• Laura CampanacciEmail author
  • Flavio Fazioli


Bone metastatic disease is a major cause of pain and decreased quality of life in patients with cancer. In addition to systemic therapy and pain control with narcotic analgesics, standard local treatments include palliation with radiation therapy, surgery, embolization or focused ultrasound treatment. However 20–30% of patients do not respond to conventional treatments, increasing the interest in alternative therapies.

Electrochemotherapy (ECT) – a combination of high-voltage electric pulses and of an anticancer drug – has demonstrated high effectiveness in the treatment of cutaneous and subcutaneous tumours and proved to be successfully used in the treatment of tumours regardless of its histological origin. Because of its demonstrated efficacy in the treatment of cutaneous and subcutaneous tumours, its application deserves to be extended to the treatment of internal tumours. To advance electrochemotherapy to treating internal solid tumours, new technological developments enabled treatment of internal tumours in daily clinical practice. Preclinical studies and clinical trial demonstrated the feasibility and efficacy of electrochemotherapy for the treatment of bone metastases.

ECT should be considered a new feasible tool in the treatment of bone metastases in place or in combination with standard local treatments; further developments are required to extend the use of this technique to spine metastases.


Electroporation Electrochemotherapy Cancer treatment Treatment planning 


  1. 1.
    Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165–76.CrossRefPubMedGoogle Scholar
  2. 2.
    Jacofsky DJ, Frassica DA, Frassica FJ. Metastatic disease to bone. Hosp Physician. 2004;39:21–8.Google Scholar
  3. 3.
    Bickels J, Dadia S, Lidar Z. Surgical management of metastatic bone disease. J Bone Joint Surg Am. 2009;91(6):1503–16. (Review).CrossRefPubMedGoogle Scholar
  4. 4.
    Callstrom MR, Charboneau JW, Goetz MP, et al. Image-guided ablation of painful metastatic bone tumors: a new and effective approach to a difficult problem. Skelet Radiol. 2006;35:1–15.CrossRefGoogle Scholar
  5. 5.
    Culleton S, Kwok S, Chow E. Radiotherapy for pain. Clin Oncol. 2010;23:399–406.CrossRefGoogle Scholar
  6. 6.
    Jeremic B, Shibamoto Y, Acimovic L, 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;42:161–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy a systemic review of randomized trial. Clin Oncol (R Coll Radiol). 2003;15(6):345–52.CrossRefGoogle Scholar
  8. 8.
    Yang L, Du S. Efficacy and safety of zoledronic acid and pamidronate disodium in the treatment of malignant skeletal metastasis: a meta-analysis. Medicine (Baltimore). 2015;94(42):e1822.CrossRefGoogle Scholar
  9. 9.
    Mir LM, Belehradek M, Domenge C, et al. Electrochemotherapy, a new antitumor treatment: first clinical trial. C R Acad Sci III. 1991;313:613–8.PubMedGoogle Scholar
  10. 10.
    Mir L, Glass L, Sersa G, Teissie J, Domenge C, Miklavcic D, et al. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer. 1998;77:2336–42.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Belehradek M, Domenge C, Luboinski B, Orlowski S, Belehradek J, Mir LM. Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer. 1993;72:3694–700.CrossRefPubMedGoogle Scholar
  12. 12.
    Colombo GL, Di Matteo S, Mir LM. Cost-effectiveness analysis of electrochemotherapy with the Cliniporator™ vs other methods for the control and treatment of cutaneous and subcutaneous tumors. Ther Clin Risk Manag. 2008;4(2):541–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kotnik T, Pucihar G, Miklavcic D. Induced transmembrane voltage and its correlation with electroporation-mediated molecular transport. J Membr Biol. 2010;236:3–13.CrossRefPubMedGoogle Scholar
  14. 14.
    Li W, Fan Q, Ji Z, et al. The effects of irreversible electroporation (IRE) on nerves. PLoS One. 2011;6(4):e18831.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mali B, Jarm T, Corovic S, et al. The effect of electroporation pulses on functioning of the heart. Med Biol Eng Comput. 2008;46:745–57.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Maor E, Ivorra A, Leor J, Rubinsky B. The effect of irreversible electroporation on blood vessels. Technol Cancer Res Treat. 2007;6(4):307–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Horiuchi A, Nikaido T, Mitsushita J, et al. Enhancement of antitumor effect of bleomycin by low-voltage in vivo electroporation: a study of human uterine leiomyosarcomas in nude mice. Int J Cancer. 2000;88(4):640–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Marty M, Sersa G, Garbay JR, et al. Electrochemotherapy - an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European standard operating procedures of electrochemotherapy) study. EJC Suppl. 2006;4:3–13.CrossRefGoogle Scholar
  19. 19.
    Mali B, Jarm T, Snoj M, Sersa G, Miklavcic D. Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol. 2013;39(1):4–16.CrossRefPubMedGoogle Scholar
  20. 20.
    Agerholm-Larsen B, Iversen HK, Ibsen P, Moller JM, Mahmood F, Jensen KS, et al. Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. Cancer Res. 2011;71:3753–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Fini M, Tschon M, Ronchetti M, et al. Ablation of bone cells by electroporation. J Bone Joint Surg Br. 2010;92(11):1614–20.CrossRefPubMedGoogle Scholar
  22. 22.
    Fini M, Salamanna F, Parrilli A, Martini L, Cadossi M, Maglio M, Borsari V. Electrochemotherapy is effective in the treatment of rat bone metastases. Clin Exp Metastasis. 2013;30(8):1033–45.CrossRefPubMedGoogle Scholar
  23. 23.
    Tschon M, Salamanna F, Ronchetti M, Cavani F, Gasbarrini A, Boriani S, Fini M. Feasibility of electroporation in bone and in the surrounding clinically relevant structures: a preclinical investigation. Technol Cancer Res Treat. 2016;15(6):737–48.CrossRefPubMedGoogle Scholar
  24. 24.
    Campana LG, Mocellin S, Basso M, et al. Bleomycin-based electrochemotherapy: clinical outcome from a single institution’s experience with 52 patients. Ann Surg Oncol. 2009;16(1):191–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Sersa G, Jarm T, Kotnik T, et al. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Br J Cancer. 2008;98(2):388–98.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bianchi G, Campanacci L, Ronchetti M, Donati D. Electrochemotherapy in the treatment of bone metastases: a phase II trial. World J Surg. 2016;40(12):3088–94.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Miklavcic D, Beravs K, Semrov D, et al. The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys J. 1998;74:2152–8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Miklavcic D, Corovic S, Pucihar G, et al. Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. EJC Suppl. 2006;4:45–51.CrossRefGoogle Scholar
  29. 29.
    Miklavcic D, Snoj M, Zupanic A, et al. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomed Eng Online. 2010;9:10.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gasbarrini A, Campos WK, Campanacci L, Boriani S. Electrochemotherapy to metastatic spinal melanoma: a novel treatment of spinal metastasis? Spine. 2015;40(24):1340–6.CrossRefGoogle Scholar
  31. 31.
    Gruppo di Studio SIOT sulle Metastasi Ossee, coordinator A. Piccioli. Linee guida: trattamento delle metastasi ossee nello scheletro appendicolare. GIOT. 2014;40:1–15.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Oncological Orthopaedic DepartmentIstituto Ortopedico RizzoliBolognaItaly
  2. 2.Musculoskeletal Oncologic SurgeryIstituto nazionate Tumori Fondazione PascaleNaplesItaly

Personalised recommendations