from current treatment planning methods are compared with proposed techniques for treatment optimization. The standard planning technique of relatively large uniform margins applied to the CTV, in the beam's eye view (BEV), was compared with three other treatment strategies: (a) reduced uniform margins, (b) nonuniform margins adjusted to maximize normal tissue sparing, and (c) a reduced margin plan in which nonuniform fluence profiles were introduced to compensate for potential areas of reduced dose.
  
  
  RESULTS
  Results based on 100 simulated full course treatments indicate that a 10 mm CTV to PTV margin, combined with an additional 5 mm dosimetric margin, provides adequate CTV coverage in the presence of known treatment uncertainties. Nonuniform margins can be employed to reduce dose delivered to normal tissues while preserving CTV coverage. Nonuniform fluence profiles can also be used to further reduce dose delivered to normal tissues, though this strategy does result in higher dose levels delivered to a small volume of the CTV and normal tissues.
  
  
  CONCLUSIONS
  Monte Carlo-based treatment simulation is an effective means of assessing the impact of organ motion and daily setup error on dose delivery via external beam radiation therapy. Probability of Prescription Dose (PoPD) isosurfaces are a useful tool for the determination of nonuniform beam margins that reduce dose delivered to critical organs while preserving CTV dose coverage. Nonuniform fluence profiles can further alter critical organ dose with potential therapeutic benefits. Clinical consequences of this latter approach can only be assessed via clinical trials.
authors.affiliation: Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Killoran
authors.forename: H M
authors.initials: HM
authors.lastname: Kooy
authors.forename: D J
authors.initials: DJ
authors.lastname: Gladstone
authors.forename: F J
authors.initials: FJ
authors.lastname: Welte
authors.forename: C J
authors.initials: CJ
authors.lastname: Beard
mesh_terms: D000465:Algorithms; D006801:Humans; D008297:Male; D009010:Monte Carlo Method; D009068:Movement; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012007:Rectum; D014057:Tomography, X-Ray Computed; D001743:Urinary Bladder