Medical Policy: 04.01.09
Original Effective Date: August 2007
Reviewed: January 2017
Revised: January 2016
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
An integrated system providing magnetic resonance imaging (MRI)-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, essential tremor and chronic neuropathic pain.
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.
To date, the primary clinical application of MRgFUS has been for treatment of uterine fibroids (leiomyomata) which is one of the most common conditions affecting geno typical 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. Further studies are needed to evaluate the efficacy and safety of MRgFUS relative to other treatments for uterine fibroids.
Essential tremor (ET) is one of the most common movement disorders. The cause of the disease and it pathomechanism are still unknown. The main symptoms include tremor of the hands, arms and head. The clinical course is frequently benign, however disability due to ET is common. Pharmacotherapy is usually the first line treatment and patients who do not respond to medications may be considered for surgical treatment (radiofrequency identification (RFID), stereotactic radiosurgery, gamma knife thalamotomy or deep brain stimulation). An alternative treatment being investigated for the treatment of essential tremor is the use of magnetic resonance guided focused ultrasound (MRgFUS) to produce thermal ablation of the thalamic ventral intermediate nucleus (i.e. MRI-guided focused ultrasound thalamotomy). Preliminary uncontrolled studies have shown improvement compared with baseline scores for contralateral hand tremor, disability and quality of life. Adverse effects included transient sensory and cerebellar symptoms; and persistent paresthesia. However, large, randomized, controlled trials are needed to determine the proper patient populations that may benefit from this therapy and assess the long term efficacy and safety of MRgFUS for this indication.
Chronic neuropathic pain is frequently the result of damage to or dysfunction of the nerve fibers which send incorrect signals to pain centers. Pain significantly lowers patients’ quality of life and complicates normal functioning. An alternative treatment being investigated for the treatment of chronic neuropathic pain is the use of magnetic resonance guided focused ultrasound (MRgFUS) to produce thermal ablation of areas within the thalamus. Uncontrolled studies with small patient populations have been completed treating patients with chronic neuropathic pain caused by a range of conditions including post herpatic neuralgia, avulsion of brachial plexus and lumbar nerve root compression. These preliminary uncontrolled studies have shown improvement in mean reduction in pain scores with minimal adverse events. However, large, randomized controlled trials are needed to assess the long term efficacy and safety of MRgFUS relative to other treatments for this indication.
MRI-guided high-intensity focused ultrasound (MRgFUS) ablation is also being studied as a treatment of other tumors including breast, prostate, liver, pancreas and brain, as well as palliative treatment of painful bone metastases.
Only small case series have been published investigating the safety and/or efficacy of MRgFUS for treating other tumors including breast cancer, brain cancer, prostate cancer, and nonspinal osteoid osteoma. Randomized controlled trials are needed to assess the long term efficacy and safety of MRgFUS for these indications.
Interest in minimally invasive local treatment options that target pain from bone metastases has increased because patient longevity and advances in cancer management have led to more people living with bone metastases. Magnetic resonance guided focused ultrasound (MRgFUS) is being used for palliating pain from bone metastases.
Bones are a common place for metastatic cancer cells to colonize and establish secondary tumor sites. Higher grade tumors and late diagnosis are also associated with the presence of bone metastasis. Metastases can develop in any bone, but certain cancers such as solid tumors (breast, prostate, lung, thyroid, and kidney cancers) are more likely than others to spread to bone, and bone metastases occur in late stages of most solid tumor cancers.
Bone metastases are common cause of significant morbidity or mortality, metastatic lesions can predispose the bone to fractures. When metastases form in bone, the cancer cells release substances that can activate nearby bone cells, called osteoclasts and osteoblasts. Osteoclasts dissolve and weaken surrounding bone, which can lead to formation of osteolytic lesions. Osteoblasts stimulate bone formation, causing sclerotic, osteoblastic lesions. Both types of bone metastases can cause pain, but osteolytic lesions usually lead to fracture more often than osteoblastic lesions.
Clinical condition, life expectancy, and impact on quality of life (QOL) guide pain palliation treatment decisions. First line treatment is pain medication with nonsteroidal anti-inflammatory drugs progressing to opioids. Increasing opioid doses can result in nausea, sedation, constipation, somnolence, and dependence, which negatively affects a patient’s QOL. External beam radiation therapy (EBRT) is the standard second line treatment for pain from bone metastases; however, radiation is effective in only 60% to 65% of patients, and pain relief may not occur in those patients for two to four weeks after treatment. EBRT is also limited by is cumulative radiation effects to healthy organs, bone and surrounding tissue. Patients who have previously had EBRT may be unable to tolerate additional EBRT. Furthermore, for patients who experience some relief from EBRT, the relief is only temporary for about 30% because of disease progression. Retreatment of patients who can be re-irradiated is effective only one about 30% of patients. Its effectiveness may be diminished by having to deliver a smaller dose because of concerns about cumulative radiation dose to normal tissues. Other systemic palliative therapies (e.g., chemotherapy, hormonal therapy, radioisotopes, bisphosphonates) are available; however, many patients experience inadequate pain control or unwanted side effects with these options. Thus, new options are needed, particularly for patients who are ineligible for EBRT.
More recent options involve methods to ablate the pain-transmitting cells at the boundary of bone tumors, which is believed to inhibit the patient’s ability to feel pain. One such option is magnetic resonance imaging (MRI) – guided focused ultrasound (MRgFUS). Unlike diagnostic ultrasound, which exposes tissue to biologically insignificant acoustic energy levels, MRgFUS energy acts on bone primarily through thermal effects. MRgFUS energy can rapidly heat tissue to the point at which irreversible thermal ablation and coagulative necrosis occurs. The outer covering of the bone is the target for MRgFUS energy as the bone tumor itself may be more or less absorptive depending on whether it is osterolytic or osteoblastic (or mixed). Bone is particularly conducive to MRgFUS ablation because of its higher ultrasound energy absorption, lower thermal conductance, and less susceptibility to penetration of ultrasound waves than soft tissue. As a result, the absorption pattern by bones allows wider surface areas of the bone to be treated with each energy pulse.
MRgFUS to palliate bone metastases typically requires locoregional anesethesia or a combination of local anesthesia and deep sedation. Clinicians typically perform MRgFUS in the outpatient setting. Treatment typically requires about 1.5 hours per lesion but may vary depending on tumor size and location. Immediately after the procedure, a technologist performs contract enhanced MRI scan to verify ablation and assess potential damage to tissues adjacent to the target bone sites.
The reported benefits of MRgFUS for palliation of bone metastases are as follows:
The Hurwitz et al. 2014 RTC provided comparative data on pain severity, analgesic use, QOL (quality of life), and pain response at various time points up to three month follow up. This multi-center phase III trial demonstrated that MRgFUS is a safe and effective, non-invasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.
The evidence for magnetic resonance-guided focused ultrasound (MRgFUS) in individuals who have uterine fibroids includes a pilot randomized controlled trial (RCT), nonrandomized comparative studies, and case series. The pilot randomized controlled trial reported some health outcomes, but its primary purpose was to determine the feasibility of a larger trial. It did not find statistically significant differences in quality of life outcomes between active and sham treatment groups, but it did find lower fibroid volumes after active treatment. The Food and Drug Administration trial was not randomized, the clinical significance of the primary outcomes was unclear, and there were no follow up data beyond 1 year. In the 2013 comparative study, outcomes appeared to be better with uterine artery embolization than with MRgFUS. There are insufficient data on the longer term effects, recurrent rates, and impact on future fertility and pregnancy. The evidence is insufficient to determine the effects of the technology on health outcomes.
The evidence for MRgFUS in individuals who have metastatic bone cancer who failed or are not candidates for radiotherapy includes a sham-controlled randomized trial. The RCT found statistically significant improvement after MRgFUS in a composite outcome comprised of reduction in pain and morphine use, and in pain reduction as a stand-alone outcome. A substantial proportion of patients in the treatment group experienced adverse events, but most of these were not severe and were transient. The evidence is sufficient to determine that the technology results in a meaningful improvement in net health outcomes.
The evidence for MRgFUS in individuals who have miscellaneous tumors (e.g. brain cancer, prostate cancer, breast cancer, liver cancer, pancreas cancer, osteoid sarcoma) includes case series. The evidence is insufficient to determine the effects of the technology on health outcomes. Further studies are needed to determine the long-term efficacy and safety of MRgFUS relative to other treatments for these indications.
The evidence for MRgFUS in individuals with essential tremor and chronic neuropathic pain is insufficient to determine the effects of the technology on health outcomes. Large randomized controlled trials are needed to determine the proper patient populations that may benefit from this therapy and assess long term efficacy and safety of MRgFUS for these indications.
Ablative strategies such as radiofrequency (RF) ablation and US ablation may also be performed to reduce pain and prevent skeletal related events (SREs).
MR-guided high intensity ultrasound is another uterine sparing option to treat focal leiomyomas. It is noninvasive, though each treatment may take several hours to be completed. Its use currently is restricted to patients with fewer than six leiomyomas or leimyoma volume less than 900 cm3. To date, there is little long term information on the efficacy of this technology.
Surgical Alternatives to Hysterectomy
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 U.S. Food and Drug Administration (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 U.S. Food and Drug Administration (FDA) approved the ExAblate Neuro system to treat essential tremor in patients who have not responded to medication. ExAblate Neuro uses magnetic resonance images taken during the procedure to deliver focused ultrasound to destroy brain tissue in a tiny area thought to be responsible for causing tremors.
See also medical policy 02.01.53 High Intensity Focused Ultrasound (HIFU)
MRI-guided high intensity ultrasound (MRgFUS) ablation may be considered medically necessary for pain palliation in adult patients with metastatic bone cancer who failed or are not candidates for radiotherapy.
MRI-guided high-intensity focused ultrasound (MRgFUS) ablation is considered investigational for all other indications including but is not limited to the following:
There is evidence from a sham-controlled, randomized trial that magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) improves the net health outcome for adults with painful bone metastases who failed or are unsuitable for radiotherapy treatment. There is insufficient evidence from randomized controlled trials, uncontrolled studies, and case series regarding the safety and efficacy of MRgFUS for patients with other clinical conditions. Therefore, MRgFUS may be considered medically necessary for pain palliation in adult patients with metastatic bone cancer who failed or are not candidates for radiotherapy and investigational for all other indications.
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