UAE: Does the choice of embolic matter?

1. UAE: Does the choice of embolic matter? John C. Lipman, MD, FSIR Atlanta Interventional Institute Marietta, Georgia

2. In Conclusion • Yes

3. Why does embolic choice matter? • Successful long-term outcome is defined by: • Symptom control • No recurrent growth of fibroids. • Imaging documentation by contrast-enhanced MRI. • Absence of re-interventions • Fibroids need to completely infarct to avoid recurrence. • Technical goal of UAE is to infarct all the fibroids.

4. Causes For UAE Failure • 1. Technique issues • 2. Collateral supply • 3. Choice of embolic

5. Perfusion of fibroids after UAE: predictor of outcome • DeSouza (Rad 2002 (2); 222: 367-74): perfusion of myometrium & dominant fibroids pre & post UAE (1mo/4mo). • Pelage (SIR ’05 abstract) • -79 women with MRI @ 24’, 6m,12m, 24m. • -Those completely infarcted @ 24’ stayed infarcted. • -This group had significant clinical improvement vs. incompletely infarcted group. • -No difference in uterine & dominant volume reduction between groups.

6. No Symptom Recurrence Complete Fibroid Infarction Baseline 3 Months 1 Year 2 Years 3 years

7. Early RecurrenceIncomplete Fibroid InfarctionRecurrent symptoms at 2.5 years post-embolization (Radiology 2004;230:803-9). Pre 3 mo 1 year 2 years 3 years 4 years

8. Late RecurrenceOld and New Fibroids Baseline 4 Months 26 Months 46 months

9. Currently materials in use in United States and Europe • Particle PVA (Contour, other brands) • Tris-acryl Gelatin Microspheres (Embospheres) • Tris-acryl Gelatin Microspheres AU (Embogold) • Spherical PVA (Contour SE) • Spherical PVA hydrogel (Bead Block) • Gelatin sponge (Gelfoam)

10. Particle PVA (Contour, others) • Longest use of any product. • Relatively inexpensive. • Hard to inject, can easily clog microcatheters. • Initial experience in UAE all based on particle PVA. • Early suspicions that PVA caused more pain than necessary.

11. Embosphere® Microspheres • First embolic to win FDA clearance specifically for uterine embolization. • Easy to inject. • Demonstrated effective in randomized comparison to particle PVA. • More expensive than particle PVA. • Allows easier control over endpoint (more gradual occlusion). • Believed to cause less pain than PVA (anecdotal). Papers by Ryu, Spies showed no difference.

12. Imaging Outcome after TAGM • Banovac (Spies) JVIR ’02; 13: 681-7. • -61 fibroids, 23 pts. • -Pre & 3-4 month post MRI. • -54/61 (89%) & 21/23 dominant (91%) were completely devascularized.

13. PVA Particles vs Embospheres • Randomized comparison study of embolics*. • 100 subjects (54 TAGM, 46 PVA) • Outcome measures: • Short-term pain (VAS scale), recovery • Symptom, quality of life change 3 months • Imaging outcome at 3 months. *Spies JB, et al. Polyvinyl Alcohol Particles and Tris-acryl gelatin Microspheres for Uterine Artery Embolization for Leiomyomas:Results of a Randomized Comparative Study. J Vasc Intervent Radiol 2004;15;793-800.

14. TAGM vs. PVA • Statistically significant : TAGM more cc used (9.4 vs 3 cc), PVA higher cath occlusion (28% vs 4%). TAGM had higher symptom score change (started off worse). PVA had more complete infarction of dominant fibroid (95% vs 82%). • Equivalent: Spasm rate, pain scores 1wk & 3m, narcotic requirements, symptom scores 1wk & 3m. Qof L total score. Amenorrhea rate. • Trend: More uninfarcted nondominant fibroids with PVA (20% vs. 8%).

15. ResultsProcedure Details

16. ResultsShort-term Outcomes

17. Results3 Months

18. ResultsImaging Outcome

19. Contour SE • Marketed as a Embospheres-like sphere made of PVA. Easy to inject. • Specific-label approval by FDA for uterine embolization. • Questions have arisen about effectiveness • Repeated study for sPVA vs Embospheres* • Randomized to either embolic • Patient, research nurse blinded to embolic • Review of pre and post embo MRIs blinded to embolic. * Spies JB, et al. Spherical Polyvinyl Alcohol versus Tris-acryl Gelatin Microspheres for Uterine Artery Embolization for Leiomyomas: Results of a Limited Randomized Comparative Study. J Vasc Intervent Radiol, in press.

20. Results • 36 patients enrolled: 17 with Contour SE and 19 with Embospheres. • Enrollment stopped based on initial findings. • No difference in short-term measures. • Embospheres advantage quality of life scores at 3 months. (91.9 vs 78.1, p= 0.02). • Among 19 patients with imaging follow-up, Contour less likely to infarct all fibroids (1 of 14 for Contour vs 6 of 11 for Embospheres, P= 0.02). • Contour SE had greater percent unifarcted (mean 48% for Contour SE vs 5% for Embospheres, P<0.001).

21. sPVA 90% uninfarcted Pre Post

22. Embosphere 30% uninfarcted Pre Post

23. sPVA vs. PVA • Levin SIR ’05 presentation: • -23 pts. 500-700 sPVA and 23 350-500 PVA. • -Similar baseline ut. volumes, # or size of fibroids. • -?embo light or stasis. • -sPVA: 3.7 x more likely to have persistently enhancing fibroids than PVA. • -(Ut. size avg. decrease of 16% sPVA & 28% PVA)

24. sPVA • Siskin, SIR’05 presentation: • -124 pts but only 69 had MRI. • -500-700m sPVA to complete stasis. • -100% infarction in only 35/69 (51%).

25. Initial Conclusions • Short term imaging outcome shows frequent poor results from sPVA. • Difference statistically significant (Spies data), although still a small sample. • Likely mechanism is redistribution after embolization. • Primary Contour size was 500-700. Larger size embolic may be more effective, although no published data to support (Pelage unpublished data).

26. Refined Protocol for sPVA • Unpublished data Pelage, SIR ’05 presentation that followed Levin: • -2 groups of 23 pts. • -Grp 1: sPVA, 500-700m, “embo light” • -Grp 2: sPVA, 700-900m & up, embo to stasis • (Increase UA viz 510 cardiac beats & leave catheter in place for 5’ & re-check) • -19/23 (83%) complete fibroid infarction in grp 2 vs. only 2/23 (9%) in grp 1.

27. Bead Block • Similar to spherical PVA. • No clinical studies demonstrating its effectiveness compared to other materials. • Terumo IR Survey: 312 IR professionals polled @ SIR 2005, 72% said that Bead Block is superior to other embolics (26% same, 2% inferior).

28. Bead Block (con’t) • No published studies on its effectiveness. • (Kroencke ISET ’05 presentation: 42 pts, 500-700m up to 6cc then upsize, “embo light” initially then extended study to increase infarction rate by changing to near stasis and upsizing. 74% had 90-100% infarction). • Given concerns regarding spherical PVA, careful assessment of the extent of fibroid infarction with contrast-enhanced MRI essential.

29. Gelfoam • Essentially no published data on its effectiveness. • Abstract by Katsumori et al SIR ‘05 in long-term outcomes. 85 pts (17 lost to f/u, similar symptom control, somewhat less failure @ 5 yr (11.5 vs. 20%). • No data to support contention that since it is temporary agent it is better for patients interested in pregnancy (2 pts pregnant, both miscarried). • May be as likely or more to result in uterine artery occlusion than other materials. • Needs further study.

30. Embogold • Essentially the same as Embospheres but with elemental gold added. • Likely same effectiveness profile as Embospheres. • Associated with recurrent pain, low grade fevers and rash in higher than expected number of UAE patients. • No longer recommended by manufacturer for UAE. • Should not be used for UAE.

31. Conclusions • In early years of UAE, there was little data to suggest that the embolic type impacted outcome. • Recent experience with newer embolics suggests that embolic characteristics do impact effectiveness through incomplete fibroid infarction. • Prior to acceptance of new embolics, need quality imaging data with follow-up contrast-enhanced MRI to insure complete fibroid infarction.