Required treatment margin for coronary endovascular brachytherapy with iridium-192 seed ribbon

Preliminary clinical trials (SCRIPPS I, WRIST and Gamma 1) employing catheter-based endovascular brachytherapy (EVBT) with iridium-192 (Ir-192) seeds show promising results in reducing restenosis after coronary intervention. Failure analysis of these studies showed a significant number of restenosis at the treatment margin called "edge effect." The objective of this study is to investigate the factors that contribute to the adequacy of treatment margin.

The factors contributing to the margins are penumbra effect at the end of the seed train, uncertainty in target localization, longitudinal seed movement during cardiac cycle and barotrauma due to stent deployment. The magnitudes of the penumbra effect, which refers to the tapering off the prescribed isodose line near the ends of the source train, were calculated for various source lengths of Ir-192 seed ribbon using AAPM TG-43 algorithm. Uncertainty in target localization refers to the fact that the visual estimation of proximal and distal extent of the injury is not accurate, and this can be obtained by comparing the "estimate" from the interventional cardiologist with careful review of the cine-angiogram. Longitudinal seed movements relative to the coronary vessel during the cardiac cycle were determined by frame-by-frame reviewing cine-angiograms of 30 patients. The proximal and distal source points were measured in reference to branching vessels during the contrast phase of the cine-angiogram. The maximum proximal and distal longitudinal movement was captured and source displacement was measured from the closest proximal and distal branching vessel. Barotrauma, additional injury to the vessel arising from the stent deployment balloon, was obtained by reviewing specifications from commercially available stent delivery systems.

The penumbra effect ranges from 3.9 to 4.5 mm for 6-22 Ir-192 seed ribbons. The uncertainty in target localization is within 3 mm for our interventional cardiologists. The results of seed movements were categorized by three major coronary vessels and by proximal versus distal ends. The mean and standard deviation of seed movement are 1.1 and 0.8 mm, respectively. The average length of barotrauma beyond the stent margins for reviewed stents was 1.7 mm, ranging from 0.5 to 2.5 mm.

A minimum of 8-mm treatment margin is recommended for coronary vascular brachytherapy with Ir-192 seed ribbon. This was derived by considering the above contributing factors. Excessive margins should be avoided due to possible increase risk of late effect. By providing adequate treatment margins, one can avoid geographic miss; hence, one can further improve the effect of EVBT in reducing restenosis.