Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Thermal ablation of tumours: biological mechanisms and advances in therapy

Abstract

Minimally invasive thermal ablation of tumours has become common since the advent of modern imaging. From the ablation of small, unresectable tumours to experimental therapies, percutaneous radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation have an increasing role in the treatment of solid neoplasms. This Opinion article examines the mechanisms of tumour cell death that are induced by the most common thermoablative techniques and discusses the rapidly developing areas of research in the field, including combinatorial ablation and immunotherapy, synergy with conventional chemotherapy and radiation, and the development of a new ablation modality in irreversible electroporation.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: The zones of hyperthermic ablation.
Figure 3: Mechanisms of cell death in cryoablation.
Figure 4: Potential immunotherapy targets that could be combined with ablation.

Similar content being viewed by others

References

  1. Tiong, L. & Maddern, G. J. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br. J. Surg. 98, 1210–1224 (2011).

    CAS  PubMed  Google Scholar 

  2. Ahmed, M., Brace, C. L., Lee, F. T. & Goldberg, S. N. Principles of and advances in percutaneous ablation. Radiology 258, 351–369 (2011).

    PubMed  Google Scholar 

  3. Pereira, P. L. Actual role of radiofrequency ablation of liver metastases. Eur. Radiol. 17, 2062–2070 (2007).

    PubMed  Google Scholar 

  4. Paulet, E. et al. Factors limiting complete tumor ablation by radiofrequency ablation. Cardiovasc. Interv. Radiol. 31, 107–115 (2008).

    Google Scholar 

  5. Haen, S. P., Pereira, P. L., Salih, H. R., Rammensee, H.-G. & Gouttefangeas, C. More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clin. Dev. Immunol. 2011, 1–19 (2011).

    Google Scholar 

  6. Kwan, K. G. & Matsumoto, E. D. Radiofrequency ablation and cryoablation of renal tumours. Curr. Oncol. 14, 34–38 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Davalos, R. V., Mir, L. M. & Rubinsky, B. Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 33, 223–231 (2005).

    CAS  PubMed  Google Scholar 

  8. Sánchez-Ortiz, R. F., Tannir, N., Ahrar, K. & Wood, C. G. Spontaneous regression of pulmonary metastases from renal cell carcinoma after radio frequency ablation of primary tumor: an in situ tumor vaccine? J. Urol. 170, 178–179 (2003).

    PubMed  Google Scholar 

  9. Kim, H., Park, B. K. & Kim, C. K. Spontaneous regression of pulmonary and adrenal metastases following percutaneous radiofrequency ablation of a recurrent renal cell carcinoma. Kor. J. Radiol. 9, 470–472 (2008).

    CAS  Google Scholar 

  10. Soanes, W. A., Ablin, R. J. & Gonder, M. J. Remission of metastatic lesions following cryosurgery in prostatic cancer: immunologic considerations. J. Urol. 104, 154–159 (1970).

    CAS  PubMed  Google Scholar 

  11. McGahan, J. P. et al. Hepatic ablation with use of radio-frequency electrocautery in the animal model. J. Vasc. Interv. Radiol. 3, 291–297 (1992).

    CAS  PubMed  Google Scholar 

  12. Formenti, S. C. & Demaria, S. Systemic effects of local radiotherapy. Lancet Oncol. 10, 718–726 (2009).

    PubMed  PubMed Central  Google Scholar 

  13. Nikfarjam, M., Muralidharan, V. & Christophi, C. Mechanisms of focal heat destruction of liver tumors. J. Surg. Res. 127, 208–223 (2005).

    PubMed  Google Scholar 

  14. Fajardo, L. F., Egbert, B., Marmor, J. & Hahn, G. M. Effects of hyperthermia in a malignant tumor. Cancer 45, 613–623 (1980).

    CAS  PubMed  Google Scholar 

  15. Willis, W. T., Jackman, M. R., Bizeau, M. E., Pagliassotti, M. J. & Hazel, J. R. Hyperthermia impairs liver mitochondrial function in vitro. Am. J. Physiol. 278, R1240–R1246 (2000).

    CAS  Google Scholar 

  16. Wheatley, D. N., Kerr, C. & Gregory, D. W. Heat-induced damage to HeLa-S3 cells: correlation of viability, permeability, osmosensitivity, phase-contrast light-, scanning electron- and transmission electron-microscopical findings. Int. J. Hyperthermia. 5, 145–162 (1989).

    CAS  PubMed  Google Scholar 

  17. Warters, R. L. & Roti Roti, J. L. Hyperthermia and the Cell Nucleus. Radiat. Res. 92, 458–462 (1982).

    CAS  PubMed  Google Scholar 

  18. Dupuy, D. E. et al. Radiofrequency ablation followed by conventional radiotherapy for medically inoperable stage I non-small cell lung cancer. Chest 129, 738–745 (2006).

    PubMed  Google Scholar 

  19. Hines-Peralta, A. et al. Improved tumor destruction with arsenic trioxide and radiofrequency ablation in three animal models. Radiology 240, 82–89 (2006).

    PubMed  Google Scholar 

  20. Wright, A. S., Sampson, L. A., Warner, T. F., Mahvi, D. M. & Lee, F. T. Radiofrequency versus microwave ablation in a hepatic porcine model. Radiology 236, 132–139 (2005).

    PubMed  Google Scholar 

  21. Muralidharan, V., Malcontenti-Wilson, C. & Christophi, C. Effect of blood flow occlusion on laser hyperthermia for liver metastases. J. Surg. Res. 103, 165–174 (2002).

    CAS  PubMed  Google Scholar 

  22. Whelan, W. M., Wyman, D. R. & Wilson, B. C. Investigations of large vessel cooling during interstitial laser heating. Med. Phys. 22, 105–115 (1995).

    CAS  PubMed  Google Scholar 

  23. Dromi, S. A. et al. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 251, 58–66 (2009).

    PubMed  PubMed Central  Google Scholar 

  24. Wissniowski, T. T. et al. Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res. 63, 6496–6500 (2003).

    CAS  PubMed  Google Scholar 

  25. Zerbini, A. et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology 138, 1931–1942 (2010).

    CAS  PubMed  Google Scholar 

  26. Nijkamp, M. W. et al. Radiofrequency ablation of colorectal liver metastases induces an inflammatory response in distant hepatic metastases but not in local accelerated outgrowth. J. Surg. Oncol. 101, 551–556 (2010).

    PubMed  Google Scholar 

  27. Rughetti, A. et al. Modulation of blood circulating immune cells by radiofrequency tumor ablation. J. Exp. Clin. Cancer Res. 22, 247–250 (2003).

    CAS  PubMed  Google Scholar 

  28. Ali, M. Y. et al. Activation of dendritic cells by local ablation of hepatocellular carcinoma. J. Hepatol. 43, 817–822 (2005).

    CAS  PubMed  Google Scholar 

  29. Fietta, A. M. et al. Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+ T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer. Hum. Immunol. 70, 477–486 (2009).

    CAS  PubMed  Google Scholar 

  30. den Brok, M. H. M. G. M. et al. In situ tumor ablation creates an antigen source for the generation of antitumor immunity. Cancer Res. 64, 4024–4029 (2004).

    CAS  PubMed  Google Scholar 

  31. Sabel, M. S. Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 58, 1–11 (2009).

    CAS  PubMed  Google Scholar 

  32. Erinjeri, J. P. et al. Image-guided thermal ablation of tumors increases the plasma level of Interleukin-6 and Interleukin-10. J. Vasc. Interv. Radiol. 24, 1105–1112 (2013).

    PubMed  PubMed Central  Google Scholar 

  33. Ahmad, F. et al. Changes in interleukin-1β and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections. Am. J. Surg. 200, 500–506 (2010).

    CAS  PubMed  Google Scholar 

  34. Teng, L.-S., Jin, K.-T., Han, N. & Cao, J. Radiofrequency ablation, heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers: a minireview. Hepatobiliary Pancreat. Dis. Int. 9, 361–365 (2010).

    Google Scholar 

  35. Schueller, G. et al. Heat shock protein expression induced by percutaneous radiofrequency ablation of hepatocellular carcinoma in vivo. Int. J. Oncol. 24, 609–613 (2004).

    CAS  PubMed  Google Scholar 

  36. Rai, R. et al. Study of apoptosis and heat shock protein (HSP) expression in hepatocytes following radiofrequency ablation (RFA). J. Surg. Res. 129, 147–151 (2005).

    CAS  PubMed  Google Scholar 

  37. Solazzo, S. A. et al. Liposomal doxorubicin increases radiofrequency ablation-induced tumor destruction by increasing cellular oxidative and nitrative and stress accelerating apoptotic pathways. Radiology. 255, 62–74 (2010).

    PubMed  PubMed Central  Google Scholar 

  38. Yang, W.-L. et al. Heat shock protein 70 is induced in mouse human colon tumor xenografts after sublethal radiofrequency ablation. Ann. Surg. Oncol. 11, 399–406 (2004).

    PubMed  Google Scholar 

  39. Basu, S., Binder, R. J., Suto, R., Anderson, K. M. & Srivastava, P. K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int. Immunol. 12, 1539–1546 (2000).

    CAS  PubMed  Google Scholar 

  40. Garrido, C., Brunet, M., Didelot, C., Schmitt, E. & Kroemer, G. Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5, 2592–2601 (2006).

    CAS  PubMed  Google Scholar 

  41. Chen, T., Guo, J., Han, C., Yang, M. & Cao, X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J. Immunol. 182, 1449–1459 (2009).

    CAS  PubMed  Google Scholar 

  42. Figueiredo, C. et al. Heat shock protein 70 (HSP70) induces cytotoxicity of T-helper cells. Blood 113, 3008–3016 (2009).

    CAS  PubMed  Google Scholar 

  43. den Brok, M. H. M. G. M. et al. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. Br. J. Cancer 95, 896–905 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Arnold, D., Faath, S., Rammensee, H. & Schild, H. Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96. J. Exp. Med. 182, 885–889 (1995).

    CAS  PubMed  Google Scholar 

  45. Srivastava, P. Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu. Rev. Immunol. 20, 395–425 (2002).

    CAS  PubMed  Google Scholar 

  46. Haen, S. P. et al. Elevated serum levels of heat shock protein 70 can be detected after radiofrequency ablation. Cell Stress Chaperones 16, 495–504 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Schueller, G. et al. Expression of heat shock proteins in human hepatocellular carcinoma after radiofrequency ablation in an animal model. Oncol. Rep. 12, 495–499 (2004).

    CAS  PubMed  Google Scholar 

  48. Hiroishi, K. et al. Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma. J. Gastroenterol. 45, 451–458 (2010).

    CAS  PubMed  Google Scholar 

  49. Lubner, M. G., Brace, C. L., Hinshaw, J. L. & Lee, F. T. Microwave tumor ablation: mechanism of action, clinical results and devices. J. Vasc. Interv. Radiol. 21, S192–S203 (2010).

    PubMed  PubMed Central  Google Scholar 

  50. Wright, A. S., Lee, F. T. & Mahvi, D. M. Hepatic microwave ablation with multiple antennae results in synergistically larger zones of coagulation necrosis. Ann. Surg. Oncol. 10, 275–283 (2003).

    PubMed  Google Scholar 

  51. Ahmad, F. et al. Renal effects of microwave ablation compared with radiofrequency, cryotherapy and surgical resection at different volumes of the liver treated. Liver Int. 30, 1305–1314 (2010).

    PubMed  Google Scholar 

  52. Dong, B. W. et al. Sequential pathological and immunologic analysis of percutaneous microwave coagulation therapy of hepatocellular carcinoma. Int. J. Hyperthermia. 19, 119–133 (2003).

    CAS  PubMed  Google Scholar 

  53. Mala, T. Cryoablation of liver tumours — a review of mechanisms, techniques and clinical outcome. Minim. Invasive Ther. Allied Technol. 15, 9–17 (2006).

    Google Scholar 

  54. Mala, T. et al. Magnetic resonance imaging-estimated three-dimensional temperature distribution in liver cryolesions: a study of cryolesion characteristics assumed necessary for tumor ablation. Cryobiology 43, 268–275 (2001).

    CAS  PubMed  Google Scholar 

  55. Hoffmann, N. E. & Bischof, J. C. The cryobiology of cryosurgical injury. Urology 60, 40–49 (2002).

    PubMed  Google Scholar 

  56. Lovelock, J. E. The haemolysis of human red blood-cells by freezing and thawing. Biochim. Biophys. Acta. 10, 414–426 (1953).

    CAS  PubMed  Google Scholar 

  57. Baust, J. G. & Gage, A. A. The molecular basis of cryosurgery. BJU Int. 95, 1187–1191 (2005).

    PubMed  Google Scholar 

  58. Hanai, A., Yang, W. L. & Ravikumar, T. S. Induction of apoptosis in human colon carcinoma cells HT29 by sublethal cryo-injury: mediation by cytochrome c release. Int. J. Cancer 93, 526–533 (2001).

    CAS  PubMed  Google Scholar 

  59. Yang, W.-L., Addona, T., Nair, D. G., Qi, L. & Ravikumar, T. S. Apoptosis induced by cryo-injury in human colorectal cancer cells is associated with mitochondrial dysfunction. Int. J. Cancer 103, 360–369 (2003).

    CAS  PubMed  Google Scholar 

  60. Alblin, R. J., Soanes, W. A. & Gonder, M. J. Prospects for cryo-immunotherapy in cases of metastasizing carcinoma of the prostate. Cryobiology 8, 271–279 (1971).

    CAS  PubMed  Google Scholar 

  61. Gursel, E., Roberts, M. & Veenema, R. J. Regression of prostatic cancer following sequential cryotherapy to the prostate. J. Urol. 108, 928–932 (1972).

    CAS  PubMed  Google Scholar 

  62. Ablin, R. J. Cryosurgery of the rabbit prostate. Comparison of the immune response of immature and mature bucks. Cryobiology 11, 416–422 (1974).

    CAS  PubMed  Google Scholar 

  63. Ablin, R. et al. Cryosurgery of the monkey (macaque) prostate. I. Humoral immunologic responsiveness following cryostimulation. Cryobiology 13, 47–53 (1976).

    CAS  PubMed  Google Scholar 

  64. Ablin, R. J. & Reddy, K. P. Cryosurgery of the monkey (macaque) prostate. II. Apparent immunopathologic alterations following cryostimulation. Cryobiology 14, 205–214 (1977).

    CAS  PubMed  Google Scholar 

  65. Jansen, M. C. et al. Cryoablation induces greater inflammatory and coagulative responses than radiofrequency ablation or laser induced thermotherapy in a rat liver model. Surgery 147, 686–695 (2010).

    PubMed  Google Scholar 

  66. Chapman, W. C. et al. Hepatic cryoablation, but not radiofrequency ablation, results in lung inflammation. Ann. Surg. 231, 752–761 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Ravindranath, M. H. et al. Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM. Cryobiology 45, 10–21 (2002).

    CAS  PubMed  Google Scholar 

  68. Gravante, G., Sconocchia, G., Ong, S. L., Dennison, A. R. & Lloyd, D. M. Immunoregulatory effects of liver ablation therapies for the treatment of primary and metastatic liver malignancies. Liver Int. 29, 18–24 (2009).

    CAS  PubMed  Google Scholar 

  69. Chapman, W. C. et al. Hepatic cryoablation-induced acute lung injury. Arch. Surg. 135, 667–673 (2013).

    Google Scholar 

  70. Blackwell, T. S. et al. Acute lung injury after hepatic cryoablation: correlation with NF-κB activation and cytokine production. Surgery 126, 518–526 (1999).

    CAS  PubMed  Google Scholar 

  71. Gazzaniga, S. et al. Inflammatory changes after cryosurgery-induced necrosis in human melanoma xenografted in nude mice. J. Invest. Dermatol. 116, 664–671 (2001).

    CAS  PubMed  Google Scholar 

  72. Sabel, M. S. et al. Immunologic response to cryoablation of breast cancer. Breast Cancer Res. Treat. 90, 97–104 (2005).

    CAS  PubMed  Google Scholar 

  73. Blackwood, C. E. & Cooper, I. S. Response of experimental tumor systems to cryosurgery. Cryobiology 9, 508–515 (1972).

    CAS  PubMed  Google Scholar 

  74. Urano, M., Tanaka, C., Sugiyama, Y., Miya, K. & Saji, S. Antitumor effects of residual tumor after cryoablation: the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model. Cryobiology 46, 238–245 (2003).

    CAS  PubMed  Google Scholar 

  75. Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nature Med. 5, 1249–1255 (1999).

    CAS  PubMed  Google Scholar 

  76. Sauter, B. et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191, 423–434 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Seifert, J. K. et al. Large volume hepatic freezing: association with significant release of the cytokines interleukin-6 and tumor necrosis factor a in a rat model. World J. Surg. 26, 1333–1341 (2002).

    PubMed  Google Scholar 

  78. Wing, M. G., Rogers, K., Jacob, G. & Rees, R. C. Characterisation of suppressor cells generated following cryosurgery of an HSV-2-induced fibrosarcoma. Cancer Immunol. Immunother. 26, 169–175 (1988).

    CAS  PubMed  Google Scholar 

  79. Yamashita, T. et al. Enhanced tumor metastases in rats following cryosurgery of primary tumor. Gann 73, 222–228 (1982).

    CAS  PubMed  Google Scholar 

  80. Sabel, M. S., Su, G., Griffith, K. A. & Chang, A. E. Rate of freeze alters the immunologic response after cryoablation of breast cancer. Ann. Surg. Oncol. 17, 1187–1193 (2010).

    PubMed  Google Scholar 

  81. Yang, W. et al. Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment. Hepatol. Res. 39, 231–240 (2009).

    CAS  PubMed  Google Scholar 

  82. Peng, Z.-W. et al. Radiofrequency ablation as first-line treatment for small solitary hepatocellular carcinoma: long-term results. Eur. J. Surg. Oncol. 36, 1054–1060 (2010).

    PubMed  Google Scholar 

  83. Yang, P., Liang, M., Zhang, Y. & Shen, B. Clinical application of a combination therapy of lentinan, multi-electrode RFA and TACE in HCC. Adv. Ther. 25, 787–794 (2008).

    CAS  PubMed  Google Scholar 

  84. Morimoto, M. et al. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer 116, 5452–5460 (2010).

    PubMed  Google Scholar 

  85. Hakime, A. et al. Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy: study in mice. Radiology 244, 464–470 (2007).

    PubMed  Google Scholar 

  86. Goldberg, S. N., Hahn, P. F., Halpern, E. F., Fogle, R. M. & Gazelle, G. S. Radio-frequency tissue ablation: effect of pharmacologic modulation of blood flow on coagulation diameter. Radiology 209, 761–767 (1998).

    CAS  PubMed  Google Scholar 

  87. Horkan, C. et al. Radiofrequency ablation: effect of pharmacologic modulation of hepatic and renal blood flow on coagulation diameter in a VX2 tumor model. J. Vasc. Interv. Radiol. 15, 269–274 (2004).

    PubMed  Google Scholar 

  88. Machlenkin, A. et al. Combined dendritic cell cryotherapy of tumor induces systemic antimetastatic immunity. Clin. Cancer Res. 11, 4955–4961 (2005).

    CAS  PubMed  Google Scholar 

  89. den Brok, M. H. M. G. M. et al. Synergy between in situ cryoablation and TLR9 stimulation results in a highly effective in vivo dendritic cell vaccine. Cancer Res. 66, 7285–7292 (2006).

    CAS  PubMed  Google Scholar 

  90. Redondo, P. et al. Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions. J. Invest. Dermatol. 127, 1673–1680 (2007).

    CAS  PubMed  Google Scholar 

  91. Nierkens, S. et al. Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice. PLoS ONE 4, e8368 (2009).

    PubMed  PubMed Central  Google Scholar 

  92. Waitz, R. et al. Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy. Cancer Res. 72, 430–439 (2012).

    CAS  PubMed  Google Scholar 

  93. Sabel, M. S., Arora, A., Su, G. & Chang, A. E. Adoptive immunotherapy of breast cancer with lymph node cells primed by cryoablation of the primary tumor. Cryobiology 53, 360–366 (2006).

    CAS  PubMed  Google Scholar 

  94. Yang, W. et al. Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat model? Radiology 257, 685–696 (2010).

    PubMed  PubMed Central  Google Scholar 

  95. Yang, W. et al. Radiofrequency ablation combined with liposomal quercetin to increase tumor destruction by modulation of heat shock protein production in a small animal model. Int. J. Hyperthermia 27, 527–538 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Goldberg, S. N. et al. Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intratumoral doxorubicin injection in a rat breast tumor model. Radiology 220, 420–427 (2001).

    CAS  PubMed  Google Scholar 

  97. Goldberg, S. N. et al. Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model. Radiology 222, 797–804 (2002).

    PubMed  Google Scholar 

  98. Goldberg, S. N. et al. Radiofrequency ablation of hepatic tumors: increased tumor destruction with adjuvant liposomal doxorubicin therapy. AJR Am. J. Roentgenol. 179, 93–101 (2002).

    PubMed  Google Scholar 

  99. Lasic, D. D. & Papahadjopoulos, D. Liposomes revisited. Science 267, 1275–1276 (1995).

    CAS  PubMed  Google Scholar 

  100. Ranson, M., Howell, A., Cheeseman, S. & Margison, J. Liposomal drug delivery. Cancer Treat. Rev. 22, 366–379 (1996).

    Google Scholar 

  101. Chen, Q. et al. Tumor microvascular permeability is a key determinant for antivascular effects of doxorubicin encapsulated in a temperature sensitive liposome. Int. J. Hyperthermia 24, 475–482 (2008).

    PubMed  PubMed Central  Google Scholar 

  102. Kong, G. et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res. 60, 6950–6957 (2000).

    CAS  PubMed  Google Scholar 

  103. Poon, R. T. & Borys, N. Lyso-thermosensitive liposomal doxorubicin: an adjuvant to increase the cure rate of radiofrequency ablation in liver cancer. Futur. Oncol. 7, 937–945 (2011).

    CAS  Google Scholar 

  104. Solazzo, S. et al. RF ablation with adjuvant therapy: comparison of external beam radiation and liposomal doxorubicin on ablation efficacy in an animal tumor model. Int. J. Hyperthermia 24, 560–567 (2008).

    CAS  PubMed  Google Scholar 

  105. Horkan, C. et al. Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model. Radiology 235, 81–88 (2005).

    PubMed  Google Scholar 

  106. Chan, M., Dupuy, D., Mayo-Smith, W., Ng, T. & DiPetrillo, T. Combined radiofrequency ablation and high-dose rate brachytherapy for early-stage non-small-cell lung cancer. Brachytherapy 10, 253–259 (2011).

    PubMed  Google Scholar 

  107. Grieco, C. A. et al. Percutaneous image-guided thermal ablation and radiation therapy: outcomes of combined treatment for 41 patients with inoperable stage I/II non-small-cell lung cancer. J. Vasc. Interv. Radiol. 17, 1117–1124 (2006).

    PubMed  Google Scholar 

  108. Onik, G., Mikus, P. & Rubinsky, B. Irreversible electroporation: implications for prostate ablation. Technol. Cancer Res. Treat. 6, 295–300 (2007).

    PubMed  Google Scholar 

  109. Okino, M. & Mohri, H. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J. Cancer Res. 78, 1319–1321 (1987).

    CAS  PubMed  Google Scholar 

  110. Rubinsky, B., Onik, G. & Mikus, P. Irreversible electroporation: a new ablation modality — clinical implications. Technol. Cancer Res. Treat. 6, 37–48 (2007).

    PubMed  Google Scholar 

  111. Faroja, M. et al. Irreversible electroporation ablation: is all the damage nonthermal? Radiology 266, 462–470 (2013).

    PubMed  Google Scholar 

  112. Srimathveeravalli, G. et al. Evaluation of an endorectal electrode for performing focused irreversible electroporation ablations in the swine rectum. J. Vasc. Interv. Radiol. 24, 1249–1256 (2013).

    PubMed  Google Scholar 

  113. Palucka, K. & Banchereau, J. Cancer immunotherapy via dendritic cells. Nature Rev. Cancer 12, 265–277 (2013).

    Google Scholar 

  114. Hamamoto, S. et al. Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits. Radiology 267, 405–413 (2013).

    PubMed  Google Scholar 

  115. Johnson, E. E. et al. Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma. Clin. Cancer Res. 15, 4875–4884 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Bovie, W. T. & Cushing, H. Electrosurgery as an aid to the removal of intracranial tumors with a preliminary note on a new surgical-current generator. Surg. Gynecol. Obs. 47, 751–784 (1928).

    Google Scholar 

  117. Lynn, J. G., Zwemer, R. L., Chick, A. J. & Miller, A. E. A new method for the generation and use of focused ultrasound in experimental biology. J. Gen. Physiol. 26, 179–193 (1942).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Gage, A. A. & Baust, J. Mechanisms of tissue injury in cryosurgery. Cryobiology 37, 171–186 (1998).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Damian E. Dupuy.

Ethics declarations

Competing interests

Grant Support from NeuWave Medical, Madison, Wisconsin, USA (D.E.D.). Consultant for BSD Medical, Salt Lake City, Utah, USA, and Covidien, Boulder Colorado (D.E.D.). Board of directors for BSD Medical (D.E.D.). K.F.C. declares no competing interests.

PowerPoint slides

Glossary

Acoustic energy

The energy that is generated by sound waves or oscillations in pressure.

Anergy

A form of T cell or B cell inactivation in which the cell remains alive but cannot be activated to execute an immune response. Anergy is a reversible state.

Brachytherapy

The implantation of radioactive pellets, which are approximately the size of a grain of rice, into the tissue that is being treated for cancer.

Clonal deletion

Elimination of T cells or B cells that have a high avidity for self antigens, either by negative selection during lymphocyte development or by FAS ligand-mediated destruction in the peripheral blood.

Coagulative necrosis

A form of tissue necrosis in which injury denatures structural proteins and enzymes, thereby prohibiting proteolysis of dead cells. Tissue architecture is preserved for days and necrotic debris is ultimately removed by infiltrating leukocytes.

Impedance

The effective resistance of an electric circuit.

Ischaemia

A reduced or lack of blood flow.

Lipiodol

Iodized poppyseed oil, which has been used for more than a century as a radiographic contrast agent.

Nitrosative stress

Inflammation and damage caused by reactive nitrogen species.

Pathogen-associated molecular pattern

(PAMP). A highly conserved structural motif that is commonly found on microorganisms. PAMPs include sugars, proteins, lipids and nucleic acids that are all recognized by the innate immune system.

Percutaneous

Pertaining to a procedure that is carried out through the skin.

Regulatory T cells

(TReg cells). A subset of T cells that display CD25 and that can inhibit CD4+ and CD8+ T cells. TReg cells express the transcription regulator forkhead box protein P3 (FOXP3), the lack of which predisposes to autoimmune diseases.

Three-dimensional radiotherapy

The application of radiation beams that are shaped to match the tumour to more precisely target it.

Transarterial chemoembolization

A procedure whereby chemotherapy is injected directly into the arterial supply of the tumour, and embolic agents are administered that cut off its blood supply.

Trocar-type probes

Surgical instruments with a three-sided cutting point enclosed in a hollow cylinder that is used to place other devices into the blood vessel or body cavity that it enters.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, K., Dupuy, D. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer 14, 199–208 (2014). https://doi.org/10.1038/nrc3672

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3672

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer