Hyperthemia & Cancer Treatment in Canada
What is Hyperthermia treatment?
Hyperthermia treatment is a common oncology treatment performed in Europe that heats tumors to fever temperatures inciting changes in the tumor to make it susceptible to destruction. This treatment is available in Winnipeg, Canada at the Centre for Natural Pain Solutions. German oncologists are trained in alternative therapies & this is why it is often recommended. However, this is not the case in North America. However, numerous studies show tremendous benefits to cancer patients. Over 100,000 hyperthermia treatments per year with the OncoTherm hyperthermia device are provided across the world.
Which cancers show benefit from hyperthermia treatment?
Graph showing increased benefit of addition of hyperthermia treatment to chemotherapy & radiation. (From Oncothemia; Loco-regional hyperthermia with Oncothermia Studies high-tech medicine.)
What are the types of Hyperthermia treatment?
Loco-Regional Hyperthermia (LRHT) generates heat within a localized area of the body, such as a tumour. Using a lower frequency of 13.56 MHz, even deep tumours can be treated1. This type of hyperthermia treatment uses a goal temperature of 41-45 °C and lasts approximately 1 hr. Nonetheless, using a radiant infrared device, hyperthermia can be stimulated in the whole body of a patient (i.e. Whole Body Hyperthermia or WBHT). However, the target temperature is lower than LRHT and within the fever-range of 38.5-40.5 °C1.
Loco-Regional Hyperthermia with Oncotherm EHY-2000 device. One of the world’s most advanced hyperthermia machines available at Centre for Natural Pain Solutions, Winnipeg, Canada.
How does Hyperthermia work?
With LRHT, most of the body remains at the average core temperature with just the tumour increasing in temperature. In this way, our bodies act as a sink for the heat to funnel into from the tumour2. In heating the whole body, WBHT (Whole-body hyperthermia), on the other hand, drives heat into the tumour. Largely, the body attempts to reach a temperature balance (i.e. homeostasis) during both hyperthermia treatments through vasodilation, or an increase in the size of our blood vessels.
What does Hyperthermia do to Cancer?
Blood Flow and Metabolism
Both treatments, LRHT and WBHT, increase blood flow, capillary filtration, capillary pressure and oxygen delivery2. However, an increase in temperature changes the structure and chemical bonds of molecules within cells. As such, an increase of heat also shifts cells into a state of high metabolic demand. Even with an increase of such demands in tumours, the surrounding intact tissue still transports the same quantity of nutrients2. With an unmet need for molecules such as glucose, the tumour is forced to use all of its energy stores. Subsequently, the cancer lesion starves and shrinks.
As levels of energy molecules like ATP decrease, lactic acids build up and decreases pH in tumour cells under hyperthermia treatment2,3. Furthermore, DNA replication slows or potentially stops in cells under the stress of high temperatures2,4,5. A lack of ATP also induces an imbalance of ions within these tumour cells2,6.
Blood Flow and Immune Response
Increased blood flow brings immune cells, such as phagocytes, to tumour sites. Likewise, antigen-presenting cells (APCs) will display tumour antigens on their surface and on the surface of the tumor cells2,7. APCs will also secrete these antigens to circulate in extracellular fluid2,8. All these processes simultaneously initiate an immune response against the tumour2,3,9.
Fever-like increases in temperature to an area with cancer will also break tumour cells down2,10. By damaging the cell membrane of tumours, damage-associated molecular patterns (DAMPS) are exposed. These DAMPS then trigger our immune system to recognize the presence of the cancer. Cells of our immune system, such as natural killer cells and dendritic cells, will recognize and attack these heat-damaged tumour cells10. Eventually, immune cells will stimulate a process called “apoptosis” or a controlled cell death of the tumour.
Hyperthermia also dilutes the cytoplasm, which thereby, increases pressure inside tumour cells, suppresses cell division, and stops DNA replication2. Much like what we see when heat damages cell membranes, heat-induced dilution of the cytoplasm also activates apoptosis by for example, turning on “death receptors.”
Blood Flow and Heat Proteins
During times of high body temperatures, the expression of specific heat shock proteins, also called chaperone proteins (ex: HSP70), is increased2. While some of these chaperone proteins do not suppress tumours, HSP70 specifically activates mediators for apoptosis as well as stimulates immune responses2,9. Interestingly, these proteins also turn on the p53 tumor suppressor pathway2,11.
Cell Migration and the Bystander Effect
By decreasing the motility of tumour cells, hyperthermia treatment reduces the risk of tumour cells migrating to other areas of the body2,12. Likewise, a study in mice observed the “abscopal” or bystander effect in tumours under hyperthermia treatment2,13. That is to say, when one tumour in the body was treated with hyperthermia and immune therapy was administered systematically, tumours in other parts of the body also became suppressed2,14.
Ultimately, hyperthermia assists our body’s feedback loops to balance the processes of2:
- Cell metabolism
- Cell death
- Cell division
- Immune response
- Heat protein expression
- Cell migration
Can Hyperthermia be combined with other forms of treatment?
Yes! Hyperthermia can be combined with chemotherapy and/or radiotherapy, as well as naturopathic treatment modalities, to increase their effectiveness as well as reduce the potential for tumor resistance1,2. As previously mentioned, hyperthermia also stimulates apoptosis in tumour cells. In this way, the cancer cells become more susceptible to cancer treatments such as chemotherapy and radiotherapy. However, hyperthermia also stops cell division, which increases the capacity of cancer treatments to work on these tissues1,2.
Hyperthermia-induced vasodilation increases the transport of drugs that are administered systemically. In particular, this increase in drug delivery increases the effectiveness of chemotherapy2,15,16. In fact, chemotherapy combined with hyperthermia reduces the overall effect of the drugs on the body because the drug targets itself into the tumour cells. Furthermore, lower doses of chemotherapy may be used in some cases when combined with hyperthermia2,17,18.
In the same way, increased vasodilation also increases the effect of radiotherapies2. By increasing the concentration of oxygen in the tissues, tumours become more sensitive to ionizing radiation2,18. Increased heat in tumour cells also reduces the expression of DNA-dependent protein-kinase, which further sensitizes tumours to radiation2,20.
Nonetheless, surgical treatments also benefit from hyperthermia2. By increasing temperature, blood vessel formation is reduced and heat becomes trapped inside the tumour. This heat treated tumour not only reduces in size but also becomes more prominent for surgical removal2,21. Hyperthermia can also be used during the surgery to improve the result of the treatment2,22,23. Even after surgical removal, hyperthermia has also been found to prevent relapse and metastasis of tumours2,24.
Recent evidence has shown that Hyperthermia can be combined gene-therapy in specific cancers, such as advanced breast cancer2,25. In particular, the expression of genes during heat treatment are effective, such as promoters of heat shock proteins26.
- Hormone therapies27,28
- Enzyme therapies28
- Photodynamic therapy29
- Immune therapy31
- IV vitamin C33
- IV DCA & ALA is used at our clinic & others along with hyperthermia treatments
- Other supportive therapies32
Can hyperthermia be used on it’s own?
Some studies show benefit of hyperthermia as a monotherapy in the treatment of some cancers including colorectal cancer, pancreatic cancer, lung cancer, ovarian cancer, stomach cancer, renal carcinoma, sarcoma & adenoid cystic carcinoma. 71
What kind of cancer patients can use Hyperthermia?
Any patient who:
- Wishes to add benefit to current treatment including naturopathic treatment, chemotherapy treatments, radiation treatments & surgery2,32
- Has an inoperable lesion2
- Is radio-resistant2
- Is chemo-resistant (refractory)2
- Has improper blood-counts2
- Has/or is at risk of liver-failure2
- Has/or is at risk of Kidney failure2
- Is looking for palliative care to increase in quality of life, including pain-reduction2,34
- Is in terminal phase2,35,36
- Has a weak immune-system and is looking for immune support2,37
Which cancers can be treated with Hyperthermia?
Hyperthermia is effective in the treatment of the following cancers:
- Bladder cancer38
- Brain cancer2,39,40,41,42,43,44,45,46,47,48,49,50,51
- Breast cancer38,52,53,54,55
- Cervical cancer56,57
- Colorectal cancer58
- Esophageal cancer59
- Liver cancer58
- Local lymphomas60
- Lung cancer61,62,63,64,65
- Ovarian cancer66
- Pancreatic cancer2,67,68
- Skin cancer70
- Stomach cancer71
1 Parmar G. 2016. A retrospective assessment: an integrative naturopathic oncology approach including loco-regional and fever-range whole body hyperthermia [PowerPoint slides]. Retrieved from https://www.integratedhealthclinic.com/assets/ourPublications/Habib -%20Parmar%20hyperthermia%20issue%2030.pdf
2 Szasz, A., Iluri, N. and Szasz, O. (2013) Local Hyperthermia in Oncology—To Choose or not to Choose? In: Huilgol, N., Ed., Hyperthermia, InTech, Winchester, 1-82
3 Vaupel, P. W. and Kelleher, D. K. (1996) Metabolic status and reaction to heat of normal and tumor tissue, In: Seegenschmiedt MH., Fessenden P., Vernon CC. (Eds.) Thermo-radiotherapy and Thermo-chemotherapy, Vol. 1. Biology, physiology and physics, Springer Verlag, Berlin Heidelberg, pp. 157-176
4 Keszler, G., Csapo, Z., and Spasokoutskaja, T. et al. (2000) Hyperthermy increase the phosporylation of deoxycytidine in the membrane phospholipid precursors and decrease its incorporation into DNA. Adv Exper Med Biol 486:333-337
5 Dikomey, E. and Franzke, J. (1992) Effect of heat on induction and repair of DNA strand breaks in X-irradiated CHO cells. Int J Radiat Biol 61(2):221-233
6 Kabakov, A. E. and Gabai, V. L. (1997) Heat Shock Proteins and cytoprotection: ATP-deprived mammalian cells. (Series: Molecular Biology Intelligence Unit), Springer Verlag, New York, Berlin, Heidelberg)
7 Srivastava, P. K., DeLeo, A. B., and Old, L. J. (1986) Tumor Rejection Antigens of Chemically Induced Tumors of Inbred Mice. Proc Natl Acad Sci USA 38(10):3407-3411
8 Csermely, P., Schnaider, T., Soti, C. et al. (1998) The 90 kDa Molecular Chaperone Family: Structure, Function and Clinical Applications A Comprehensive Review. Pharmacol Ther 79(2):129-168
9 Sapozhnikov, A. M., Ponomarev, E. D., Tarasenko, T. N. et al. (1999) Spontaneous apoptosis and expression of cell-surface het-shock proteins in cultured EL-4 lymphoma cells. Cell Proliferation 32(6):363-378
10 Gabor, A., Nora, M., Tamas, V., et al. (2015) ITOC2 – 018. Hyperthermia induced immunogenic cell-death. Eur J Cancer. 51(1): S7
11 Hupp, T. R., Meek, D. W., Midgley, C. A. et al. (1992) Regulation of the Specific DNA Binding Function of p53. Cell 71(5): 875-886
12 Dani, A., Varkonyi, A., Magyar, T., and Szasz, A. (2010) A retrospective study of 1180 cancer patients treated by oncothermia. Forum Hyperthermia accepted (pp. 1–11)
13 Mole, R. H. (1953) Whole body irradiation-radiology or medicine? Br J Radio 26: 234- 241
14 Seong, M. Y. and Jung S. L. (2011) Case of Abscopal effect with Metastatic Non-Small-Cell Lung Cancer, submitted to BMJ
15 Wiedermann, G. J., Feyerabend, T., Mentzel, M. et al. (1994) Thermochemotherapie: grunde fur die kombinationsbehandlung mit hyperthermia und chemotherapie. Focus Mul 11:44-50
16 Issels, R.D., Abdel-Rahman, S., Salat, C. et al (1998) Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) followed by surgery and radiation in primary recurrent high-risk soft tissue sarcomas (HR STS) of adults (updated report), J. Cancer Res. Clin. Oncol. 124:R105
17 LeVeen, H. H., Rajagopalan, P. R., Vujic, I. et al. (1984) Radiofrequency thermotherapy, local chemotherapy, and arterial Occlusion in the treatment of non-resectable cancer. Am Surg 50(2):61-65
18 Okamura, K., Nakashima, K., Fukushima, Y. et al. Hyperthermia with low dose chemotherapy for advanced non-small-cell lung cancer. http://www.isshin.or.jp/okamura/awaji2004/awaji1.html
19 Streffer, C. (1995) Molecular and cellular mechanism of hyperthermia In: Seegenschmiedt MH., Fessenden P., Vernon CC. (Eds.) Thermo-radiotherapy and Thermo-chemotherapy, Vol. 1. Biology, physiology and physics, Springer Verlag, Berlin Heidelberg, pp. 47-74
20 Okumura, Y., Ihara, M., Shimasaki, T. et al. (2001) Heat inactivation of DNA-dependent protein kinase: possible mechanism of hyperthermic radio- sensitization, in: Thermotherapy for Neoplasia, Inflammation, and Pain, (Kosaka M, Sugahara T, Schmidt KL, Simon E (Eds.)), Springer Verlag Tokyo pp. 420-423
21 Masunaga, S., Hiraoka, M., Akuta, K. et al. (1990) Non-Randomized Trials of Thermoradiotherapy versus Radiotherapy for Preoperative Treatment of Invasive Urinary Bladder Cancer. J Jpn Soc Ther Radiol Oncol 2: 313-320
22 Pearson AS, Izzo F, Fleming RYD et al (1999) Intraoperative radiofrequency ablation of cryoablation for hepatic malignances. Amer J Surg 178(6):592-598
23 Kouloulias, V. E., Kouvaris, J. R., Nikita, K. S. et al. (2002) Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre- intra- and post operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma. Int.J Hyperthermia 18:233-252
24 Kodama, K., Doi, O., Higashyama, M. et al. (1993) Long-term results of postoperative intrathoracic chemo-thermotherapy for lung cancer with pleural dissemination. Cancer 72(2):426-431
25 Ohtsuru, A., Braiden, V., and Cao, Y. (2001) Cancer Gene Therapy in Conjunction with Hyperthermia Under the Control of Heat-Inducible Promoter. In: Kosaka M, Sugahara T, Schmidt KL (eds) Thermotherapy for Neoplasia, Inflammation, and Pain, Springer Verlag .Tokyo, pp 464-470
26 Gaber, M. H., Wu, N. Z., Hong, K. et al. (1996) Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. Int J Radiat Oncol Biol Phys 36(5):1177-1187
27 Yerushalmi, A., Shani, A., Fishelovitz, Y. et al. (1986) Local microwave hyperthermia in the treatment of carcinoma of the prostate. Oncology 43(5):299-305
28 Oleson, J. R., Calderwood, S. K., Coughlin, C. T., et al. (1988), Biological and Clinical Aspects of Hyperthermia in Cancer Therapy. Am. J. Clin. Oncology 11:368-380
29 Henderson, B. W., Waldow, S. M., Potter, W. R., et al. (1985) Interaction of Photodynamic Therapy and Hyperthermia: Tumor Response and Cell Survival Studies after Treatment of Mice in Vivo. Cancer Research 45:6071-6077
30 Lohr, F., Hu, K., Huang, Q., et al. (2000) Enhancement of radiotherapy by hyperthermia-regulated gene therapy. International Journal of Radiation Oncology Biology Physics 48:1513-1518
31 Skitzki, J. J., Repasky, E. A., and Evans, S. S. (2009) Hyperthermia as an immunotherapy strategy for cancer. Current Opinion in Investigational Drugs 10:550-558
32 Vertrees, R. A., Jordan, J. M., and Zwischenberger, J. B. (2007) Hyperthermia and Chemotherapy: The Science. In: Current Clinical Oncology, Intraperitoneal Cancer Therapy, Hlem CW. Edwards RP. (Eds.) Humana Press, Totowa NJ, USA
33 Kovago, C. S., Meggyeshazi, N., Andocs, G. et al. (2013) Report of the pilot-study done for the proposed investigation on the possible synergic effect between high dose ascorbic acid application and oncothermia treatment. Oncothermia Journal 7:283-284
34 Gonzalez-Gonzalez, D. Thermo-radiotherapy for tumors of the lower gastro- instenstinal tract. In: M.H. Seegenschmiedt, M.H., Fessenden, P., Vernon, C.C. (eds.) Thermo-radiotherapy and Thermo-chemotherapy. Biology, physiology and physics, Vol. 1, pp. 105-119, Springer Verlag, Berlin, Heidelberg (1996)
35 Bruera, E. (2006) Process and content of Decision making by advanced cancer patients. J Clin Oncol 24:1029-1030
36 Tassinari, D., Montanari, L., Maltoni., M. et al. (2008) The palliative prognostic score and survival in patients with advanced solid tumors receiving chemotherapy. Supportive Care of Cancer 16:359-370
37 Burd, R., Dziedzic ,T. S., Xu, Y. et al. (1998) Tumor Cell Apoptosis, Lymphocyte Recruitment and Tumor Vascular Changes Are Induced by Low Temperature, Long Duration (Fever-Like) Whole Body Hyperthermia. J Cellular physiology, 177:137-147
38 Vujaskovic, Z. (2013) Clinical trials in breast and bladder cancer: Thermally enhanced chemosensitization and drug delivery. Oncothermia J 7:69-69
39 Gramaglia, A., Parmar, G., Ballerini, M., et al. (2013) Liposomiated doxarubycyn (LD) and hyperthermia on glioblastoma relapsing after surgery, radiotherapy and two chemotherapy lines: a case report. Oncothermia J 7:359-359
40 Hager, E. D., Dziambor, H., App, E. M., et al. (2003) The treatment of patients with high-grade malignant gliomas with RF-hyperthermia. Proc ASCO 22:118
41 Sahinbas H., Baier J. E., Groenemeyer, D. H. W., et al. (2006) Retrospective clinical study for advanced brain-gliomas by adjuvant oncothermia (electro-hyperthermia) treatment. www.gimt-online.de /uploads/media Therapieergebnisse_Giloma_Studie_01.pdf
42 Sahinbas H., Groenemeyer, D. H. W., Boecher, E., et al. (2006) Retrospective clinical study of adjuvant electro-hyperthermia treatment for advanced brain-gliomas. Deutche Zeitschrifts fuer Onkologie 39:154-160
43 Szasz, A., Sahinbas, H., Dani, A. (2004) Electro- hyperthermia for anaplastic astrocytoma and glioblastoma multiforme. ICACT, Paris 9-12 February 2004
44 Sahinbas, H. (2004) EHT bei Kindern mit Hirntumoren und nicht-invasive Messverfahren am beispiel von Hirntumoren. Symposium Hyperthermie, Cologne, 15-16
45 Sahinbas, H. and Grönemeyer, D. (2005) Oncothermia: An effective treatment for advanced gliomas. Deutsche Kongress im Komplementare Medizine, June 2005, Schortens
45 Sahinbas, H. (2004) Deep RF hyperthermia treatment of advanced gliomas. Oncology Conference, Basel
46 Sahinbas, H. et al. (2004) Hyperthermia treatment of advanced relapsed gliomas and astrocytoma. The 9th International Congress on hyperthermic oncology, ICHO, St. Louis, Missuri, 24-27 April 2004
47 Hager, E. D. et al. (2003) The treatment of patients with high-grade malignant gliomas with RF-hyperthermia. Proc ASCO 22:118
48 Hager, E. D. et al. (2008) Prospective phase II trial for recurrent high-grade malignant gliomas with capacitive coupled low radiofrequency (LRF) deep hyperthermia. ASCO, Journal of Clinical Oncology, Annual Meeting Proceedings (Post-Meeting Edition) 26:2047
49 Hager, E. D. (2004) Response and survival of patients with gliomas grade III/IV treated with RF capacitive-coupled hyperthermia. ICHO Congress, St. Louis, US
50 Hager, E. D. (2004) Clinical Response and Overall Survival of Patients with Recurrent Gliomas Grade III/IV Treated with RF Deep Hyperthermia – An Update. ICHS Conference, Shenzhen, China
51 Fiorentini, G., Giovanis, P., Rossi, S., et al. (2006) A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia. In Vivo 20:721-724.
52 Jückstock, J., Eberhardt, B., Kirchner, H., et al. (2013) Locoregional hyperthermia combined with chemotherapy for metastatic breast cancer patients – preliminary results of the Mammatherm-trial. Oncothermia J 7:368-368
53 Kikumori, T., Kobayashi, T., Sawaki, M., et al. (2009) Anti-cancer effect of hyperthermia on breast cancer by magnetite nanoparticle-loaded anti-HER2 immunoliposomes. Breast Cancer Res Treat 113:435–441
54 Vujaskovic, Z. (2013) Clinical trials in breast and bladder cancer: Thermally enhanced chemosensitization and drug delivery. Oncothermia J 7:69-69
55 Coletta, D., Gargano, L., Assogna, M., et al. (2013) Stabilization of metastatic breast cancer with capacitive hyperthermia plus standard-dose chemotherapy and/or metronomic. Oncothermia J 7:302-304
56 Pesti, L., Dankovics, Z. S., Lorencz, P., et al. (2013) Treatment of advanced cervical cancer with complex chemoradio – hyperthermia. Oncothermia J 7:289-291
57 Strauss, C. A., Kotzen, J. A., Baeyens, A., et al. (2013) Oncothermia in HIV positive and negative locally advanced cervical cancer patients in South Africa. Oncothermia J 7:306-308
58 Fiorentini, G., De Simone, M., Turriti, G. et al. (2005) Deep electro-hyperthermia with radiofrequencies combined with thermoactive drugs in patients with liver metastases from colorectal cancer (CRC): a Phase II clinical study. 22th Annual Meeting of the European Society for Hyperthermic Oncology, Graz, Austria, 8-11 June 2005
59 Morita, M., Kuwano, H., Araki, K. et al. (2001) Prognostic significance of lymphocyte infiltration following preoperative chemoradiotherapy and hyperthermia for esophageal cancer. International Journal of Radiation Oncology 49(5):1259–1266.
60 Donato, V., Zurlo, A., Banelli E. et al. (1996) Local hyperthermia and radiation therapy in the treatment of superficially located lymphomas and recurrent Hodgkin’s disease. Oncol Rep. 3(6):1043-7.
61 Hager, E. D., Krautgartner, I., Popa, C. (1999) Deep Hyperthermia with short waves of patients with advanced stage lung cancer. Hyperthermia in clinical practice. XXII Meeting of the International Clinical Hyperthermia Society
62 Dani, A. (2003) Clinical experience of electro-hyperthermia for advanced lung tumors. ESHO Conference, Munich
63 Dani, A. et al. (2004) Treatment of non-small-cell lung cancer by electro-hyperthermia. Strahlenbiologie und Medizinische Physik Deutscher Kongress für Radioonkologie, DEGRO, Erfurt 10-13 June 2004
64 Lee, D. Y., Haam, S. J., Kim, T. H., et al. (2013) Oncothermia with chemotherapy in the patients with small cell lung cancer. Oncothermia J 7:349-356
65 Seong, G. M. (2013) A case of clinically complete remission of lung with hyperthermia and concurrent 5th-line chemotherapy in a disseminated NSCLC patient. Oncothermia J 7:389-389
66 Douwes, F. R. (2013) Local and whole body hyperthermia in chemoresistant ovarian cancer. Oncothermia J 7:70-70
67 Dani, A., Varkonyi, A., Magyar, T., et al. (2008) Clinical study for advanced pancreas cancer treated by oncothermia. Forum Hyperthermie 1:13-20
68 Assogna, M., Castigliani, G., Coletta, D., et al. (2013) Chemotherapy combined with regional hyperthermia in locally advanced unresectable pancreatic cancer: clinical and anthropological benefits. Oncothermia J 7:116-118
69 Bogovic, J., Douwes, F., Muravjov, et al. (2001) Posttreatment histology and microcirculation status of osteogenic sarcoma after a neoadjuvant chemo- and radiotherapy in combination with local electromagnetic hyperthermia. Onkologie 24:55-58
70 Brunner, G. and Erkell, L. (2008) Cellular and molecular effects of electrohyperthermia in a cell model of skin cancer progression. 10th International Congress on Hyperthermic Oncology, Munich, Germany, 9-12 April 2008
71 Jeung, T. S., Ma, S. Y., Yu, J., et al. (2013) Cases that respond to oncothermia monotherapy. Conference Paper. Hindawi Publishing Corporation Conference Papers in Medicine. Volume 2013, Article ID 392480, 12 pages