Coverage Policy Manual
Policy #: 2004026
Category: Surgery
Initiated: July 2004
Last Review: August 2022
  MR Guided Ultrasound Ablation - Uterine Fibroids and Other Tumors

Description:
An integrated system providing magnetic resonance guided focused ultrasound (MRgFUS) treatment is proposed as a noninvasive therapy for uterine fibroids and for pain palliation of bone metastases. MRgFUS is also being investigated for the treatment of other benign and malignant tumors as well as essential tumors.
 
Uterine fibroids are one of the most common conditions affecting women in the reproductive years. African American women have a greater lifetime incidence of uterine fibroids compared to other racial groups (Eltoukhi, 2014). Symptoms of uterine fibroids include menorrhagia, pelvic pressure, or pain.
 
Approaches currently available to treat symptomatic uterine fibroids include hysterectomy, abdominal myomectomy, laparoscopic and hysteroscopic myomectomy, hormone therapy, uterine artery embolization, and watchful waiting. Hysterectomy and various myomectomy procedures are considered the criterion standard treatments.
 
Metastatic bone disease is one of the most common causes of cancer pain.
 
Existing treatments include conservative measures (e.g., massage, exercise) and pharmacologic agents (e.g., analgesics, bisphosphonates, corticosteroids). For patients who do not respond to these treatments, standard care is external-beam radiotherapy. However, a substantial proportion of patients have residual pain after radiotherapy, and there is a need for alternative treatments for these patients.
 
Essential tremor (ET) is the most common movement disorder, with an estimated prevalence of 5% worldwide. Essential tremor most often affects the hands and arms, may affect head and voice, and rarely includes the face, legs, and trunk. Essential tremor is heterogeneous among patients, varying in frequency, amplitude, causes of exacerbation, and association with other neurologic deficits.
 
The neuropathology of ET is uncertain, with some evidence suggesting that ET is localized in the brainstem and cerebellum. If patients with ET experience intermittent or persistent disability due to the tremors, initial therapy is with drugs (beta-blockers or anticonvulsants). For medicine-refractory patients, surgery (deep brain stimulation or thalamotomy) may be offered, though high rates of adverse events have been observed.
 
The 3 cardinal features of Parkinson disease (PD) are tremor, bradykinesia, and rigidity. The tremor in PD is a resting tremor that occurs when the body part is not engaged in purposeful activities. Major subtypes of PD include tremor-dominant, akinetic-rigid, and postural instability and gait difficulty. The progression of PD is highly variable and patients can change subtypes as the disease progresses.
 
Dopaminergic therapy (ie, levodopa or a dopamine agonist) is the first-line treatment for PD, which improves tremor. Amantadine and anticholinergics (eg, trihexyphenidyl) can also be considered as initial treatment for tremor-dominant PD or as add-on therapy in patients who have persistent tremor despite dopaminergic therapy. For medication-refractory patients, surgery (deep brain stimulation or lesioning procedures) may be offered. Lesioning procedures include conventional unilateral thalamotomy and focused ultrasound thalamotomy. Deep brain stimulation is the most frequently performed surgical procedure for the treatment of PD.
 
Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive treatment that combined 2 technologies, focused ultrasound and magnetic resonance imaging (MRI). 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 are focused at a focal point which has a maximum focal volume of 20 nm in diameter and 15 nm in height/length. This causes a rapid rise in temperature (i.e., to approximately 65°C to 85°C), which is 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 U.S. Food and Drug Administration (FDA) has approved the ExAblate® MRgFUS system (InSightec, Inc., Haifa, Israel) for 4 indications: treatment of uterine fibroids (leiomyomata), palliation of pain associated with tumors metastatic to bone, medication refractory ET, and tremor-dominant PD. The ultrasound equipment is specially designed to be compatible with MR magnets and is integrated into standard clinical MRI units. It includes a patient table, which includes a cradle housing the focused ultrasound transducer in a water or light oil bath. Some models of the device have a detachable cradle; only certain cradle types can be used for palliation of pain associated with metastatic bone cancer. For treating pain associated with bone metastases, the aim of MRgFUS is to destroy nerves in the bone surface surrounding the tumor.
 
MRgFUS is also being investigated for the treatment of other tumors, including breast, prostate, brain, and desmoid tumors as well as nonspinal osteoid osteoma.
 
Regulatory Status
In October 2004, the U.S. Food and Drug Administration (FDA) approved via the premarket application (PMA) process, the ExAblate® 2000 System (Insightec, Inc., Haifa, Israel) 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 October 2012, the FDA approved the ExAblate® System, Model 2000/2100/2100 VI via the PMA process. The intended use of the device is for pain palliation in adult patients with metastatic bone cancer who failed or are not candidates for radiation therapy. The device was evaluated through an expedited review process. The FDA required a post-approval study with 70 patients to evaluate the effectiveness of the system under actual clinical conditions.
 
In July 2016, the FDA approved the use of the ExAblate Neuro System for the treatment of ET in patients who have not responded to medication (beta-blockers or anticonvulsant drugs) through the premarket approval process. In December 2018, the FDA approved the use of the ExAblate Model 4000 (Neuro) for the treatment of tremor-dominant PD with medication-refractory tremor through the premarket approval process.
 
FDA product codes: NRZ, POH.
 
Coding
MRI-guided high-intensity ultrasound ablation of uterine fibroids is specifically identified by the following category III CPT codes:
 
0071T: Focused ultrasound ablation of uterine leiomyomata, including MR guidance; total leiomyomata volume of less than 200 cc of tissue
 
0072T: As above, but with total leiomyomata volume greater or equal to 200 cc of tissue
 
These CPT codes should not be used in conjunction with 51702 (insertion of temporary indwelling bladder catheter, simple) or 77022 (magnetic resonance imaging guidance for, and monitoring of, visceral tissue ablation).

Policy/
Coverage:
Effective July 2021
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Magnetic resonanceguided high-intensity ultrasound ablation for pain palliation in adults with metastatic bone cancer who have failed or are not candidates for radiotherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Magnetic resonanceguided high-intensity ultrasound ablation for the treatment of medicine-refractory essential tremors meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Magnetic resonance-guided high intensity ultrasound ablation does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in all other situations including but not limited to:
        • Treatment of uterine fibroids  
        • Treatment of other tumors (eg, brain cancer, prostate cancer, breast cancer, desmoid)
        • Treatment of medication-refractory tremor dominant Parkinson disease
 
For contracts without primary coverage criteria, magnetic resonance-guided high intensity ultrasound ablation is considered investigational in all other situations including but not limited to:
 
        • Treatment of uterine fibroids  
        • Treatment of other tumors (eg, brain cancer, prostate cancer, breast cancer, desmoid)
        • Treatment of medication-refractory tremor dominant Parkinson disease
 
Investigational services are specific contract exclusions in the member certificate of coverage.
 
Effective Prior to July 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Magnetic resonanceguided high-intensity ultrasound ablation for pain palliation in adults with metastatic bone cancer who have failed or are not candidates for radiotherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Magnetic resonanceguided high-intensity ultrasound ablation for the treatment of medicine-refractory essential tremors meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
MRI-guided high intensity ultrasound ablation does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in all other situations including but not limited to:
    • Treatment of uterine fibroids  
    • Treatment of other tumors (eg, brain cancer, prostate cancer, breast cancer, desmoid)
 
For contracts without primary coverage criteria, MRI-guided high intensity ultrasound ablation is considered investigational in all other situations including but not limited to:
 
    • Treatment of uterine fibroids  
    • Treatment of other tumors (eg, brain cancer, prostate cancer, breast cancer, desmoid)
 
Investigational services are specific contract exclusions in the member certificate of coverage.
 
Effective Prior to July 2018
 
MRI-guided high intensity ultrasound ablation of uterine fibroids does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. This treatment is currently being studied in a clinical trial.
 
For contracts without primary coverage criteria, MRI-guided high intensity ultrasound ablation of uterine fibroids is considered investigational.  Investigational services are specific contract exclusions in the member certificate of coverage.
 
MRI-guided high intensity ultrasound ablation of other tumors, including but not limited to breast, brain, prostate cancer, and palliative treatment of bone metastases does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For contracts without primary coverage criteria, MRI-guided high intensity ultrasound ablation of other tumors, including but not limited to breast, brain, prostate cancer, and palliative treatment of bone metastases is considered investigational.  Investigational services are specific contract exclusions in the member certificate of coverage.
 
Effective prior to April 2012
MRI-guided high intensity ultrasound ablation of uterine fibroids does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. This treatment is currently being studied in a clinical trial.
 
For contracts without primary coverage criteria, MRI-guided high intensity ultrasound ablation of uterine fibroids is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
There is minimal published data regarding MRI guided high intensity focused ultrasound ablation of uterine fibroids.  Stewart and colleagues reported the results of a case series of 55 women with symptomatic uterine fibroids who either underwent high intensity focused ultrasound treatment or who underwent a planned hysterectomy within one month after the ultrasound treatment.   In this latter group, hysterectomy specimens provided pathologic correlation of treatment.  Typically only one fibroid was targeted for treatment and no attempt was made to target the fibroid that was the most likely to cause symptoms.  Additionally, fibroids that would require the ultrasound beam to pass through bowel or bladder were excluded from treatment.  While the procedure was well tolerated, there was no attempt to assess mid or long term outcomes.  High intensity focused ultrasound has also been investigated as a treatment of breast fibroadenomas, prostate cancer and renal cancer.
 
2007 Update
In a review article Sharp commented :  “Outcomes of patients undergoing magnetic resonance-guided focused ultrasonography at 6 months and 12 months were reported from the FDA trial.  They followed 109 patients at 6 months and 82 patients at 12 months.  Although only modest volume reductions were noted, 13.5% at 6 months and 9.4% at 12 months using intention to treat analysis.  71% reached their target symptom reduction at 6 months and 51% at 12 months.  At 12 months 21% of women needed an alternative surgical therapy for leiomyomata...Long-term studies are needed to discern whether the minimally invasive advantage of this approach will lead to durable results.”  Other authors also indicated the need for longer-term follow-up.
 
A search of the MEDLINE database was performed for the period of August 2006 through September 2007. A technology assessment from the Agency for Healthcare Research and Quality (AHRQ) on the management of uterine fibroids was published.  Their literature search was completed in August 2006 and evaluated the same studies reviewed above. The AHRQ report concluded that the strength of the evidence about MRgFUS is weak, and that the one carefully conducted prospective case series ranks as poor for informing clinical decision making.
 
Two new publications from the MRgFUS study group were identified. One of the reports compared results from patients treated with the original (33% of fibroid volume with a maximum treatment time of 120 min, n = 96) and modified (50% treatment volume, 180 min maximum treatment time, and a second treatment if within a 14-day period, n = 64) protocols.  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%). Interpretation of these results is 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. The second publication reported 24-month follow-up from three Phase 3 trials and one post-marketing study (total of 416 patients).  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%. Less 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. In addition, the studies lack concurrent control groups; randomized controlled trials are needed to compare the efficacy and durability of MRgFUS with alternative treatments.
 
2010 Update
 
In 2009, Taran and colleagues reported outcomes for the hysterectomy group (Taran, 2009).  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; safety data were also reported. A significantly higher proportion of women in the hysterectomy group reported at least one adverse event compared to women in the MRgFUS group. 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 in the MRgFUS group and 8 of 83 in the hysterectomy group. At 6 months, there were significantly higher scores in the hysterectomy group on 2 out of 8 sub-scales on the SF-36; scores on the remaining subscales did not differ significantly between groups. The SF-36 scores are 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 is not clear why the original primary outcome, the SSS, was not reported.
 
There are several prospective case series reports from Japan on the efficacy and safety of MRgFUS for treating uterine fibroids. A series from Tokyo published in 2008 included 48 women, over 18 years of age, who were candidates for surgical intervention due to symptomatic fibroids (Morita, 2008).  During the 12-month follow-up period, 2 patients required surgical interventions, and 2 patients required additional drug treatment for fibroids. The average reduction in fibroid volume determined by MR imaging at 6 months after treatment was 33%. This volume reduction is correlated with the fibroid's treated volume (range: 35-115mm). No serious complications were recorded during the treatments or follow-up period. The patients were asked about subjective relief of symptoms and if they sought additional treatments. The authors concluded that MRgFUS can safely be used to noninvasively treat symptomatic uterine fibroids and avoid the need for surgical intervention in the short term.
 
A case series by Funaki and colleagues included 91 women (141 uterine fibroids) from a single center in Kobe, Japan; like the other Japanese case series, the study included women who were candidates for conventional surgery due to symptomatic fibroids (Funaki, 2009).  Outcomes were assessed at 6, 12 and 24 months after MRgFUS treatment. Fibroids were classified into 3 types based on the signal intensity of pre-treatment T2-weighted MRI images. Type 3 had the highest signal intensity (equal to or higher than that of the myometrium); the center no longer treats these types of fibroids with MRgFUS due to poor outcomes, and the 11 women with type 3 myomas were excluded from some analyses. The Symptom Severity Score of 72 patients with type 1 and 2 leiomyomas was a mean of 35.1 (standard deviation=21) before treatment and decreased significantly starting at 3 months follow-up; this decrease was maintained for up to 24 months. The mean volume change ratio for types 1 and 2 leiomyomas decreased a mean of 36.5% six months post-treatment and decreased a mean of 39.5% at 24 months. Type 3 fibroids did not show a reduction in size 6 months after treatment. Twelve of the 80 type 1 and 2 patients had additional interventions after a median of 34 months (range 6-64 months) due to unsuccessful outcomes. Five women had repeat MRgFUS treatments, 3 had a hysterectomy or myomectomy and 3 had transcervical resections.
 
A prospective registry of pregnancies after MRgFUS had been maintained by the manufacturer of the ExAblate device. A 2008 article reported that there were 54 known pregnancies a mean of 8 months after treatment (Rabinovici, 2008). 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 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.
 
Several ongoing randomized controlled trials were identified. Insightec is sponsoring a trial comparing MRgFUS to myomectomy, in women with uterine fibroids who desire pregnancy (NCT00730886). In addition, the Mayo clinic is sponsoring a trial comparing MRgFUS to uterine artery embolization; desire for pregnancy is not an inclusion or exclusion criteria but women who are pregnant or actively trying to become pregnant are ineligible (NCT00995878). As of April 2010, the Mayo clinic sponsored trial is actively recruiting participants.
 
A 2009 review article states that, in addition to the treatment of uterine fibroids, MRgFUS is being evaluated for several clinical conditions including the ablation of benign and malignant tumors, and palliative therapy of bone pain associated with metastases (Jolesz, 2009). The author, who has financial links to Insightec, concludes, “At an early stage of development, MRgFUS’s safety and efficacy to address specific diseases must be demonstrated through rigorous clinical trials that are scrutinized by regulatory agencies including the FDA.”
 
Breast Tumors
Limited data are available for the application of MRgFUS in the breast. Six reports of feasibility studies are available describing preliminary results of using MRgFUS in the breast, and the first case report using this technique for breast cancer was published in 2001. A total of 73 treated patients have published data; 9 were treated for benign tumors, 40 were treated for malignancy with subsequent resection for histopathologic analysis, and 24 non-surgical candidates/refused surgery patients were treated as adjuvant therapy to existing tamoxifen protocols. Fibroadenoma, ductal carcinomas, adenocarcinomas, and lobular carcinomas have been treated. The adverse effects profile includes a few second-degree skin burns, and protocols maintain a roughly 1-cm distance between the tumor margin and the skin or rib cage. Residual tumor in the treated area appears to be a problem, with authors recommending treatment of the entire tumor plus 1 cm of surrounding tissue, as is done in lumpectomy. No long-term outcome studies are available.
 
Brain Cancer
Investigators are working to overcome the major obstacle of MRgFUS treatment in brain cancer applications—the skull. The skull bone attenuates and distorts the ultrasound beam propagation such that FUS treatments published to date involve removal of the skull bone. Specialized equipment is under development, and study using phased array transducer ‘helmets’ that are adjusted to correct for ultrasound beam distortion. A phase I clinical trial is underway, but no data in humans are available (Jaaskelainen, 2003).  
 
Palliative Treatment of Bone Metastases
There are several prospective Insightec-sponsored studies evaluating MRgFUS for the treatment of bone metastases. Gianfelice and colleagues treated 11 patients at one institution in Canada with painful bone metastases who had failed other available treatment options (Gianfelice, 2008). The mean visual analog scale (VAS) pain score was 6.0 (out of 10) at baseline; this decreased to 1.3 at 1 month and 0.5 at 3 months. All patients reported a decrease in the intake of analgesics; 7 patients stopped using pain medication for their bone metastases. Liberman and colleagues conducted a multicenter study, with sites in Canada, Israel and Germany. 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 (Liberman, 2009).  The mean VAS score decreased from 5.9 before treatment to 1.8 three months after treatment. Thirteen out 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. Independent verification of treatment effects with larger groups of patients is needed.
 
Technology Assessments, 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 (AHRQ, 2007).
 
No guideline or position statement from the American College of Obstetrics and Gynecologists (ACOG) was identified on MRgFUS for treatment of uterine fibroids.
 
Summary
MRgFUS is only FDA-approved 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. Other than the lack of randomization, this study was limited in that data on the comparison group was not published until 5 years after data on the treatment group, the clinical significance of the primary outcome is unclear and there was only one-year follow-up. There is insufficient evidence on the long-term treatment effects, recurrence rates and impact on future fertility and pregnancy.
 
MRgFUS is being investigated for use in several applications that are not currently approved by the FDA. There are some preliminary reports of safety and efficacy in small number of patients. There is insufficient evidence on the impact on health outcomes for treatment of other benign and malignant tumors.
 
2012 Update
A literature review conducted through January 2012 did not identify any new information that would prompt a change in the coverage statement.
 
MRI-guided focused ultrasound is currently being studied in a clinical trial. The FIRSST: Comparing MRgFUS (MR guided Focused Ultrasound) versus UAE (Uterine Artery Embolization) (NCT00995878): 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. The expected date of final data collection is January 2012.
 
2013 Update
This policy is being updated with a literature search of the MEDLINE database. There was no new information identified that would prompt a change in the coverage statement. The following ongoing clinical trials were identified on the clinicaltrials.gov website:
 
The FIRSST: Comparing MRgFUS (MR guided Focused Ultrasound) versus UAE (Uterine Artery Embolization) (NCT00995878): 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. Estimated enrollment is 180 patients.
 
Study Comparing the Safety and Effectiveness of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) and External Beam Radiation (EBRT) for Treatment of Metastatic Bone Tumors and Multiple Myeloma (NCT01091883)): This RCT is comparing MRgFUS to EBRT in adult patients with painful bone metastasis (i.e., worse numeric rating scale [NRS] pain score at least 4 out of 10). The study is sponsored by Insightec. Expected enrollment is 60 patients.
 
2014 Update
 
A literature search was conducted using the MEDLINE database through February 2014. There was no new information identified that would prompt a change in the coverage statement. The following is a summary of the key identified literature.
 
To date, no randomized controlled trials (RCTs) have been published using MRgFUS. A systematic review, published by Gizzo et al in 2013, identified 38 uncontrolled studies with a total of 2500 patients who underwent MRgFUS for treatment of uterine fibroids (Gizzo, 2013). All of the published studies included women older than age 18 years with symptomatic uterine fibroids, and most excluded patients who desired future pregnancies. The authors of the systematic review did not pool study findings. The review confirms the continued absence of published controlled studies on MRgFUS for uterine fibroids.
 
Several other nonrandomized comparative studies have been published. In 2013, Froeling et al reported on 121 women with symptomatic uterine fibroids who were equally eligible for treatment with MRgFUS and uterine artery embolization (UAE) (Froeling, 2013). Forty-four (36%) women were lost to follow-up. Follow-up data at approximately 60 months were available on 77 women, 41 in the UAE group and 36 in the MRgFUS group. The primary study outcome was the rate of reintervention (eg, repeat MRgFUS, myomectomy, hysterectomy, endometrial ablation). During follow-up, 5 (12%) women in the UAE group and 24 (67%) women in the MRgFUS group experienced a reintervention (statistical comparison not reported).Healthcare QOL scores, secondary outcomes, were significantly better in the UAE group compared with the MRgFUS group at follow-up. Fennessy et al compared 2 variations on the MRgFUS procedure.(7) 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.
 
Several manufacturer-sponsored case series on MRgFUS for pain palliation in bone metastases have been published (Liberman, 2009; Napoli, 2013). For example, in 2009, Liberman et al published findings of a multicenter prospective study conducted in Canada, Israel, and Germany (Liberman, 2009). The study included 31 patients with painful bone metastases who had failed or refused other treatment options; 25 patients (81%) were available for 3-month follow-up. The mean visual analog scale score decreased from 5.9 before treatment to 1.8 three months after treatment. Thirteen of 25 patients who used nonopioid analgesics and 6 of 10 who used opioids decreased medication use after treatment. Neither group reported any treatment-related adverse effects.
    
2015 Update
 
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Palliative Treatment of Bone Metastases
An RCT evaluating the ExAblate MRgFUS system was published by Hurwitz and colleagues (Hurwitz, 2014).  Previously, findings of this study, the pivotal trial leading to FDA approval of the device for treatment of painful bone metastases, were available on the FDA website. Data from the published version of the study are described here. The study included patients with at least 3 months of life expectancy who had bone metastases that were painful despite radiotherapy treatment or who were unsuitable for or declined radiotherapy. Patients needed to rate tumor pain on a numeric rating scale (NRS) at least 4 out of a maximum score of 10. They could have up to 5 painful lesions; however, only 1 lesion was treated and it had to cause at least 2 points greater pain on the NRS than any other lesion. In addition, targeted tumors needed to be device accessible.
 
Study participants were randomized in a 3:1 ratio to active (n=122) or sham (n=39) MRgFUS treatment. Ten patients in the treatment group and 4 in the sham group did not receive the allocated treatment. An additional 26 patients in the treatment group and 23 in the sham group did not complete the 3-month follow-up. A much larger proportion of the placebo group dropped out; 17 of 35 who were treated (49%) decided to have rescue MRgFUS treatment after lack of response to placebo. A modified intention to treat analysis was used that included patients who had at least 1 MRgFUS or placebo sonication. Missing values were imputed using the last observation carried forward method.
 
The primary efficacy outpoint, assessed at 3 months, was a composite outcome comprised of change in baseline in worst NRS score and morphine equivalent daily dose (MEDD) intake. Patients were considered responders if their worst NRS score decreased by at least 2 points and if their MEDD intake did not increase more than 25% from baseline to 3 months. NRS score and MEDD intake separately were reported as secondary outcomes.
 
Seventy-two of 112 (64.3%) patients in the MRgFUS group and 7 of 35 patients (20%) in the control group were considered responders, as defined above. The difference between groups was statistically significant (p=0.01), favoring active treatment. When the two measures that made up the primary endpoint were analyzed separately, there was a statistically significant difference between groups in change in worst NRS score and a nonsignificant difference in change from baseline in pain medication. The NRS score decreased by a mean of 3.6 points (SD=3.1) in the MRgFUS group and a mean of 0.7 (SD=2.4) in the placebo group (p<0.01). Change in MEDD was only reported in a figure. Fifty-one patients (45.5%) in the MRgFUS group and 1 (2.9%) in the placebo group experienced at least 1 adverse event. The majority of adverse events were transient and the most common was sonication pain, experienced by 36 patients (32.1%) in the MRgFUS group. In 17 patients (15.2%), sonication pain was severe; 3 patients did not complete treatment due to pain. The most clinically significant adverse events that lasted more than a week were third-degree skin burns in 1 patient (associated with noncompliance with the treatment protocol) and fracture in 2 patients (one of which was outside the treatment location). Potential limitations of the trial include a nonconventional primary outcome measure and, the small initial size of the sham group. Moreover, a large number of sham patients (66%) did not complete the 3-month follow-up; however, the authors stated that this low completion rate was due to lack of response to placebo treatment.
 
 
Ongoing and Unpublished Clinical Trials
A search of the ClinicalTrials.gov database on December 10, 2014, identified the following ongoing RCTs evaluating the FDA-approved MRgFUS device.
 
  • The FIRSST: Comparing MRgFUS (MR guided Focused Ultrasound) versus UAE (Uterine Artery Embolization) (NCT00995878): This is an RCT comparing MRgFUS with UAE in premenopausal women at least 25 years of age who have symptomatic uterine fibroids. The study is sponsored by the Mayo Clinic. Estimated enrollment is 180 patients with an estimated completion date of December 2015.
  • ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors (NCT01827904): This is a double-blind, sham-controlled RCT evaluating transcranial MRgFUS treatment in patients with a diagnosis of essential tremor who experience significant disability from the condition despite medical treatment. The study is sponsored by InSightec. Estimated enrollment is 72 patients and the expected date of study completion is September 2015.
  • ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Parkinson’s Disease (NCT01772693): This is a feasibility trial comparing MRgFUS to sham treatment in patients with idiopathic Parkinson disease who experience significant disability from tremor associated with the condition. The study is sponsored by InSightec. Estimated enrollment is 30 patients. The stated expected date of study completion is September 2014; however, as of December 2014, patients continue to be recruited.
 
2018 Update
 
A literature search conducted through January 2018 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
UTERINE FIBROIDS
Evidence for the use of MRgFUS for the treatment of uterine fibroids consists of 2 small RCTs and many observational studies.
 
In 2017, Barnard et al published preliminary results from Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT) study, a parallel RCT and cohort study comparing MRgFUS with fibroid embolization for the treatment of uterine fibroids (Barnard, 2017). For the RCT, patients were randomized to uterine artery embolization (UAE; n=22) or to MRgFUS (n=27). Patients and investigators were not blinded. Women who did not want to be randomized were enrolled in the cohort study; 16 underwent UAE and 16 underwent MRgFUS. Patients were instructed to keep diaries with the following information: medication use, return to normal activities, and symptoms. After 6 weeks of follow-up for the RCT patients, there were no differences between groups in symptoms such as fatigue, hot flashes, discomfort urinating, vaginal discharge, or constipation. Recovery was significantly faster in the MRgFUS group, as measured by the first day back to work and first day back to normal. Medication use (ie, opioids, nonsteroidal anti-inflammatory drugs, acetaminophen or aspirin, nausea medication, bowel medication) was also significantly lower in the MRgFUS group. Analyses combining the RCT and cohort patients showed similar results. The MRgFUS procedure took significantly longer than the UAE procedure. A limitation of the trial was the inability to recruit more patients. Long-term follow-up results will be forthcoming. In 2016, a pilot sham-controlled randomized trial evaluating MRgFUS for the treatment of uterine fibroids was published by Jacoby et al (Jacoby, 2016). The trial included 20 premenopausal women with symptomatic uterine fibroids (women who were pregnant or had a desire for future children were excluded). Patients were randomized to MRgFUS with the ExAblate 2000 System (n=13) or to a sham treatment not using thermal energy (n=7). The investigators did not specify primary outcomes. The sample size was calculated to assess the feasibility of a larger trial, not to provide sufficient statistical power. All patients were assigned to the MRgFUS group and 6 of 7 in the placebo group received their allocated treatment; all patients who were treated completed 3 months of follow-up. Patients were unblinded at 3 months, and those in the sham group were given the option of active treatment. QOL outcomes included the Uterine Fibroid Symptom and Quality of Life Questionnaire, which has subscales including the symptom severity score (SSS) and health related quality of life score. The 36-Item Short-Form Health Survey (SF-36), which includes the Mental Component Summary and Physical Component Summary, was also used. At 4- and 12-week follow-ups, there were no statistically significant differences (at the p<0.05 level) between the MRgFUS and the sham groups in the SSS, the health related quality of life score, and SF-36 Physical Component Summary or Mental Component Summary scores. Change in uterine and fibroid volume, however, differed significantly between groups at 12 weeks. Uterine volume decreased by 17% in the MRgFUS group and by 3% in the sham group (p=0.04). Total fibroid volume decreased by 18% in the MRgFUS group and did not change in the sham group (p=0.03). The authors concluded that women would be willing to participate in a sham-controlled randomized trial of MRgFUS and that larger trials were feasible.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2018. The key identified literature is summarized below.
 
ESSENTIAL TREMORS
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Systematic Reviews
The technology assessment was published by Health Quality Ontario (HQO, 2018). The literature search, conducted through April 2017, identified 9 studies for inclusion: 4 single cohort studies, 2 retrospective chart reviews, 2 uncontrolled prospective studies, and an RCT. The RCT compared MRgFUS with sham treatment, the chart reviews compared MRgFUS with deep brain stimulation and radiofrequency thalamotomy. Study quality was evaluated using the GRADE system. The RCT was rated high-quality, the uncontrolled comparative studies were rated very low quality, and the remaining studies were rated low quality. All studies reported tremor severity as an outcome. Pooling of results was not conducted due to heterogeneity in study designs, analyses, and outcomes across the studies. Reviewers determined that, overall, MRgFUS decreased tremor severity and improved QOL. The high-quality RCT by Elias et al is discussed below (Elias, 2016).
 
Mohammed et al conducted a meta-analysis evaluating the use of MRgFUS to treat medicine-refractory essential tremors (Mohammed, 2018). The literature search, conducted through August 2017 identified 9 studies (total N=160 patients) for inclusion, 8 of which were also evaluated in the Ontario technology assessment. Pooled analyses found significant improvements in the mean percentage change in Clinical Rating Scale for Tremor scores (62.2%) and Quality of Life in Essential Tremor scores (46.5%). Complications included nausea, vomiting, and ataxia, which decreased during the 12-month follow-up.
 
Randomized Controlled Trials
In 2016, a single high-quality study, a double-blind, sham-controlled randomized trial by Elias et al, was identified by the 2 systematic reviews (Elias, 2016). Trial selection criteria included patients with moderate or severe postural or intention tremor of the hand (2 on the Clinical Rating Scale for Tremor) and refractory to at least two medical therapies. Patients were randomized to MRgFUS thalamotomy (n=56) or sham treatment (n=20). Outcomes were tremor severity, improvement, and QOL, measured at three months postprocedure. Patients in the treatment group were followed for an additional 12 months. Mean score for hand tremor improved significantly from baseline in the treatment group (47%) compared with the sham group (0.1%) at 3 months. Change in mean functional improvement score from baseline differed significantly in the MRgFUS group (62%) compared with the sham group (3%) at 3 months. Change in Quality of Life in Essential Tremor Questionnaire scores also differed significantly in the treatment group compared with the sham group, with the largest improvements experienced in the psychosocial domain. The improvements in hand tremor score, functional improvement, and QOL were maintained at 12 months in the MRgFUS group.
 
Chang et al published results from 67 patients who participated in the open-label extension of the RCT Chang, 2018). Because nine patients from the original trial received additional treatment during the two-year follow-up, they were excluded from the analysis. Improvements in tremor and disability scores were maintained at the 2-year follow-up (tremor, 19.8 ± 4.9 [baseline] to 8.8 ± 5.0 [at 2 years]; disability, 16.4 ± 4.5 [baseline] to 6.5 ± 5.0 [at 2 years]).
 
Section Summary: Essential Tremors
Evidence for the use of MRgFUS in the treatment of medicine-refractory essential tremors consists of a technology assessment that included a high-quality RCT; a meta-analysis; and a noncomparative study published after the technology assessment. The assessment did not pool results from the studies but concluded, overall, MRgFUS decreased tremor severity and improved QOL. The meta-analysis, which included nine studies total (eight were also in the technology assessment), found that MRgFUS significantly improved Clinical Rating Scale for Tremor scores as well as QOL measures. The sham-controlled randomized trial which was considered high-quality, found significant improvements in the treatment group in tremor severity, functional improvement, and QOL after three months of follow-up, and these results were maintained through two years of follow-up.
 
For individuals with medicine-refractory essential tremors who receive MRgFUS, the evidence includes two systematic reviews that identified an RCT and several observational studies. Relevant outcomes include symptoms, functional outcomes, quality of life, and treatment-related morbidity. The assessment did not pool study results but concluded that, overall, MRgFUS decreased tremor severity and improved quality of life. The sham-controlled randomized trial found significant improvements in the treatment group in tremor severity, functional improvement, and quality of life after three months of follow-up. The improvements in hand tremor score, function, and quality of life were maintained at the two-year follow-up. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
 
PRACTICE GUIDELINES AND POSITION STATEMENTS
 
Society of Obstetricians and Gynaecologists of Canada
The Society of Obstetricians and Gynaecologists of Canada published practice guidelines on the management of uterine fibroids in women with otherwise unexplained infertility (Carranza-Mamane, 2015). The guidelines found no studies comparing magnetic resonance‒guided focused ultrasound with myomectomy or in women with fibroids who had infertility as their primary complaint, and thus additional data would be needed before the treatment could be offered to this patient population.
 
American Society for Radiation Oncology
The American Society for Radiation Oncology published guidelines on palliative radiotherapy for bone metastases, which stated that external-beam radiotherapy continues to be the primary therapy for treating painful uncomplicated bone metastases (Lutz, 2017). The guidelines did not mention magnetic resonance-guided focused ultrasound If patients experience persistent or recurrent pain more than one month after initial treatment, the guidelines recommended retreatment with external-beam radiotherapy. As for advanced radiotherapy such as stereotactic body radiotherapy for retreatment of recurrent pain, these “may be feasible, effective, and safe, but the panel recommends that this approach should be limited to clinical trial participation or on a registry given limited data supporting routine use.”
 
National Comprehensive Cancer Network
Guidelines from the National Comprehensive Cancer Network on bone cancer (v. 2.2018), breast cancer (v. 1.2018), brain cancer (v. 1.2018), and prostate cancer (v. 2.2018) do not mention magnetic resonance-guided ultrasound as a treatment option (NCCN, 2018).  
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2019. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Mohammed et al conducted a meta-analysis evaluating the use of MRgFUS to treat medicine-refractory essential tremors (Mohammed, 2018). The literature search, conducted through August 2017 identified 9 studies (total N=160 patients) for inclusion, 8 of which were also evaluated in the Ontario technology assessment. Pooled analyses found significant improvements in the mean percentage change in Clinical Rating Scale for Tremor scores (62.2%) and Quality of Life in Essential Tremor scores (46.5%). Complications included nausea, vomiting, and ataxia, which decreased during the 12-month follow-up.
A single high-quality study, a double-blind, sham-controlled randomized trial by Elias et al, was identified by the 2 systematic reviews (Elias, 2016). Trial selection criteria included patients with moderate or severe postural or intention tremor of the hand (2 on the Clinical Rating Scale for Tremor) and refractory to at least 2 medical therapies. Patients were randomized to MRgFUS thalamotomy (n=56) or sham treatment (n=20). Outcomes were tremor severity, improvement, and QOL, measured at 3 months postprocedure. Patients in the treatment group were followed for an additional 12 months. Mean score for hand tremor improved significantly from baseline in the treatment group (47%) compared with the sham group (0.1%) at 3 months. Change in mean functional improvement score from baseline differed significantly in the MRgFUS group (62%) compared with the sham group (3%) at 3 months. Change in Quality of Life in Essential Tremor Questionnaire scores also differed significantly in the treatment group compared with the sham group, with the largest improvements experienced in the psychosocial domain. The improvements in hand tremor score, functional improvement, and QOL were maintained at 12 months in the MRgFUS group.
 
Chang et al published results from 67 patients who participated in the open-label extension of the RCT (Chang, 2018). Because 9 patients from the original trial received additional treatment during the 2-year follow-up, they were excluded from the analysis. Improvements in tremor and disability scores were maintained at the 2-year follow-up (tremor, 19.8±4.9 [baseline] to8.8±5.0 [at 2 years]; disability, 16.4±4.5 [baseline] to 6.5±5.0 [at 2 years]).
 
Practice Guidelines and Position Statements
 
Society of Obstetricians and Gynaecologists of Canada
The Society of Obstetricians and Gynaecologists of Canada published practice guidelines on the management of uterine fibroids in women with otherwise unexplained infertility (Carranza-Mamane, 2015). The guidelines found no studies comparing magnetic resonance-guided focused ultrasound with myomectomy or in women with fibroids who had infertility as their primary complaint, and thus additional data would be needed before the treatment could be offered to this patient population.
 
2020 Update
A literature search was conducted through June 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Baal et al conducted a systematic review of studies published between 2007 and 2019 evaluating MRgFUS treatment for painful bone metastases (Baal, 2021). A total of 33 studies were identified, comprised of 3 RCTs, 6 retrospective studies, and 24 prospective studies, representing 1,082 patients. Thirteen studies were available in abstract form only. The median study sample size was 21 patients (range 5 to 140) with a median follow-up period of 3 months (range, 1 to 12 months). Efficacy was assessed by treatment response (complete response or partial response [2-point improvement in pain score]) and the mean difference in pain scores (10- point VAS [visual analog scale] or NRS [numeric rating scale]) from baseline to month 1/month 3. The pooled proportion of patients with a treatment response to MRgFUS was 79% (95% confidence interval [CI], 73% to 83%; based on 20 studies [n=636]). The pooled 1-month and 3-month mean difference from baseline in pain score were -3.8 (95% CI, -4.3 to -3.3) and -4.4 (95% CI, -5.0 to - 3.7), respectively (based on 20 studies [n=543]). Across 26 studies (n=799), 7 high-grade adverse events were observed (1 deep vein thrombosis, 2 cases of grade 3 skin burn, and 4 fractures). Approximately 11.8% of patients experienced sonication-related pain during MRgFUS treatment. The analysis was limited by a lack of a pooled comparator. Additionally, there was substantial heterogeneity of the included studies due to variable study populations (eg, type of primary cancer), reported data, and treatment details. The majority of the included studies had follow-up periods that were limited to 3 months.
 
Ghai et al conducted a phase II trial to evaluate the safety and efficacy of transrectal MRgFUS treatment for intermediate-risk prostate cancer (Ghai, 2021). The primary efficacy endpoint was the presence of residual disease at the treatment site at 5 months after the procedure. Ninety-three percent of patients were free of clinically significant prostate cancer at the 5-month biopsy. No major treatment-related adverse events occurred. Study limitations include the short follow-up time to assess efficacy; however, a biopsy at a 24-month follow-up is planned, which will address persistence and recurrent prostate cancer.
 
Arrigoni et al conducted a propensity score-matched retrospective study to compare treatment with radiofrequency ablation and MRgFUS (Arrigoni, 2021). A total of 116 patients were treated (61 with radiofrequency ablation and 55 with MRgFUS). After propensity score matching, both radiofrequency ablation and MRgFUS treatment resulted in a significant reduction in pain from baseline as measured by VAS (8.9 to 0.02 and 8.8 to 0.54, respectively). There was no statistically significant difference between the mean values of both groups after the treatment. Four cases of relapse (1 with radiofrequency ablation and 3 with MRgFUS) were observed. Arrigoni et al prospectively enrolled children into a study to evaluate MRgFUS treatment for osteoid osteoma (Arrigoni, 2019). The primary clinical endpoint was defined as the absence of pain (evaluated on the Faces Pain Scale-Revised) at the first follow-up study 1 week after the procedure. A total of 33 children were included in the study and treated with MRgFUS. The mean pain score at baseline was 7.6; the score at week 1 after the procedure significantly improved in all children (mean score, 0.21). Complete absence of pain was reported in 32 of 33 (97%; 95% CI, 84 to 100) of patients at week 1. At the 24-month follow-up visit, imaging results confirmed the complete disappearance of bone edema around all lesions.
 
Miller et al published a meta-analysis that evaluated the efficacy of MRgFUS for treating medication-refractory ET with a focus on long-term trends and the durability of the response (Miller, 2021). Twenty-one studies (N=395) were included; 17 were prospective studies, 3 were retrospective, and only 1 was an RCT (Elias, 2016). Hand tremor scores decreased from a weighted mean pre-operative value of 19.2±5.0 to 7.4±5.0 after 3 months. Over time, the hand tremor score values gradually increased: 8.3±5.3 after 12 months and 9.1±5.4 after 36 months. The pooled standardized mean difference of hand tremor scores compared to pre-treatment values was 2.68 (95% CI, 1.94 to 3.41) at 3 months (5 studies), 2.44 (95% CI, 1.97 to 2.91) at the 12-month time point (7 studies), and 2.18 (95% CI, 1.50 to 2.86) at the 24-month time point (3 studies). Clinical Rating Scale for Tremor scores were only reported through 12 months. The pooled standardized mean difference in Clinical Rating Scale for Tremor scores compared to pre-treatment values was 1.86 (95% CI, 1.51 to 1.21) at the 3-month time point (8 studies) and 2.24 (95% CI, 1.55 to 2.94) at the 12-month time point (6 studies). Six studies reported Quality of Life in Essential Tremor Questionnaire (QUEST) scores as a quality of life measure. The pooled pre-treatment QUEST score was 48.2±22.4, which improved to 24.9±18.2 at 3 months. Additionally, a single study detailed a mean 23.8±19.6 QUEST score at 36 months follow-up, an increase of 2.2 over 30 months.
 
Giordano et al conducted a meta-analysis to compare unilateral MRgFUS to unilateral and bilateral DBS for medication-refractory ET (Giordano, 2020). Forty-five studies published between 1996 and 2019 were identified. Thirty-seven studies (n=1,202) evaluated DBS and 8 studies (n=477) evaluated MRgFUS. Fifteen studies had a retrospective study design, while 30 were prospectively designed. Means and standard deviations were calculated for each intervention and differences between groups were compared where appropriate. The average percentage improvement in tremor severity was significantly improved in the pooled DBS group (60.1% ±9.7%) as compared to the MRgFUS group (55.6%±8.2%, p<.001). Subgroup analyses demonstrated that the improvement in tremor severity was significantly greater with the bilateral DBS (61.2%±5.2%) as compared to both unilateral DBS (56.4%±9.7%) and MRgFUS; there was no significant difference between unilateral DBS and MRgFUS. For average percentage improvement in quality of life, MRgFUS was associated with significantly improved measures as compared to DBS (61.9%±7.9% vs 52.5%±16.2%, p<.001). There were 517 complications reported in the DBS group and 484 complications reported in the MRgFUS group. The most common adverse events reported with DBS were lead-related complications (11.4%) and speech disturbances (11.1%). For MRgFUS, adverse events of sensory nature (36.7%) and gait disturbances/muscle problems (34.4%) were most common. Limitations of the review included the different scales used in studies to measure tremor severity and quality of life. There was only 1 retrospective study that directly compared DBS and MRgFUS.
 
A double-blind, sham-controlled, pilot randomized trial by Bond et al assessed the safety and efficacy of unilateral MRgFUS thalamotomy in patients with tremor-dominant PD (Bond, 2017). The primary efficacy outcome evaluated was the change from baseline (on-medication state) to 3 months after the procedure in the hand tremor subscore in the Clinical Rating Scale for Tremor. After unblinding at 3 months, 6 of the 7 patients who received sham procedures crossed over to undergo open-label treatment with MRgFUS. The most common thalamotomy-related adverse events reported for all 26 patients treated were finger paresthesia (39%), ataxia (35%), and orofacial paresthesia (27%). Paresthesia and ataxia persisted to 1 year in 19% and 4% of patients, respectively. Eight severe adverse events were reported in 4 patients, and 3 were thalamotomy-related (2 patients with persistent mild hemiparesis and 1 patient had an associated persistent mild ataxia).
 
The American College of Radiology Appropriateness Criteria for the radiological management of uterine leiomyomas (fibroids) (Knuttinen, 2018). The clinical guidance states that "MR-guided high-intensity focused US (MRgFUS) is another uterine-sparing option to treat focal leiomyomas. It is noninvasive, though each treatment may take several hours to complete. Its use currently is restricted to patients with fewer than six leiomyomas or leiomyoma volume < 900 cm3," and "although a reasonable alternative for patients unable or unwilling to tolerate sedation or anesthesia, long-term data and viability results are still lacking."
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Long-term follow-up results were reported by Laughlin-Tommaso et al (Laughlin-Tommaso, 2019). Patients in both the RCT and cohort studies had follow-up for up to 3 years. The primary outcome assessed was reintervention for uterine fibroids within 3 years; secondary outcomes included change in anti-Mullerian hormone levels and standardized measures of quality of life, pain, sexual function, and fibroid symptoms. Among the women in the MRgFUS arm (n=43), 13 (30%) had a second fibroid procedure compared to 5 (13%) women in the UAE arm (hazard ratio [HR], 2.81; 95% confidence interval [CI], 1.01 to 7.79). Both quality of life and pain scores improved in both arms, however there was a larger improvement in the UAE arm. There was a significantly greater absolute decrease in anti-Mullerian hormone levels at 24 months in the UAE arm compared to the MRgFUS arm.
 
A meta-analysis by Xu et al compared the reintervention rates of UAE, myomectomy, and MRgFUS in patients with uterine fibroids (Xu, 2021). There were 31 studies (N=42103) that were included in the analysis, with 6 being RCTs and the other 25 being cohort studies. The 12-month, 24-month, 36-month and 60-month re-intervention rates were assessed as the primary outcome. Myomectomy has the lowest re-intervention rate of the 3 regimens in all time points assessed while the MRgFUS had the highest re-intervention rate. The estimations of the pooled rates of reintervention of MRgFUS also increased rapidly in the sixtieth month after treatment compared to myomectomy and UAE.

CPT/HCPCS:
0071TFocused ultrasound ablation of uterine leiomyomata, including MR guidance; total leiomyomata volume less than 200 cc of tissue
0072TFocused ultrasound ablation of uterine leiomyomata, including MR guidance; total leiomyomata volume greater or equal to 200 cc of tissue
0398TMagnetic resonance image guided high intensity focused ultrasound (MRgFUS), stereotactic ablation lesion, intracranial for movement disorder including stereotactic navigation and frame placement when performed

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