Date of Award

8-20-2004

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Steven E Pfau MD

Abstract

Intravascular brachytherapy is the primary treatment for coronary in-stent restenosis. We hypothesized that differences in dose delivered to target may contribute to treatment failures. We compared dose distribution between arteries that developed recurrent restenosis (treatment failures) and those that remained patent at nine-months (treatment success). A cohort of 207 patients receiving brachytherapy for coronary in-stent restenosis with four radiation delivery devices was followed to identify treatment failures and successes. This cohort was examined to establish which patient and lesion characteristics had an effect on outcome. A nested case-control construct was then used in which treatment failures (n=14) were compared 1:2 to treatment successes (n=28) matched by two variables: radiation delivery system and angiographic pattern of in-stent restenosis. At baseline, the groups had similar patient and lesion characteristics. The dose absorbed by 90% of the artery encompassed by the external elastic membrane (D90EEM) was calculated using intravascular ultrasound (IVUS) images taken at 2-mm intervals along the treated lesion. Dose calculations were performed using dose kernel integration techniques; the dose kernels were generated from Monte Carlo simulations. The mean D90EEM minimum dose in treatment failures was 7.46±1.98 Gy, while for treatment success the mean D90EEM minimum dose was significantly higher: 8.87±1.13 Gy (p=0.007). Using a dose threshold of 8.4 Gy, a D90EEM minimum dose ≤ 8.4 Gy occurred in 13 (93%) patients with treatment failure, but in only 9 (32%) with treatment success (p≤0.001). No confounding variables were found to be statistically significant. In conclusion, current brachytherapy dose prescriptions result in significant inter- and intra-lesion variation in dose at the EEM. Arteries that receive ≤ 8.4 Gy at any point along the EEM are more likely to be treatment failures. IVUS guided dosimetry may be critical to assure adequate dose regardless of radiation delivery system.

Comments

This is an Open Access Thesis.

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