High-Intensity Focused Ultrasound Treatment for Bone Metastases

  • Ronit Machtinger
  • Fiona M. Fennessy
  • Mark D. Hurwitz
Reference work entry


Bone metastases are a frequent complication of cancer which are often associated with severe morbidity, due to pain, pathologic fractures, and spinal cord compression. Current treatment options for bone metastases include external beam radiation, radionuclide therapy, analgesia, surgery, bisphosphonates, and ablation techniques. However, the treatments themselves might be associated with morbidity and side effects, and patients may experience persistent or recurrent pain. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a relatively new technique which has been shown to have potential as a noninvasive treatment option for a variety of benign and malignant tumors. Recent clinical trials have shown its benefit in palliative treatment of bone metastasis. This chapter summarizes the data from animal and clinical trials of MRgFUS treatment for bone metastases, with subsequent discussion of future directions for use of MRgFUS for treatment of osseous neoplasm.


Bone Metastasis Numerical Rating Scale Visual Analog Scale Radionuclide Therapy Bone Cancer Pain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Buckwalter JA, Brandser EA. Metastatic disease of the skeleton. Am Fam Physician. 1997;55(5):1761–8.PubMedGoogle Scholar
  2. 2.
    Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655–64.CrossRefPubMedGoogle Scholar
  3. 3.
    Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987;55:61–6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sabino MA, Mantyh PW. Pathophysiology of bone cancer pain. J Support Oncol. 2005;3(1):15–24.PubMedGoogle Scholar
  5. 5.
    Nielsen OS, Bentzen SM, Sandberg E, Gadeberg CC, Timothy AR. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiother Oncol. 1998;47(3):233–40.CrossRefPubMedGoogle Scholar
  6. 6.
    Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol. 1991;9(3):509–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93.CrossRefPubMedGoogle Scholar
  8. 8.
    Goblirsch MJ, Zwolak PP. Clohisy DR biology of bone cancer pain. Clin Cancer Res. 2006;12(Suppl 20):6231s–5.CrossRefPubMedGoogle Scholar
  9. 9.
    Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain. 2001;93:247–57.CrossRefPubMedGoogle Scholar
  10. 10.
    Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008;3(Suppl 3):S131–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ibrahim T, Flamini E, Mercatali L, Sacanna E, Serra P, Amadori D. Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer. 2010;116(6):1406–18.CrossRefPubMedGoogle Scholar
  12. 12.
    Casimiro S, Guise TA, Chirgwin J. The critical role of the bone microenvironment in cancer metastases. Mol Cell Endocrinol. 2009;310(1–2):71–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Kakonen SM, Mundy GR. Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer. 2003;97:834–9.CrossRefPubMedGoogle Scholar
  14. 14.
    von Moos R, Strasser F, Gillessen S, Zaugg K. Metastatic bone pain: treatment options with an emphasis on bisphosphonates. Support Care Cancer. 2008;16(10):1105.CrossRefGoogle Scholar
  15. 15.
    Cleeland CS, Ryan KM. Pain assessment: global use of the brief pain inventory. Ann Acad Med Singapore. 1994;23(2):129–38.PubMedGoogle Scholar
  16. 16.
    Chow E, et al. Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases. Radiother Oncol. 2001;61(1):77–82.CrossRefPubMedGoogle Scholar
  17. 17.
    Hartsell WF, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97(11):798–804.CrossRefPubMedGoogle Scholar
  18. 18.
    Serlin RC, et al. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995;61(2):277–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Veresciagina K, Ambrozaitis KV, Spakauskas B. The measurements of health-related quality-of-life and pain assessment in the preoperative patients with low back pain. Medicina (Kaunas). 2009;45(2):111–22.Google Scholar
  21. 21.
    Torrance GW, Feeny D, Furlong W. Visual analog scales: do they have a role in the measurement of preferences for health states? Med Decis Making. 2001;21(4):329–34.CrossRefPubMedGoogle Scholar
  22. 22.
    Diederich CJ, Hynynen K. Ultrasound technology for hyperthermia. Ultrasound Med Biol. 1999;25(6):871–87.CrossRefPubMedGoogle Scholar
  23. 23.
    Goetz MP, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol. 2004;22(2):300–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Cole DJ. A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol (R Coll Radiol). 1989;1(2):59–62.CrossRefGoogle Scholar
  25. 25.
    Gaze MN, et al. Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules. Radiother Oncol. 1997;45(2):109–16.CrossRefPubMedGoogle Scholar
  26. 26.
    Jeremic B, et al. A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys. 1998;42(1):161–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Konski A, Feigenberg S, Chow E. Palliative radiation therapy. Semin Oncol. 2005;32(2):156–64.CrossRefPubMedGoogle Scholar
  28. 28.
    Steenland E, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch bone metastasis study. Radiother Oncol. 1999;52(2):101–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Janjan NA. Radiation for bone metastases: conventional techniques and the role of systemic radiopharmaceuticals. Cancer. 1997;80:1628–45.CrossRefPubMedGoogle Scholar
  30. 30.
    Kashima M, Yamakado K, Takaki H, Kaminou T, Tanigawa N, Nakatsuka A, Takeda K. Radiofrequency ablation for the treatment of bone metastases from hepatocellular carcinoma. AJR Am J Roentgenol. 2010;194(2):536–41.CrossRefPubMedGoogle Scholar
  31. 31.
    Lewington VJ, McEwan AJ, Ackery DM, Bayly RJ, Keeling DH, Macleod PM, Porter AT, Zivanovic MA. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer. 1991;27(8):954–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, Fogelman I, Houston S, Fauser A, Fischer M, Wilkins D. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997;33:1583–91.CrossRefPubMedGoogle Scholar
  33. 33.
    Serafini AN, Klein JL, Wolff BG, Baum R, Chetanneau A, Pecking A, Fischman AJ, Hoover Jr HC, Wynant GE, Subramanian R, Goroff DK, Hanna Jr MG. Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99 m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies. J Clin Oncol. 1998;16:1574–81.CrossRefPubMedGoogle Scholar
  34. 34.
    Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, Kotler JA, Freeman LM, Olivier P. Quadramet 424Sm10/11 study group. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004;63:940–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Dalton JA, Youngblood R. Clinical application of the World health organization analgesic ladder. J Intraven Nurs. 2000;23(2):118–24.PubMedGoogle Scholar
  36. 36.
    Yuen KK, Shelley M, Sze WM, Wilt T, Mason MD. Bisphosphonates for advanced prostate cancer. Cochrane Database Syst Rev. 2006;18(4):CD006250.Google Scholar
  37. 37.
    Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev. Cochrane Database Syst Rev. 2005;20(3):CD003474.Google Scholar
  38. 38.
    Lipton A. Bone continuum of cancer. Am J Clin Oncol. 2010;33(3 Suppl):S1–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Coleman R, Gnant M. New results from the use of bisphosphonates in cancer patients. Curr Opin Support Palliat Care. 2009;3(3):213–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Sabharwal T, Katsanos K, Buy X, Gangi A. Image-guided ablation therapy of bone tumors. Semin Ultrasound CT MRI. 2009;30:78–90.CrossRefGoogle Scholar
  41. 41.
    Callstrom MR, Atwell TD, Charboneau JW, et al. Painful metastases involving bone: percutaneous image-guided cryoablation-prospective trial interim analysis. Radiology. 2006;241:572–80.CrossRefPubMedGoogle Scholar
  42. 42.
    Callstrom MR, Charboneau JW, Goetz MP, et al. Image guided ablation of painful metastatic bone tumours: a new and effective approach to a difficult problem. Skeletal Radiol. 2006;35:1–15.CrossRefPubMedGoogle Scholar
  43. 43.
    Nakatsuka A, Yamakado K, Takaki H, et al. Percutaneous radiofrequency ablation of painful spinal tumors adjacent to the spinal cord with real-time monitoring of spinal canal temperature: a prospective study. Cardiovasc Intervent Radiol. 2009;32:70–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Nakatsuka A, Yamakado K, Maeda M, et al. Radiofrequency ablation combined with bone cement injection for the treatment of bone malignancies. J Vasc Interv Radiol. 2004;15:707–12.CrossRefPubMedGoogle Scholar
  45. 45.
    Kodama H, Aikata H, Uka K, et al. Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma. Oncology. 2007;72:285–92.CrossRefPubMedGoogle Scholar
  46. 46.
    Kojima H, Tanigawa N, Kariya S, et al. Clinical assessment of percutaneous radiofrequency ablation for painful metastatic bone tumors. Cardiovasc Intervent Radiol. 2006;29:1022–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Grönemeyer DH, Schirp S, Gevargez A. Image-guided radiofrequency ablation of spinal tumors: preliminary experience with an expandable array electrode. Cancer J. 2002;8:33–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Fennessy FM, Tempany CM. MRI-guided focused ultrasound surgery of uterine leiomyomas. Acad Radiol. 2005;12(9):1158–66.CrossRefPubMedGoogle Scholar
  49. 49.
    Jolesz JA. 1996 RSNA Eugene P. Pendergrass New Horizons Lecture: Image-guided procedures and the operating room of the future. Radiology. 1997;204:601–12.CrossRefPubMedGoogle Scholar
  50. 50.
    Grimson WE, Kikinis R, Jolesz FA, et al. Image-guided surgery. Sci Am. 1999;280:62–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Jolesz FA. Interventional and intraoperative MRI: a general overview of the field. J Magn Reson Imaging. 1998;8:3–7.CrossRefPubMedGoogle Scholar
  52. 52.
    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;249(1):355–63.CrossRefPubMedGoogle Scholar
  53. 53.
    Jolesz FA. MRI-guided focused ultrasound surgery. Annu Rev Med. 2009;60:417–30.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kopelman D, Inbar Y, Hanannel A, Pfeffer RM, Dogadkin O, Freundlich D, Liberman B, Catane R. Magnetic resonance guided focused ultrasound surgery. Ablation of soft tissue at bone-muscle interface in a porcine model. Eur J Clin Invest. 2008;38(4):268–75.CrossRefPubMedGoogle Scholar
  55. 55.
    Ripamonti C, Fulfaro F. Malignant bone pain: pathophysiology and treatment. Curr Rev Pain. 2000;4(3):187–96.CrossRefPubMedGoogle Scholar
  56. 56.
    Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain. 1997;69(1–2):1–18.CrossRefPubMedGoogle Scholar
  57. 57.
    Catane R, Beck A, Inbar Y, Rabin T, Shabshin N, Hengst S, Pfeffer RM, Hanannel A, Dogadkin O, Liberman B, Kopelman D. MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases–preliminary clinical experience. Ann Oncol. 2007;18(1):163–7.CrossRefPubMedGoogle Scholar
  58. 58.
    Liberman B, Gianfelice D, Inbar Y, Beck A, Rabin T, Shabshin N, Chander G, Hengst S, Pfeffer R, Chechick A, Hanannel 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;16(1):140–6.CrossRefPubMedGoogle Scholar
  59. 59.
    Dewhirst MW, Vujaskovic Z, Jones E, Thrall D. Re-setting the biologic rationale for thermal therapy. Int J Hyperthermia. 2005;21(8):779–90.CrossRefPubMedGoogle Scholar
  60. 60.
    Horkan C, Dalal K, Coderre JA, Kiger JL, Dupuy DE, Signoretti S, Halpern EF, Goldberg SN. Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model. Radiology. 2005;235(1):81–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Jernberg A, Edgren MR, Lewensohn R, Wiksell H, Brahme A. Cellular effects of high-intensity focused continuous wave ultrasound alone and in combination with X-rays. Int J Radiat Biol. 2001;77(1):127–35.CrossRefPubMedGoogle Scholar
  62. 62.
    Raaphorst GP, Szekely JG. Thermal enhancement of cellular radiation damage: a review of complementary and synergistic effects. Scanning Microsc. 1988;2(1):513–35.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ronit Machtinger
    • 1
  • Fiona M. Fennessy
    • 2
  • Mark D. Hurwitz
    • 3
  1. 1.Department of Obstetrics and GynecologyBrigham and Women’s HospitalBostonUSA
  2. 2.Department of RadiationBrigham and Women’s HospitalBostonUSA
  3. 3.Department of Radiation OncologyDana-Farber/Brigham and Women’s Cancer CenterBostonUSA

Personalised recommendations