1. Radiation for restenosis: the dark side of arteries Robert S Schwartz MD Professor of Medicine Mayo Clinic Rochester, MN

2. Stimulation of neointima within an irradiated artery Figure 1

3. Minimal neointimal neoplasia post stent placement Figure 2

4. External beam radiation major US center 11 patient pilot study 8 Gy external beam radiation 11/11 restenosis the restenosis rate was 100%

5. Radiation injury to blood vessels capillary injury is greatest obliteration of capillaries one mechanism of anti-tumor action thrombosis, rupture, fibrosis occasionally lymphocytic vasculitis venous lesions are uncommon

6. Induction of neointima post external beam radiation Figure 3

7. Venezuelan study the late loss is too high Figure 4: late loss (millimeters) 0.44 0.40 0.33 0.32 0.28 0.27 0.26 0.25 CondadoLRTMARCATORBENESTENTHELVETICACARPORTMERCATORPARK Condado J, Circulation 1997;96:727

8. 3 questions on radiation Q: Is arterial radiation feasible? A: “Yes” Q: Is it safe? A: “We doubt it” Q: Is it efficacious? A:”We don’t think so” Serruys et al, Circulation 1997;96:709-712

9. Neointimal hyperplasia at former sites of radiation Figure 5

10. PREVENT trial Figure 6 Restenosis in the treated segment Raizner et al, PREVENT trial 1998 9.1% 22.2% 0.0% 25.0% P 32Control

11. PREVENT trial Figure 7 Restenosis in the adjacent segment Raizner et al, PREVENT trial 1998 22.7% 11.1% 0.0% 25.0% P 32Control

12. PREVENT trial Figure 8 Restenosis in the treated and adjacent segments Raizner et al, PREVENT trial 1998 22.7% 22.2% 0.0% 25.0% P 32Control

13. BERT trial restenosis rate of 17% 6 patients with an “edge problem” overall restenosis rate of 25%

14. Beta emitting stents and restenosis Figure 9 Restenosis in the treated and adjacent segments 56.0% (10/18) 39.0% (11/28) 45.0% (5/11) 50.0% (1/2) 0.75-3 uCi3-6 uCi 6-12 uCi12-20 uCi

15. Cellular neointimal hyperplasia of in-stent restenosis Figure 10

16. Neointimal hyperplasia at former sites of radiation Figure 11

17. European registry, 150 patients PTCA up to 2 vessels Beta-Cath system, 90-Sr/Y 12,14,16 Gy to 2 mm from source target vessel restenosis 30% late loss index 13% Serruys, 1999 The BRIE trial

18. Human coronary artery thrombus in situ Figure 12

19. Multi-layered thrombus in a pig coronary artery Figure 13 Old thrombus New thrombus Absence of neointima

20. Intracoronary beta radiation Figure 14 Effects of intracoronary beta-radiation after 6 months in stented vessels 2.84 3.16 0 1 2 3 4 controltreated Neointimal area (mm 2 ) P=NS

21. Figure 15 Angiographic restenosis rate 54% 17% controlradiated SCRIPPS trial

22. Figure 16 The SCRIPPS radiated group, a long term analysis SCRIPPS trial P=NS

23. Figure 17 GAMMA-I 6 month follow-up GAMMA-I in-stent measures

24. EVGActin Heat injury Figure 18