title: Impact of millimeter-level margins on peripheral normal brain sparing for gamma knife radiosurgery.
abstract: OBJECTIVE
  To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery.
  
  
  METHODS
  A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added.
  
  
  RESULTS
  Confirmatory correlation between the nominal target radius (ie, RT) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/RT, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R(2) >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/RT values for the target.
  
  
  CONCLUSIONS
  Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California. Electronic address: lijunma@radonc.ucsf.edu.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sahgal
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: David A
authors.initials: DA
authors.lastname: Larson
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Dilini
authors.initials: D
authors.lastname: Pinnaduwage
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Shannon
authors.initials: S
authors.lastname: Fogh
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Igor
authors.initials: I
authors.lastname: Barani
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Jean
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Michael
authors.initials: M
authors.lastname: McDermott
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California.
authors.forename: Penny
authors.initials: P
authors.lastname: Sneed
mesh_terms: D000465:Algorithms; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery*; D019583:Dose Fractionation, Radiation; D006801:Humans; D007103:Immobilization / Q000295:instrumentation; D009336:Necrosis; D059351:Organ Sparing Treatments / Q000379:methods*; D016634:Radiosurgery / Q000295:instrumentation / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D047368:Tumor Burden