Focused Ultrasound Treatment of Painful Bone Metastases

Background

Bone is the third most common tissue affected by metastatic disease. Breast, lung, and prostate cancer metastasize to bone most frequently. Common symptoms of bone metastases include pain, fractures, spinal cord compression, and high blood calcium levels. One explanation regarding the source of the pain from bone metastases is the layer covering the outer surface of the bone called periosteum. The periosteum is rich with nerve fibers that produce pain when the membrane is irritated or damaged. Bone metastases can cause pain by direct or indirect sensitization of the periosteum.

Treatment

Current treatments for patients with bone metastases are primarily palliative and include localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormone therapy, radiopharmaceutical therapy, and bisphosphonate administration--although the primary goal of these systemic therapies is often to address the disease itself), and analgesic therapies (opioids and nonsteroidal anti-inflammatory medications). Researchers have also tested radiofrequency and cryoablation as treatment options for bone metastases. Each of these treatments attempts to improve quality of life and the patient’s functional level. Treatment with external beam radiation therapy (EBRT) is the standard of care for patients with localized bone pain, and it has a success rate (i.e., pain relief) of 70% to 80%.

Focused Ultrasound Treatment

Focused ultrasound, a completely noninvasive, radiation-free method to treat bone metastases, is already approved in Europe and other regions. Using this treatment modality in conjunction with image guidance, the physician administers appropriate pain mitigation and then directs a focused beam of acoustic energy through the patient’s skin, superficial fat layer, muscles, and other organs to heat the targeted bone and bone-tissue interface. This significant rise in temperature thermally coagulates the periosteal membrane surrounding the targeted bone and may even directly damage tumoral tissue in the targeted area. The destruction of the periosteum, which contains the pain-reporting nerve fibers, provides rapid pain palliation (similar to a dental root canal treatment). Although it is not suitable for all patients, focused ultrasound treatment for painful bone metastases has the benefit of not using ionizing radiation while still providing fast pain relief within a single session (sometimes faster than traditional radiation therapy).

Benefits of Focused Ultrasound

The potential benefits of focused ultrasound for the treatment of painful bone metastases are:

• It is a noninvasive, low morbidity treatment that allows for a quick return to normal life (usually the next day).
• It offers rapid and durable resolution of bone metastasis pain.
• A single therapy session is usually enough for significant symptomatic improvement.
• It has a reported low rate of complications.
• Treatment does not use ionizing radiation, which means:
  • It is possible to repeat focused ultrasound treatments to bone.
  • It is possible to treat patients who have reached their maximum dose of radiation for the targeted bone metastasis.
  • it is possible to combine radiotherapy for the primary tumor with focused ultrasound to the bone metastasis without creating local overdose.
• It has a theoretical advantage of reducing structural damage to bone and allowing faster bone healing after treatment.

Focused Ultrasound Patient Selection Criteria

• The patient suffers from pain originating from a localized bone metastasis.
• The patient should be able to receive conscious sedation.
• The patient should be able to communicate sensations to the physician during the procedure and be able to activate a “Stop Sonication” button.
• The targeted bone metastasis should be technically accessible to focused ultrasound devices and be located more than 1 cm away from skin, bowels, or major nerves.
  • Pelvis, scapula (a shoulder bones), ribs, and extremities are treatable.
  • Vertebral bodies, skull bones, and fingers are not treatable (in most cases).
• Care should be taken when performing focused ultrasound treatment on patients where the path of the ultrasound beam is through scar tissue or skin folds.
• Focused ultrasound treatment is contraindicated when the path of the ultrasound beam must travel through hollow viscera, surgical clips, or any hard implant that cannot be removed.
• Focused ultrasound treatment using MRI guidance is contraindicated in patients with MRI--related issues (e.g., the presence of metallic implants that are incompatible with MRI, sensitivity to MRI contrast agents, or the inability to fit into the MRI bore).

Clinical Trials

Physicians have used focused ultrasound to treat about 500 patients worldwide for painful bone metastases (mostly in research settings). Clinical studies* conducted at such world-renowned medical centers as Brigham and Women's Hospital‚ Mount Sinai at Toronto, Sunnybrook Health Sciences Centre (Toronto), Stanford University Medical Center, Moffitt Cancer Center (Tampa, FL), and Weill Cornell Medical College include:

• Magnetic Resonance-Guided High Intensity Focused Ultrasound for Palliation of Painful Skeletal Metastases
• ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Metastatic Bone Tumors for the Palliation of Pain
• 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
• Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System

*Studies listed at www.clinicaltrials.gov

Regulatory Approval

The following geographical regions have one or more focused ultrasound devices approved to perform focused ultrasound treatment of painful bone metastases: Europe (CE Mark), Korea (KFDA), India, and Russia.

Reimbursement

Because focused ultrasound treatment for painful bone metastasis has not yet been approved by the United States Food and Drug Administration, no United States payers have a public coverage policy.

Treatments are reimbursed in Italy and Germany.

In other countries, coverage may be available on a case-by-case or site basis.

Patient Advocacy

To increase patient awareness and access to focused ultrasound treatment for painful bone metastases outside the United States, InSightec, a company that manufactures focused ultrasound equipment, has sponsored a website for patients at: http://www.bone-pain-palliation.co.uk/

For general information about bone metastasis: http://www.cancer.org/Cancer/BoneMetastasis/DetailedGuide/index.htm

Sites Offering Focused Ultrasound Treatment

Equipment Manufacturers

ExAblate for bone metastasis by InSightec LTD

http://www.insightec.com/BoneMetastases.html

Note: see caution statement on this website stating the investigational status of the use of this device for the treatment of bone metastases in the United States.

Sonalleve MR-HIFU by Philips

http://www.healthcare.philips.com/main/products/mri/systems/sonalleve/index.wpd

Note: if an “Advisory Message” appears on the screen, click “Confirm and Continue to non-USA Page.” An American version of this page will not be available until the United States Food and Drug Administration grants approval for the use of focused ultrasound in treating bone metastases.

Model JC by Chongqing Haifu Technology Ltd

http://www.haifu.com.cn/en_main_3.asp

Notable Papers

1. Liberman B, Gianfelice D, Inbar Y, Beck A, Rabin T, Shabshin N, Chander G, Hengst S, Pfeffer R, Chechick A, Hananel A, Dogadkin O, Catane R. Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study. Ann Surg Oncol 2009 Jan;(1) 140-6. Epub 2008 Nov 11.
2. Gianfelice D, Gupta C, Kucharczyk W, Bret P, Havill D, Clemons M. Palliative treatment of painful bone metastases with MR imaging–guided focused ultrasound. Radiology 2008 Oct;249(1):355-63. Epub 2008 Aug 11.
3. Turkevich VG, Savelyeva VV, Kanaev SV, Dunaevsky IV, Krzhivitsky PI. Treatment of painful bone metastases with magnetic resonance guided focused ultrasound. Eur J Cancer 2011 Sep;47(Supl1):227-8.
4. Konski A. High-intensity focused ultrasound in the treatment of bone tumors: another treatment option for palliation and primary treatment? Cancer 2010 Aug 15;116(16):3754-5. [Comment on Cancer 2010 Aug 15;116(16):3934-42.]
5. Li CX, Zhang WD, Fan WJ, Huang JH, Zhang FJ, Wu PH. Noninvasive treatment of malignant bone tumors using high-intensity focused ultrasound. Cancer 2010 Aug 15;116(16):3934-42.