title: Enhanced in vitro radiosensitivity of skin fibroblasts in two patients developing brain necrosis following AVM radiosurgery: a new risk factor with potential for a predictive assay.
abstract: OBJECTIVE
  Radiosurgery is an effective treatment for arteriovenous malformations (AVM) with a low risk of developing brain necrosis. Models have been developed to predict the risk of complications. We postulated that genetic differences in radiosensitivity may also be a risk factor.
  
  
  METHODS
  Fibroblast cultures were established from skin biopsies in two AVM patients developing radiation necrosis. The results of clonogenic survival assays were compared to a parallel study with two groups of cancer patients treated with radiation: 1) patients without late side effects; 2) patients experiencing severe late sequelae.
  
  
  RESULTS
  The survival fraction at 2 Gy (SF2) of the 2 AVM patients was 0.17 (0.14-0.19) and 0.18 (0.14-0.22). The SF2's of the cancer patients ranged between 0.25-0.38 (mean = 0.31) for the control group, and between 0. 10-0.20 (mean = 0.17) for the hypersensitive group. The SF2's of the AVM patients who developed brain necrosis were comparable to that of the hypersensitive group (p = 0.85) but significantly lower than the control group (p = 0.05).
  
  
  CONCLUSIONS
  The two patients who developed radiation necrosis demonstrate increased fibroblast radiosensitivity. The SF2 of skin fibroblasts may potentially be used as a predictive assay to detect patients at risk for brain necrosis.
authors.affiliation: Radiation Oncology, Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada. smalone@cancercare.on.ca
authors.forename: S
authors.initials: S
authors.lastname: Malone
authors.forename: G P
authors.initials: GP
authors.lastname: Raaphorst
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.forename: A
authors.initials: A
authors.lastname: Girard
authors.forename: G
authors.initials: G
authors.lastname: Alsbeih
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000601:surgery*; D008297:Male; D009336:Necrosis; D011237:Predictive Value of Tests; D011832:Radiation Injuries / Q000150:complications*; D011836:Radiation Tolerance; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012867:Skin / Q000166:cytology*