Enhanced MR guided Focused Ultrasound Surgery (MRgFUS) Guidelines Demonstrates Improved Efficacy and Durability for the Treatment of Uterine Myoma

Phyllis J. Gee, M.D., FACOGNorth Texas Uterine Fibroid Institute, Plano, Texas

Presented at ACOG's 2007 Annual Clinical Meeting (ACM) San Diego, CA, May 5-9, 2007

Purpose

Results

Conclusions

Background

Brigham and Women’s Hospital, John Hopkins Hospital, Mayo Clinic, Lahey Clinic, Radnet, North Texas Uterine Fibroid Institute, Sightline-Houston, University MRI, Virtua Hospital

The purpose of this multi-center study trial is to compare the clinical outcomes of MRgFUS patients treated using expanded and commercial treatment guidelines with those patients treated using the pivotal treatment guidelines. Data were collected to confirm improved safety and efficacy of MRgFUS treatment of uterine leiomyoma with these expanded guidelines.

Hypothesis1.Expanded and commercial treatment guidelines allow more efficacious treatments that are

durable (greater symptom relief) with as good a safety profile as the pivotal treatment guidelines. 2.Secondary outcomes included the relationship between symptom severity score (SSS)

improvement versus non-perfused leiomyoma volume and the percentage of patients requiring alternative treatments post-MRgFUS.

– Similar to how a magnifying glass focuses light energy, ultrasound can be focused to a spot the size of a jelly bean.

– The high energy density at the focus results in tissue heating and thermal injury.

– As depicted below: During MRgFUS treatment, the physician uses MR images to aid in planning treatment location (1), visualizing where the ultrasound will be delivered (2), monitoring temperature changes inside the body (3), and evaluating the treatment outcome (4).

Water Bath

Focused Ultrasound

Beam

Tumor

Transducer

MR Guided…- Real Time 3D imaging- MRI Thermal monitoring

Methods

1 2

3 4

Pivotal Study Guidelines Expanded Tx Guidelines Commercial Guidelines

Volume restriction as a percentage of fibroid

Prescribed volume limited to 33% of all fibroids

Treated Vol. limited to 50% of all fibroids except submucosal - 33%

Treated volume limited to 50% of all fibroids

Volume restriction Max Tx of 100 cc per fibroid or 150 cc if more

than 1 Fibroid

Max Tx 150 cc regardless of number of treatments

None

Time restriction first to last sonication

120 minutes 180 minutes 180 minutes

Minimum distance to the endometrium

1.5 cm None None

Minimum distance to the serosa

1.5 cm 1.5 cm 1.5 cm

Restricted distance to fibroid capsule

0.5 cm on side closest to serosa

None None

Second treatment session

No Yes – limited to 2 within a 2 week period

Yes – limited to 2 within a 2 week period

Group AGroup C

Group B

Limited Tx Volume Expanded Tx Volume

Treatment Guidelines and Patient Population

Symptom Severity Score (SSS)

- a validated tool to compare symptom severity among women suffering from uterine leiomyoma- MRgFUS patients in the study were highly symptomatic and had a much greater SSS than an average patient with uterine leiomyoma

Group A patients: Pivotal study guidelines

Group B patients: Expanded treatment guidelines

Group C patients: Commercial treatment guidelines

UF005-B1 Continued access study group 1 patients N= 96

UF005-B2 Continued access study group 2 patients N= 64

UF014 African American study patients N= 73

77%

71%

84%

75%71% 71%

86%

76%74%

76%

91%

86%85% 85%86%

90%

86%

3 Month 6 Month 12 Month 24 Month 36 Month

Months Post ExAblate Tx

UF002 UF005-B1 UF005-B2 UF014 • Symptom improvement was greatest under commercial treatment guidelines.• 86% of patients treated with commercial treatment guidelines sustained a 10-point or greater improvement in SSS by 12 months compared to 84% of patients treated with expanded guidelines and 71% of patients treated with pivotal guidelines.•84% of all patients had some form of symptom improvement

Percent of patients exhibiting >10 points SSS improvement

• Expanded and commercial treatment guidelines (UF005-B2 and UF014) resulted in greater reduction in symptom severity score at 3,6,12 and 24 months• Majority of symptom relief was experienced at 3 months (first data point)• Durable / sustained symptom relief up to 36 months

Reduction in Patient Symptoms Over Time

20

30

40

50

60

70

0 6 12 18 24 30 36

Months Post-Tx

Me

an

SS

S

UF002

UF005-B1

UF005-B2

UF014

4%5%

1%

6%

17%20%

27%

8%

39%

28%

22%

10%

30%

45%

25%

UF002 UF005-B1 UF005-B2 UF014

Patient Group

Month-6Month-12Month-24Month-36

• Patients treated under the expanded and commercial treatment guidelines (UF005-B2 and UF014) required fewer alternative treatments than those treated under the pivotal study guidelines.

Rate of Alternative Treatments

This data confirms improved efficacy and durability of MR-guided Focused Ultrasound Surgery of uterine leiomyoma with expanded commercial guidelines. These enhanced treatments result in greater symptom relief and less need for alternative treatments.

References

1.Stewart, E.A., et al. “Clinical Outcomes of Focused Ultrasound Surgery for the Treatment of Uterine Fibroids.” Fertility and Sterility 2006;85 (1):22-29.2.Spies, J. B., Coyne, K., et.al. “The UFS-QOL, A New Disease-specific Symptom and Health-related Quality of Life Questionnaire for Leiomyomata. Obstet Gynecol 2002; 99(2):290-300

Participating Sites

Average Symptom Severity Score

22.5

44

62

0

20

40

60

80

Women withoutfibroids

Women withfibroids

Women enrolledin pivotal study

UFS-QOLValidation Study

Objective: Data were collected to confirm improved efficacy of Magnetic Resonance-guided focused ultrasound surgery (MRgFUS) treatment of uterine leiomyomata with expanded guidelines. Methods: From April 2003 to March 2006, 160 patients were treated in a continued access study (UF005), and 73 were treated in a study involving African-American patients exclusively (UF014). MRgFUS was performed using three different sets of treatment guidelines: 96 patients in UF005 were treated under pivotal study guidelines with limited treatment times and volumes (Group A), 64 patients in UF005 were treated with expanded guidelines (Group B), and the UF014 patients were treated using current commercial treatment guidelines (Group C). Results: Outcomes confirmed that patients treated under expanded and commercial treatment guidelines achieved greater nonperfused myoma volumes and greater symptom relief than those treated under the pivotal study guidelines. The symptom severity score, a component of the validated uterine leiomyoma quality of life questionnaire, was used to quantify these results. Approximately 85% of Group B patients achieved a greater than 10-point improvement in symptom severity score compared with 74% of Group A patients, which represents a 15% improvement in results. The number of alternative treatments for Group B patients at 12 and 24 months was also much less than that for Group A patients. Of the Group C patients, 43 have crossed the 3-month follow-up. Ninety-three percent (93%) of these patients have achieved symptom severity score improvement of 10 points or greater. Conclusions: These findings demonstrate that larger leiomyoma treatment volumes result in larger nonperfused tumor volumes after MR-guided focused ultrasound surgery. These enhanced treatments result in greater symptom relief and less need for alternative treatment.

MRgFUS is a non-invasive outpatient treatment for uterine leiomyoma that enables women to go home immediately, returning to normal activities and to work within 1-2 days

Abstract