Bone Metastases

Background

Clinical KeyBone 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 the 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. 

Current 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); and analgesic therapies (opioids and non-steroidal anti-inflammatory medications). Researchers have also tested radiofrequency and cryoablation as treatment options, aimed at improving 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 non-invasive, radiation-free method to treat bone metastases, is approved in the United States, Europe, and other regions of the world. 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. However, it should be noted that focused ultrasound is not suitable for every patient.

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

  • It is a non-invasive, 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.

Regulatory Approval and Reimbursement

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

Treatments are reimbursed in Italy and Germany. Most major health insurers in the US also cover focused ultrasound for bone metastases. In other countries, coverage may be available on a case-by-case or site basis.

Treatment Sites

Please see here for a list of treatment sites in the US and the rest of the world

Clinical Trials

For a full list of known bone metastases clinical trials, please see here.

Notable Papers

 

Piper RJ, Hughes MA, Moran CM, Kandasamy J. Focused ultrasound as a non-invasive intervention for neurological disease: a review. Br J Neurosurg. 2016 Jun;30(3):286-93. doi: 10.3109/02688697.2016.1173189. Epub 2016 Apr 22.

Ringe KI, Panzica M, von Falck C. Thermoablation of Bone Tumors. vRofo. 2016 Mar 16.

Ten Eikelder HM, Bošnački D, Elevelt A, Donato K, Di Tullio A, Breuer BJ, van Wijk JH, van Dijk EV, Modena D, Yeo SY, Grüll H. Modelling the temperature evolution of bone under high intensity focused ultrasound. Phys Med Biol. 2016 Feb 21;61(4):1810-28. doi: 10.1088/0031-9155/61/4/1810. Epub 2016 Feb 8.

Rodrigues DB, Stauffer PR, Vrba D, Hurwitz MD. Focused ultrasound for treatment of bone tumours. Int J Hyperthermia. 2015;31(3):260–71.

Gu J, Wang H, Tang N, Hua Y, Yang H, Qiu Y, Ge R, Zhou Y, Wang W, Zhang G. Magnetic resonance guided focused ultrasound surgery for pain palliation of bone metastases: early experience of clinical application in China. Zhonghua Yi Xue Za Zhi. 2015 Nov 3;95(41):3328-32.

Brown MR, Farquhar-Smith P, Williams JE, ter Haar G, deSouza NM. The use of high-intensity focused ultrasound as a novel treatment for painful conditions-a description and narrative review of the literature. Br J Anaesth. 2015 Oct;115(4):520-30. doi: 10.1093/bja/aev302.

Yeo SY, Elevelt A, Donato K, van Rietbergen B, Ter Hoeve ND, van Diest PJ, Grüll H. Bone metastasis treatment using magnetic resonance-guided high intensity focused ultrasound. Bone. 2015 Dec;81:513-23. doi: 10.1016/j.bone.2015.08.025. Epub 2015 Aug 29.

Kobus T, McDannold N. Update on Clinical Magnetic Resonance-Guided Focused Ultrasound Applications. Magn Reson Imaging Clin N Am. 2015 Nov;23(4):657-67. doi: 10.1016/j.mric.2015.05.013. Epub 2015 Jul 7. Review.

deSouza N, Ward N. Magnetic resonance-guided high-intensity-focused ultrasound for the treatment of cancer-related pain. Pain Manag. 2015;5(4):221-4. doi: 10.2217/pmt.15.25. Epub 2015 Jun 19.

Sin Yuin Yeo, Andrés J. Arias Moreno, Bert van Rietbergen, Natalie D. ter Hoeve, Paul J. van Diest, and Holger Grüll. Effects of magnetic resonance-guided high-intensity focused ultrasound ablation on bone mechanical properties and modeling. Journal of Therapeutic Ultrasound 2015, 3:13  doi:10.1186/s40349-015-0033-8

Hurwitz M, Ghanouni P, Kanaev S, Iozeffi D, Gianfelice D, Fennessy F M, Kuten A, Meyer J E, LeBlang S D, Roberts A, Choi J, Larner J M, Napoli A, Turkevich V, Inbar Y, Tempany C M, Pfeffer. Magnetic Resonance-Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results. JNCI N Natl Cancer Inst 2014 Apr; 10.1093. 

Click here for additional references from PubMed.

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