title: Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: dose/volume-response relations.
abstract: OBJECTIVE
  . To evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging.
  
  
  METHODS
  . Data from 73 AVM patients who had stereotactic Linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three levels with respect to the extent of the image change (small, intermediate, and large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm(3) (Dmean20) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean20 and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape logistic function and characterized by DV(50), the dose for a 50% incidence, and the slope parameter k.
  
  
  RESULTS
  . Dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV(50) values of fitted dose/volume-response curves for tissue changes of large extent (e.g., V12(50) = 22.0 +/- 2.6 cm(3) and Dmean20(50) = 17.8 +/- 2.0 Gy for the combined endpoint of edema and/or BBBB) were significantly higher than those for small tissue changes (V12(50) = 4.0 +/- 0.3 cm(3) and Dmean20(50) = 7.6 +/- 0.3 Gy).
  
  
  CONCLUSIONS
  . The derived dose/volume-response relations allow to quantitatively assess the risk of radiation-induced changes of brain tissue after radiosurgery in AVM patients. However, further understanding of the mechanism leading to brain tissue changes and their correlation with the desired obliteration is required. This knowledge will eventually help to optimize radiosurgical treatments in AVM patients.
authors.affiliation: Department of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg, Germany. sabine.levegruen@uni-essen.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Levegrün
authors.forename: Holger
authors.initials: H
authors.lastname: Hof
authors.forename: Marco
authors.initials: M
authors.lastname: Essig
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlegel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D001921:Brain / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000532:radiotherapy*; D008297:Male; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D016634:Radiosurgery / Q000009:adverse effects*; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors