title: Optimization of dose prescription protocol and its impact on delivered dose and vascular response after beta-radiation for in-stent restenosis. A randomized trial with serial volumetric intravascular ultrasound and dose volume histograms.
abstract: OBJECTIVE
  The incidence of restenosis within stented segment after intravascular brachytherapy with recommended dose prescription protocols is up to 25%. Therefore, we designed a randomized trial comparing recommended dose prescription protocol with dosing adjusted for the source-to-target distance.
  
  
  METHODS
  Fifty-one in-stent restenosis (ISR) lesions in 48 patients underwent centered source beta-irradiation with serial intravascular ultrasound. Patients randomly received 20 Gy at 1 mm either beyond lumen surface [n=25, standard group (S)] or external elastic membrane [n=26, dosing-adjusted (DA) group]. Minimum dose absorbed by 90% of adventitia (DV(90%Adv)) was calculated.
  
  
  RESULTS
  DV(90%Adv) was higher for the DA group than for the S group (21.63+/-5.67 vs. 12.05+/-4.88 Gy, P<.001). After 8.9+/-4.5 months there was complete lumen preservation in DA vs. lumen decrease subsequent to neointimal hyperplasia (NIH) in S group (0.10+/-1.20 vs. -0.61+/-1.29 mm3/mm, P<.05). Vessel volume increased significantly in the DA group and was unchanged in S group (+1.73, P=.002 vs. 0.14 mm3/mm, P=NS). DV(90%Adv) correlated inversely with NIH volume and positively with vessel volume change (r=-.405, P=.007 and r=.363, P=.017, respectively).
  
  
  CONCLUSIONS
  For beta-irradiation of ISR, dosing adjusted for the source-to-target distance leads to significant increase in target delivered doses, which is associated with complete NIH inhibition and induction of positive vessel remodeling.
authors.affiliation: Institute of Cardiology, Warsaw, Poland. witkowski@hbz.pl
authors.forename: Adam
authors.initials: A
authors.lastname: Witkowski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Chmielak
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kalińczuk
authors.forename: Jerzy
authors.initials: J
authors.lastname: Pregowski
authors.forename: Cezary
authors.initials: C
authors.lastname: Kepka
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kruk
authors.forename: Jarosław
authors.initials: J
authors.lastname: Lyczek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bulski
authors.forename: Maria
authors.initials: M
authors.lastname: Kawczyńska
authors.forename: Anna
authors.initials: A
authors.lastname: Kulik
authors.forename: Jacek
authors.initials: J
authors.lastname: Owczarczyk
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyłło
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018709:Statistics, Nonparametric; D015607:Stents; D018084:Ultrasonography, Interventional