title: Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: correlation with dose distribution parameters.
abstract: OBJECTIVE
  To investigate the correlation of radiation-induced changes of brain tissue after radiosurgery in patients with cerebral arteriovenous malformations (AVMs) with treatment planning and dose distribution parameters.
  
  
  METHODS
  The data from 73 AVM patients with complete follow-up information who underwent stereotactic linear accelerator radiosurgery at our institution between 1993 and 1998 were analyzed. Patients were treated with 11-14 noncoplanar fields shaped by a micromultileaf collimator. A median dose of 19 Gy (range, 13.3-22 Gy) was prescribed to the 80% isodose, which completely encompassed the target. Patients were followed at 3-month intervals the first year and then every 6 months with MRI and neurologic examinations. No patient developed radiation necrosis. The end point of radiation-induced tissue changes on follow-up neuroimaging (i.e., edema, blood-brain barrier breakdown [BBBB], and edema and/or BBBB combined) was evaluated. Each end point was further differentiated into four levels with respect to the extent of the image change (i.e., small, intermediate, large, and very large). The correlation of each end point was investigated for several treatment planning parameters, including prescribed dose and the absolute size of the AVM target volume. In addition, a number of dose-volume variables were calculated from each patient's dose distribution in the brain, including the mean dose to a specified volume of 16 and 20 cm(3) that was given the highest dose (Dmean16 and Dmean20, respectively), and the absolute and percentage of brain volume (including the AVM target) receiving a dose of at least 8, 10, and 12 Gy (V8-V12, and V8(rel)-V12(rel), respectively). These parameters were also determined excluding the AVM target volume from the considered volume (subscript "excl"). The correlation of all treatment planning and dose-volume parameters with outcome was assessed in univariate Cox proportional hazards models. The results were assessed by p values (statistical significance for p < or =0.05), residual deviance (ResDev) of the fits, and odds ratios.
  
  
  RESULTS
  The prescribed dose was not predictive of outcome (p >0.05 for all end points). The AVM target volume correlated significantly with large edema, as well as large edema and/or BBBB. V12 and Dmean20 were significantly associated with all end points, except very large edema and large BBBB. Patients with V12 of 27.6 cm(3) (Dmean20 of 18.9 Gy) had a 2.8-fold (fourfold) higher risk of developing edema and/or BBBB with large extent than those with V12 of 4.2 cm(3) (Dmean20 of 8.4 Gy). For all end points, V12(rel) correlated worse with outcome compared with V12 (e.g., end point of large edema and/or BBBB: ResDev = 85.8 and 86.5 for V12 and V12(rel), respectively). Excluding the AVM target volume from the considered irradiated volume led to only small changes in the resulting correlations (e.g., end point of small edema and/or BBBB: ResDev = 99.0 and 98.7 for V12 and V12(excl), respectively, and ResDev = 96.1 and 96.1 for Dmean20 and Dmean20(excl), respectively). Throughout the analysis, V8-V12, Dmean20, and Dmean16 yielded similar results and none of these parameters could be favored over the others.
  
  
  CONCLUSIONS
  Radiation-induced changes of brain tissue after AVM radiosurgery can be well predicted by single dose distribution parameters that are a function of both dose and volume. These can be used to quantify dose-volume response relations. Studies of this nature will eventually help to improve our current understanding of the mechanisms leading to radiation-induced tissue changes after AVM radiosurgery and to optimize radiosurgery treatment planning.
authors.affiliation: Department of Medical Physics, Deutsches Krebsforschungszentrum, Heidelberg, Germany. s.levegruen@dkfz.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: D000293:Adolescent; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000528:radiation effects; D001921:Brain / Q000528:radiation effects*; D001929:Brain Edema / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000473:pathology*; D016634:Radiosurgery / Q000009:adverse effects* / Q000295:instrumentation / Q000379:methods; D011879:Radiotherapy Dosage