BlueCross and BlueShield of Montana Medical Policy/Codes
Magnetic Resonance Imaging-Guided High Intensity Focused Ultrasound (MRgFUS) Ablation of Uterine Fibroids and Other Tumors
Chapter: Radiology
Current Effective Date: August 27, 2013
Original Effective Date: November 01, 2012
Publish Date: August 27, 2013
Revised Dates: July 29, 2013
Description

Uterine fibroids (leiomyomata) are one of the most common conditions affecting women in the reproductive years; symptoms include menorrhagia, pelvic pressure, or pain. There are several approaches that are currently available to treat symptomatic uterine fibroids: hysterectomy; abdominal myomectomy; laparoscopic and hysteroscopic myomectomy; hormone therapy; uterine artery embolization; and watchful waiting. Hysterectomy and various myomectomy procedures are considered the gold standard treatment.

Recently, there has been interest in using high-intensity focused ultrasound (HIFU) treatment that is guided by magnetic resonance imaging (MRI; MRgFUS) as a totally noninvasive approach to the ablation of uterine fibroids. The ultrasound beam penetrates through the soft tissues and, using MRI for guidance and monitoring, the beam can be focused on targeted sites. The ultrasound causes a local increase in temperature in the target tissue, resulting in coagulation necrosis while sparing the surrounding normal structures. The ultrasound waves from each sonication can be focused into a maximum tissue volume of 4.3 cm3, causing a rapid rise in temperature sufficient to achieve tissue ablation at the focal point. In addition to providing guidance, the associated MRI can provide on-line thermometric imaging that provides a temperature “map” that can further confirm the therapeutic effect of the ablation treatment and allow for real-time adjustment of the treatment parameters.

The ultrasound equipment is specially designed to be compatible with MR magnets and is integrated into standard clinical MRI units. The ExAblate® System (InSightec, Inc., Dallas, TX) consists of a focused piezoelectric phased-array transducer, a computer-controlled positioning system, and a multichannel radiofrequency amplifier system. The array is located within a specially designed table in a water bath; imaging is performed with a custom receive-only pelvic coil. The ExAblate® System has received U.S. Food and Drug Administration (FDA) approval for treatment of uterine fibroids. MRI-guided high-intensity focused ultrasound ablation of other tumors, including breast, prostate, and brain tumors and for the treatment of tumors metastatic to bone for the palliation of pain is also being studied. However, the device approved by the FDA for MRI-guided ultrasound ablation is only for uterine fibroids.

Regulatory Status

In October 2004, the FDA approved the ExAblate® 2000 System (via the premarket application [PMA] process) for “ablation of uterine fibroid tissue in pre- or perimenopausal women with symptomatic uterine fibroids who desire a uterine sparing procedure.” Treatment is indicated for women with a uterine gestational size of less than 24 weeks who have completed childbearing. In December 2009, the ExAblate® 2100 System received premarket approval. It includes several modifications to the previous system including enhanced sonication and a detachable cradle. Approval remains limited to treatment of symptomatic uterine fibroids and is also indicated in women with a uterine size of less than 24 weeks and those who have completed child bearing.

Policy

Investigational

Blue Cross Blue Shield of Montana (BCBSMT) considers magnetic resonance imaging-guided high intensity focused ultrasound (MRgFUS) ablation of tumors experimental, investigational and unproven, including but not limited to:

  • Uterine fibroids,
  • Breast tumors,
  • Brain tumors,
  • Prostate tumors,
  • Palliative treatment of bone metastasis.

Rationale

In June 2005, Blue Cross Blue Shield Association (BCBSA) published a Technology Evaluation Center (TEC) Assessment on magnetic resonance imaging-guided high intensity focused ultrasound (MRgFUS) therapy for symptomatic uterine leiomyomata; this assessment found insufficient evidence of efficacy compared to the conventional therapies. (1) The following is a summary of the literature through June 2012.

Uterine Fibroids

No randomized controlled trials (RCTs) have been published using MRgFUS. There is one published non-randomized study comparing MRgFUS to another treatment for uterine fibroids; this is the “pivotal” study designed for FDA approval of the ExAblate® 2000 device. (2,3) The study included 109 women treated with MRgFUS and 83 women treated with abdominal hysterectomy. The primary outcome was change in the symptom severity score (SSS) that is part of the validated Uterine Fibroid Symptom Quality of Life. Symptom severity is measured by 8 questions relevant to bulk and bleeding symptoms; it is a 0–100 scale, with the higher number representing greater severity of symptoms. Outcome data were initially reported for the MRgFUS group only. At 6 months’ follow-up, 71% of the MRgFUS group achieved a 10-point or greater reduction in SSS, but this decreased to 51% at 12 months. It is unclear what represents a clinically meaningful change in SSS, the primary outcome measure. A threshold of greater than 10 points was selected for the analysis, but this is somewhat arbitrary and not substantiated by other research. Twenty-one percent of those treated by MRgFUS needed additional surgical treatment, and 4% underwent a repeat MRgFUS by 12 months.

In 2009, Taran and colleagues reported outcomes for the hysterectomy group. (4) The Taran article did not include the original primary outcome measure, SSS scores, and instead reported findings on a different quality of life measure, the SF-36; also reported were safety data. A significantly higher proportion of women in the hysterectomy group (82 of 83, 99%) reported at least one adverse event compared to women in the MRgFUS group (88 of 109, 81%). Pain or discomfort, adverse events associated with the gastrointestinal tract, dermatological system, nervous system, and cardiovascular system were significantly more common in the hysterectomy group. However, a similar proportion reported a serious adverse event, 9 of 109 (8%) in the MRgFUS group and 8 of 83 (10%) in the hysterectomy group. At 6 months, there were significantly higher scores in the hysterectomy group on 2 of 8 subscales on the SF-36; scores on the remaining subscales did not differ significantly between groups. The SF-36 scores were subject to a multiple comparison bias; a large number of statistical comparisons were done for secondary outcomes and p-values were not adjusted. Moreover, it was not clear why the original primary outcome, the SSS, was not reported.

Another non-randomized comparative study compared two variations on the MRgFUS procedure. (5) Patients were either treated with the original protocol (33% of fibroid volume with a maximum treatment time of 120 min, n=96) or modified protocol (50% treatment volume, 180 min maximum treatment time, and a second treatment if within a 14-day period, n=64). In the original group, the nonperfused (effectively treated) area was calculated at 17% of fibroid volume compared with 26% of fibroid volume with the modified protocol. Overall, symptom severity was reported to have decreased from a score of 62 at baseline to 33 at 12 months, with fewer patients in the modified group choosing alternative treatment (28% vs. 37%, respectively). Interpretation of these results was limited by 49% loss to follow-up; 55 patients (57%) from the original treatment protocol completed follow-up. Only 21 patients (33%) from the modified protocol group were evaluable at 12-month follow-up.

A 2007 publication reported 24-month follow-up from three Phase 3 trials and 1 postmarketing study (total of 416 patients). (6) The study found a relationship between the nonperfused volume ratio and the probability of undergoing additional leiomyoma treatment. For nonperfused volume ratios of 20% to 50%, there was a 25% probability of additional treatment. Patients with a nonperfused volume ratio of less than 20% of fibroid volume had a 40% probability of additional treatment. No shrinkage (and a trend toward growth) was seen with nonperfused volume ratios of 10% or less. Most women were found to have had limited treatments, with 57% of the patients having a nonperfused volume of 20% or less and 34% of the patients having a nonperfused volume between 30% and 70%. Fewer than 3% of women had a nonperfused volume ratio of 70% or greater. These results raise questions about the amount of nonperfusion achieved with current treatment protocols.

Several case series have reported on the efficacy and safety of MRgFUS for treating uterine fibroids. For example, a 2011 case series included 40 women who were treated with MRgFUS for symptomatic uterine fibroids at one center in the U.S. (7) The primary study endpoints were change from baseline in quality of life (QOL) and symptom severity. (Higher scores on the quality of life measure and lower scores on the symptom severity measure indicated improvement). Twenty-nine of the 40 (73%) patients completed the three-year follow-up. The mean symptom severity score was 64.8 at baseline and 17.0 at 3 years; this represents a mean reduction of 47.8 points. The mean baseline QOL score was 44.1 and the mean QOL at the 3-year follow-up was 83.9, a mean increase of 39.8 points. The improvement from baseline to 3 years was statistically significant for both outcome variables; however, there is no control group with which to compare results. Another 2011 single-center case series reported 12-month outcome data on 130 women treated with MRgFUS. (8) Eight women had additional procedures to relieve symptoms within one-year of MRgFUS treatment; 7 underwent hysterectomy and 1 underwent endometrial ablation. Data on symptom relief at 12 months were available for 70 of 130 (54%) of patients. Fifty-one of the 70 (73%) reported excellent symptom relief. Conclusions about efficacy of MRgFUS cannot be drawn due to the lack of a comparison group and the large amount of missing data.

A prospective registry of pregnancies after MRgFUS had been maintained by the manufacturer of the ExAblate device. A 2010 article reported that there were 54 known pregnancies a mean of 8 months after treatment. (9) They included 8 pregnancies from clinical trials designed for women who did not desire pregnancy, 26 pregnancies after commercial treatment, and 20 pregnancies in 17 patients from an ongoing study of MRgFUS in women trying to conceive. Twenty-two of the 54 pregnancies (42%) resulted in deliveries, 11 were ongoing beyond 20 weeks at the time the article was written. There were 14 miscarriages (26%) and 7 elective terminations (13%). Among the 22 live births, the mean birth weight of live births was 3.3 kg, and the vaginal delivery rate was 64%. The article provides initial information on the impact of MRgFUS for uterine fibroids on pregnancy; findings suggest that fertility may be maintained but that the number of cases is too small to draw definitive conclusions. Moreover, the study does not address the possible impact of MRgFUS treatment on the ability to become pregnant.

Other Tumors

A 2011 review article on MRgFUS as an oncologic treatment stated, “Although the potential applications of MRgFUS in oncology are very promising, further studies of feasibility and tolerability are needed for different anatomical districts. Phase III studies are needed as soon as possible in order to make direct comparisons of MRgFUS with surgery and radiotherapy.” (10)

Breast Tumors

No controlled studies evaluating MRgFUS for treating breast cancer have been published. The published literature is limited to small case series (i.e., including fewer than 20 patients each). (11-14)

Brain Cancer

One article reported on initial findings in 3 patients. (15) The authors report that it was possible to focus an ultrasound beam into the brain transcranially, and they believe that thermal ablation without overheating the brain is possible; however, substantial technical barriers to using MRgFUS for treating brain tumors remain.

Palliative Treatment of Bone Metastases

No controlled studies evaluating MRgFUS for palliative treatment of bone metastases have been published. One RCT comparing MRgFUS to sham treatment is underway (see section on ongoing clinical trials, below). Several manufacturer-sponsored case series have been published. In 2009, Liberman and colleagues published findings of a multicenter prospective study conducted in Canada, Israel, and Germany. (16) The study included 31 patients who had painful bone metastases who had failed or refused other treatment options; 25 patients (81%) were available for 3-month follow-up. (18) The mean VAS score decreased from 5.9 before treatment to 1.8 three months after treatment. Thirteen of 25 patients who used non-opioid analgesics and 6 of 10 who used opioids decreased medication use after treatment. Neither series reported any treatment-related adverse effects.

Ongoing clinical trials

The FIRSST: Comparing MRgFUS (MR guided Focused Ultrasound) versus UAE (Uterine Artery Embolization) (NCT00995878) (17): This is a randomized controlled trial comparing MRgFUS to UAE in pre-menopausal women at least 25 years of age who have symptomatic uterine fibroids. The study is sponsored by the Mayo Clinic.

ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Metastatic Bone Tumors for the Palliation of Pain (NCT00656305) (18): This randomized controlled trial is comparing Exablate treatment to sham treatment. It includes patients with symptomatic bone metastases or multiple myeloma bone lesions who are not candidates for radiation therapy. December 2011 was listed as the final data collection date for the primary outcome measure.

Practice Guidelines and Position Statements

Agency for Healthcare Research and Quality (AHRQ): A 2007 technology assessment on the management of uterine fibroids concluded that the strength of the evidence about MRgFUS is weak. (19)

A search of the National Guideline Clearinghouse database did not identify any practice guidelines that included recommendations on MRgFUS for treating uterine fibroids or other conditions.

Summary

MRIgFUS treatment is FDA-approved only for the treatment of uterine fibroids. To date, there are no randomized controlled trials and only one non-randomized study comparing MRgFUS to a different treatment. Limitations of the published comparative study include lack of randomization, data on the comparison group were not published until 5 years after data on the treatment group, the clinical significance of the primary outcome was unclear, and there were no follow-up data beyond 1 year. There is insufficient evidence on the long-term treatment effects, recurrence rates, and impact on future fertility and pregnancy. Thus, MRgFUS is considered experimental, investigational and unproven for treatment of uterine fibroids.

MRgFUS is being investigated for use in several applications that are not currently approved by the FDA. There are some small published case series but no comparative studies have been published. One RCT comparing MRgFUS to sham treatment as palliative therapy in patients with symptomatic bone metastases is underway. Due to a lack of regulatory approval and insufficient evidence of the impact on health outcomes, MRgFUS is considered experimental, investigational and unproven for treatment of other benign and malignant tumors.

Coding

Disclaimer for coding information on Medical Policies          

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

Rationale for Benefit Administration
 
ICD-9 Codes

Experimental, investigational and unproven for all codes.

ICD-10 Codes

Experimental, investigational and unproven for all codes.

Procedural Codes: 0071T, 0072T
References
  1. Blue Cross Blue Shield Association Technology Evaluation Center (TEC). Magnetic resonance-guided focused ultrasound therapy for symptomatic uterine fibroids. TEC Assessments 2005: Volume 20, Tab 10.
  2. Hindley J, Gedroyc WM, Regan L et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol 2004; 183(6):1713-9.
  3. Stewart EA, Rabinovici J, Tempany CM et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril 2006; 85(1):22-9.
  4. Taran FA, Tempany CM, Regan L et al. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol 2009; 34(5):572-8.
  5. Fennessy FM, Tempany CM, McDannold NJ et al. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology 2007; 243(3):885-93.
  6. Stewart EA, Gostout B, Rabinovici J et al. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol 2007; 110(2 pt 1):279-87.
  7. Kim HS, Baik JH, Pham LD et al. MR-guided high-intensity focused ultrasound treatment for symptomatic uterine leiomyomata: long-term outcomes. Acad Radiol 2011; 18(8):970-6.
  8. Gorny KR, Woodrum DA, Brown DL 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; 22(6):857-64.
  9. Rabinovici J, David M, Fukunishi H et al. Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil Steril Fertil Steril 2010; 93(1):199-209.
  10. Alongi F, Russo G, Spinelli A et al. Can magnetic resonance image-guided focused ultrasound replace local oncology treatments? A review. Tumori 2011; 97(3):259-64.
  11. Zippel DB, Papa MZ. The use of MR imaging guided focused ultrasound in breast cancer patients; a preliminary phase one study and review. Breast Cancer 2005; 12(1):32-8.
  12. Hynynen K, Pomeroy O, Smith DN et al. MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study. Radiology 2001; 219(1):176-84.
  13. Gianfelice D, Khiat A, Amara M et al. MR imaging-guided focused US ablation of breast cancer: histopathologic assessment of effectiveness – initial experience. Radiology 2003; 227(3):849-55.
  14. Gianfelice D, Khiat A, Amara M et al. MR imaging-guided focused ultrasound surgery of breast cancer: correlation of dynamic contrast-enhanced MRI with histopathologic findings. Breast Cancer Res Treat 2003; 82(2):93-101.
  15. McDannold N, Clement GT, Black P et al. Transcranial magnetic imaging-guided focused ultrasound surgery of brain tumors: initial findings in 3 patients. Neurosurgery 2010; 66(2):323-32.
  16. Liberman B, Gianfelice D, Inbar Y et al. Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study. Ann Surg Oncol 2009; 16(1):140-6.
  17. The FIRSST: Comparing MRgFUS (MR guided Focused Ultrasound) versus UAE (Uterine Artery Embolization) (NCT00995878). Last updated November 22, 2011. Available online at: www.ClinicalTrials.gov . Last accessed January 2012.
  18. ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Metastatic Bone Tumors for the Palliation of Pain. (NCT00656305). Sponsored by Insightec. Last updated October 31, 2011. Available online at: www.ClinicalTrials.gov . Last accessed January 2012.
  19. Viswanathan M, Hartmann K, McKoy N et al. Management of uterine fibroids: an update of the evidence. Evidence Report/Technology Assessment No. 154 (Prepared by RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-02-0016. AHRQ Publication No. 07-E011. Rockville, MD: Agency for Healthcare Research and Quality. July 2007. Available online at: www.ahrq.gov . Last accessed January 2012.
  20. MRI-Guided Focused Ultrasound (MRgFUS) for the Treatment of Uterine Fibroids and Other Tumors.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (February 2012) Surgery 7.01.109.
History
July 2012 New Policy for BCBSMT: Policy added with literature review through December 2011. Policyt statement is investigational
August 2013 Policy formatting and language revised.  Policy statement unchanged.  Title changed from "MRI-Guided Focused Ultrasound (MRgFUS) for the Treatment of Uterine Fibroids and Other Tumors" to "Magnetic Resonance Imaging-Guided High Intensity Focused Ultrasound (MRgFUS) Ablation of Uterine Fibroids and Other Tumors".
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Magnetic Resonance Imaging-Guided High Intensity Focused Ultrasound (MRgFUS) Ablation of Uterine Fibroids and Other Tumors