1. Focused Ultrasound A Non-Invasive Alternative Robert K. Zurawin, MD
Baylor College of Medicine

2. Focused Ultrasound for Uterine Fibroids
non-invasively ablate fibroid tissue without affecting intervening tissues
MRI used in planning, guidance, & outcome prediction
Incision-less (non-invasive) and re-treatable
No ionizing radiation
High safety profile
No hospitalization
Next day return to work/normal activity
© 2013 by Focused Ultrasound Foundation

3. Principles of FUS Treatment
High intensity focused ultrasound transducer in the table top of the MRI
Treatment performed under conscious sedation
Targeting done using MR image
Treatment monitoring using MR thermometry
Tissue is destroyed following multiple ultrasound sonications
Patient goes home the same day
Indication is for patients with symptomatic fibroids
© 2013 by Focused Ultrasound Foundation

4. Real Time MRI Guidance and Monitoring1 2 5
CLOSED LOOP THERAPY
Imaging for precise tumor targeting
Beam path visualization for controlled treatment 4 3
Post treatment contrast imaging for precise treatment validation
Thermal dose
accumulation
MR thermometry
temperature feedback
© 2013 by Focused Ultrasound Foundation

5. Imaging of Uterine Fibroids
Ultrasound
MRI CT
© 2013 by Focused Ultrasound Foundation

6. Focused Ultrasound for Uterine Fibroids
© 2013 by Focused Ultrasound Foundation

7. The Procedure: Targeting
Structures
to be avoided
Region to be treated
© 2013 by Focused Ultrasound Foundation

8. The Procedure: Planning
© 2013 by Focused Ultrasound Foundation

9. The Procedure: Treatment
Temperature
measurement
Two sonication methods
Point by point or volumetric
© 2013 by Focused Ultrasound Foundation

10. The Procedure: Guidance
Move to
next target
© 2013 by Focused Ultrasound Foundation

11. The Procedure: Confirmation
Pre treatment
Treatment plan
Post treatment
© 2013 by Focused Ultrasound Foundation

12. Evolution of Technology
Initially in the 2004 Approval, FDA only allowed 30% of fibroid volume to be treated
No treatment limits now
Technology advancements allow
Larger fibroids*
Treatment envelope for deeper fibroids
300+% improvement in treatment time over 10 years
Initial rate of 20+ mL/hr
Current rate 80+ mL/hr
*Y. S. Kim, J. H. Kim, H. Rhim, H. K. Lim, B. Keserci, D. S. Bae, B. G. Kim, J. W. Lee, T. J. Kim, and C. H. Choi, “Volumetric MR-guided high-intensity focused ultrasound ablation with a one-layer strategy to treat large uterine fibroids: initial clinical outcomes,” Radiology, vol. 263, no. 2, pp. 600–609, May 2012.
© 2013 by Focused Ultrasound Foundation

13. Current State of Technology
Two MR guided device manufacturers
About 10,000 patients treated worldwide
Widespread regulatory approval
Very spotty reimbursement
155 publications on the use of Focused Ultrasound for uterine fibroid therapy
Promising results for use in patients
Seeking to improve fertility outcomes in patients with uterine fibroids
Adenomyosis
Sonalleve MR-HIFU*
*For investigational use only
© 2013 by Focused Ultrasound Foundation

14. General Screening Guidelines
Symptomatic fibroids
Pre- or peri-menopausal women
Symptoms are bulk, pain or bleeding
Pre-screening shows no pregnancy, malignancy or pelvic disease
Screening US for diagnosis of fibroids and confirmed limited-to-no calcifications
© 2013 by Focused Ultrasound Foundation

15. Pre-Treatment MRI
Precise determination of size, location, number of fibroids
Characterization of fibroid for treatment strategy
Viability for Focused Ultrasound therapy
Degree of vascularity (as assessed by perfusion with MRI)
Identify calcifications
Adenomyosis
Malignancy screening
Including suspicion of endometrial cancer and/or sarcoma
© 2013 by Focused Ultrasound Foundation

16. Relative Contraindication Absolute Contraindication
Patient Selection
Indication
Symptomatic
Bleeding
Pressure, pain
Pre- or peri-menopausal
Uterus size approx. 24 weeks gestation
Relative Contraindication
Morbidly obese or BMI ≥40
Degenerated fibroid
Extensive scarring over beam path
Desire for future pregnancy
Bowels interfering with beam path
Absolute Contraindication
Currently pregnant
MRI contraindication
Calcified or dominantly degenerated
© 2013 by Focused Ultrasound Foundation

17. Treating Multiple Fibroids
© 2013 by Focused Ultrasound Foundation

18. Symptom Relief After FUS Treatment
MR-Guided Focused Ultrasound of Uterine Leiomyomas: Review of a 12-month Outcome of 130 Clinical Patients
Retrospective study of women treated at Mayo Clinic from
Mean tumor load per patient cm3 (± 307.2)
Mean non-perfused volume immediately after treatment 45.4% (±22.5)
Gorny KR, Woodrum DA et al. Magnetic resonance–guided focused ultrasound of uterine leiomyomas: review of a 12-month outcome of 130 clinical patients. J Vasc Interv Radiol 2011
© 2013 by Focused Ultrasound Foundation

19. Symptom Relief After FUS Treatment
In normal commercial use, over 85% of patients experience sustained improvement in symptoms
Months post-procedure
Patients available for follow-up
Symptom improvement
Improved
No relief
Worse 3
105 90
(85.7%)
14 (13.3%)
1 (1%) 6 99 92
(92.9%)
7 (7.1%) 12
additional treatments
counted as ‘no relief’ = 89
78 (87.6%)
11 (12.4%)
Gorny KR, Woodrum DA et al. Magnetic resonance–guided focused ultrasound of uterine leiomyomas: review of a 12-month outcome of 130 clinical patients. J Vasc Interv Radiol 2011
© 2013 by Focused Ultrasound Foundation

20. Non Perfused Volume (NPV) Indicator of Treatment Durability*
The higher the NPV the lower the likelihood of retreatment
NPV increasing with learning curve and improved techniques
At NPV of 60% need for retreatment is similar to UAE and myomectomy
Add bar graph
*Stewart et al. Obstet Gynecol 2007-Av. NPV ratio 21.9% (N=359). Okada et al. Ultrasound in Obstet Gynecol 2009-Av. NPV ratio 46.6% (N=287) Leblang et al. AJR Av. NPV ratio 55% (N=80).Matzko 2nd MRgFUS Symposium Av. NPV ratio 59.1% (N=41),Matzko 1st European MRgFUS Symposium 2011 Av NPV- 67%
© 2013 by Focused Ultrasound Foundation

21. Durability Versus Other Uterine Preserving Treatments
References:
Subramanian S, Clark MA, Isaacson K. Outcome and resource use associated with myomectomy. Obs & Gyn.2001; 98:
Nezhat FR, Roemisch M, et al. Recurrence rate after laparoscopic myomectomy. Am Assoc Gynecol Laparosc. 1998;5:
Rossseti et al. Long term results of laparoscopic myomectomy: recurrence rate in comparison with abdominal myomectomy. Hum Reprod. 2001:16:
Doridot et al. Recurrence of leiomyomata after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc. 2001;8:
Spies JB, Bruno J, et al. Long-term outcome of uterine artery embolization of leiomyomata. Obstet Gynecol. 2005; 106:
Goodwin SC, Spies JB, et al. Uterine artery embolization for treatment of leiomyomata: long-term outcomes from FIBROID registry. Obstet & Gynecol. 2008; 111: 22-32
Sharp HT. Assessment of new technology in the treatment of idiopathic menorrhagia and uterine leiomyomata. Obstet Gynecol. 2006;108: 990–1003
Stewart EA, Gostout B, Rabinovici J, et at. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet & Gynecol. 2007;110:
Morita Y, Ito N, Hikida H, Takeuchi S, Nakamura K, Ohashi H. Non-Invasive Magnetic Resonance Imaging Guided Focused Ultrasound Treatment for Uterine Fibroids – Early Experience, Eur J Obstet Gynecol Reprod. Biol., 2008, 139(2):
© 2013 by Focused Ultrasound Foundation

22. Relationship Between Fibroid Shrinkage and Symptoms
As fibroid volume shrinks, symptoms and quality of life improve
Baseline Months Months
QoL improvements and 50% fibroid shrinkage in 6 months
Courtesy of UMC Utrecht, The Netherlands
© 2013 by Focused Ultrasound Foundation

23. FUS Side Effects and Complications
Expected side-effects of FUS-therapy
Transitory
30% patients may experience nausea, vomiting, leg and buttock pain, abdominal tenderness
Less frequent, transitory
< 10% patients may experience swelling, abdominal cramping, vaginal bleeding, urinary difficulty
< 3% patients may experience first degree skin burns (skin redness) and general pelvic pain
Very rare complications (< 1% patients)
Second and third degree skin burns
Neuropathy < 0.1% (Taran 2009)
Injury to abdominal/pelvic organs < 0.1% (Taran 2009)
© 2013 by Focused Ultrasound Foundation

24. Ongoing Studies in the US
SOnalleve FIbroid Ablation (SOFIA) Study
Philips Sonalleve FDA pre-market approval
RCT, comparison to sham
224 patients
Conducted at St. Luke’s, Johns Hopkins, University of Chicago, University of Michigan, Vanderbilt, Sunnybrook Health Sciences Centre, Samsung Medical Center in Korea
ExAblate UF V2 System for the Treatment of Symptomatic Uterine Fibroids
Safety trial for the newer ExAblate for faster planning and treatment times, broader patient selection, and improved range of treatment
106 patients
Conducted at Stanford, Brigham and Women’s, University of Virginia
FIRSTT: Comparing MR-guided Focused Ultrasound to Uterine Artery Embolization for Uterine Fibroids
Randomized study
180 patients
Conducted at Mayo, Duke
© 2013 by Focused Ultrasound Foundation

25. FUS and Pregnancy Patients who desire future pregnancy
Semin Reprod Med 2010
© 2013 by Focused Ultrasound Foundation

26. Post FUS pregnancies Total number of pregnancies Mean age
Average months to conception
Total deliveries
- Of them vaginal
Elective pregnancy termination
Spontaneous abortions
Ongoing pregnancies
Unknown
Average baby weight at term delivery
117 36 9
64 (55%)
59%
10 (9%)
22 (19%)
9 (8%)
12 (10%)
7.21 lbs
J Rabinovici, MD 3RD FUSF Symposium Washington, 2012
NOTE: There have been no prospective clinical trials to evaluate outcomes among women who have undergone ExAblate therapy and subsequently become pregnant. Patients of childbearing age should be cautioned of potential any potential complications if they were to become pregnant following ExAblate procedure.
© 2013 by Focused Ultrasound Foundation

27. Laparoscopic Myomectomy
Deliveries after FUS
Vaginal delivery rates after MRgFUS (rather than C-section) are more similar to those of general population
May result in fewer preterm deliveries and lower cost care for premature babies, than those of other treatments
Complication
General Population
UF Patients
UAE
Laparoscopic Myomectomy
MRgFUS
Cesarean Delivery
22%
48.5%
66%
77.8%
36%
Preterm Delivery
5-10%
16%
14%
7.4% 5%
References: J. Goldberg and Leonardo Pereira. Pregnancy outcomes following treatment for fibroids: uterine fibroid embolization versus laparoscopic myomectomy, Obstetrics and Gynecology 2006, 18:402–4 H. Homer, E. Saridogan, Uterine artery embolization for fibroids is associated with an increased risk of miscarriage, Fertility and Sterility J. Rabinovici et al. Pregnancy outcome after magnetic resonance–guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids, Fertility and Sterility Miller CE. Unmet Therapeutic Needs for Uterine Myomas. J Minimally Invasive Gynecol. 2009;16: 27
Caution: Investigational Device. Limited by United States Law to Investigational Use.
© 2013 by Focused Ultrasound Foundation 27

28. Pregnancy after FUS
41 yo. Nulligravida with 3 previous IVFs (the last one with oocytes from donor)
Previous myomectomy
Treated September 2010
Intramural fibroid
Treatment volume of 130, NPV 80%
Pregnancy: 7 months after treatment (frozen embryo transference)
Courtesy of H. Millan, MD, Instituto Cartuja, Seville, Spain
© 2013 by Focused Ultrasound Foundation

29. FUS In Spectrum of Treatment Options
Myomectomy
Patient population: intramural and subserosal uterine fibroids. Patients (Myomectomy) who want to become pregnant and who do not have contraindications for surgery
Disadvantages/Risks: Surgical risks and perioperative morbidity, adhesion risk and complications
Future Fertility: Yes, for Myomectomy only. Known risks shown in pregnancy post-procedure
Uterine fibroid embolization
Patient population: fibroids that are not subserous, submucosal or pedunculated. Wish to preserve uterus but are not interested in future fertility
Disadvantages/Risks: Possible surgical risks of infection and bleeding.
Future Fertility: Not recommended. 12% risk of placental abnormalities. Risk of ovarian failure, amenorrhea reported in <15%
Focused Ultrasound
Patient population: patients with symptomatic (<5 fibroids, range of sizes). Wish to preserve uterus and may/may not be family complete
Disadvantages/Risks: Limits on types and location of fibroids that can be accessed. Risks of abdominal pain, transient lower leg or back pain, vaginal discharge or bleeding, fever skin burns.
Future Fertility: Reports of deliveries. Risks are not yet fully defined, in several reports there is an indication MR-HIFU may improve fertility.
© 2013 by Focused Ultrasound Foundation

30. Focused Ultrasound Meets Patient Needs
Non-invasive low pain alternative to surgery
Out-patient procedure Go home the same day
Quick recovery: Return
to normal activity in 2 days
Uterus preserving therapy Option for future pregnancy
*Source: AHRQ Publication No. 07-E011: Management of Uterine Fibroids: An Update of the Evidence.
© 2013 by Focused Ultrasound Foundation

31. Meeting Patient Needs: The Potential Value for Patients
% rating treatment their top choice
BASE: ALL QUALIFIED RESPONDENTS (n*=968) *base varies slightly
Q960 Please rank the following treatment options where “1” = your top choice and “6” = your bottom choice.
© 2013 by Focused Ultrasound Foundation

32. Practice Building with Fibroid Center and Focused Ultrasound53 27 4 16 10 15 20 2 6 11 42 22 18 12 7 8 40 60 80
100
120
140
2003
2004
2005
2006 LM LH AM AH
MRgFUS
117
102 50
# of UF patients
Case study: UF treatments at Shin-Suma Kobe, Japan
Halo effect of cutting edge technology
GYNs central to treatment team
Offering of complete range of treatments for women, specifically a non-invasive, low morbidity option
Drive increase in practice volume
Before FUS
1 year after FUS
2 years after FUS
3 years after FUS
Legend:
LM Laparoscopic Myomectomy
LH Laparoscopic Hysterectomy
AM Abdominal Myomectomy
AH Abdominal Hysterectomy
MRgFUS MR guided Focused Ultrasound
© 2013 by Focused Ultrasound Foundation