What is Hyperthermia for Cancer Treatment?

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Hyperthermia as a cancer treatment (also called thermal therapy) refers to the use of high temperatures to treat the disease. It may be used alone or in combination with chemotherapy, immunotherapy, radiation therapy, or other treatments, and may be delivered locally, regionally, or to the whole body, depending on the type and stage of cancer being treated.

Despite significant evidence showing its efficacy, its availability is often limited to larger cancer centers and is most commonly used in the setting of a clinical trial.

Nanotechnology hyperthermia for cancer illustration

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History

Hyperthermia not a new treatment for cancer. Treating cancer with the use of heat (cauterization) is recorded back as far as 5000 BC, and Hippocrates claimed the ability to treat cancers with heat was what distinguished curable from incurable cancers.

A century ago, physicians were familiar with a phenomenon in which cancers regressed or sometimes went away completely. This improvement and sometimes complete disappearance of a tumor was often seen following an infection accompanied by a high fever (often erysipelas) or following injections of killed cultures of streptococci or a type of bacillus. Following the introduction of antibiotics, however, this spontaneous remission of cancer was seen only infrequently.

Uses

Hyperthermia—either local, regional, or whole-body—can be administered alone or in combination with chemotherapy, radiation, or immunotherapy for a number of different cancers. Some of these include:

  • Breast cancer (especially with locally advanced and recurrent disease)
  • Head and neck cancer
  • Lung cancer (non-small cell lung cancer)
  • Melanoma
  • Sarcomas
  • Cervical cancer
  • Prostate cancer
  • Uterine cancer
  • Colon cancer
  • Ovarian cancer (metastatic) and primary peritoneal cancer
  • Appendix cancer
  • Lymphomas
  • Squamous and basal cell skin cancers

Types

Hyperthermia may be used alone or in combination with other treatments. Methods are frequently broken down into those that are:

  • Local, for tumors near the surface of the body or that can be reached through probes
  • Regional
  • Whole body (usually for metastatic tumors)

How It Works

The mechanism behind hyperthermia for cancer depends on the method of treatment. These include:

  • High temperatures: Used to kill cancer cells.
  • Mild temperatures: Used to sensitize cancer cells to other treatments or enhance the ability of these treatments to reach cancer cells.

In addition to direct damage, hyperthermia can cause damage at the molecular level such as:

  • Disrupting DNA repair in cancer cells
  • Releasing certain chemicals
  • Activating an immune response to a cancer

Ablation of Cancer Cells

With local therapies such as radiofrequency ablation, high temperatures are used to directly damage cancer cells and surrounding tissues.

Cancer cells—as well as the blood vessels that supply malignant tumors—differ from those of normal cells. These differences, in turn, can result in different responses to heat. In addition, heating can inhibit the process of tumor growth (cell division) as well as the ability of cancer cells to spread (metastasize).

Enhancement of Treatments

Hyperthermia may enhance the cell-killing effect of treatments such as:

These benefits have been seen with a number of different cancers, such as sarcomas and those of the esophagus, digestive tract, pancreas, breast, cervix, bladder, head and neck, and more.

With all of these treatments, hyperthermia may increase blood flow (and hence oxygen delivery) to a tumor so that it is more susceptible to the cell-killing effects, but there are other effects that can be specific to the treatment type.

When hyperthermia is used with chemotherapy or radiation therapy, it is usually used within one hour of treatment. An exception is with regional hyperthermia in which they are used at the same time.

After treatment with hyperthermia, there is a period of transient insensitivity to the effects of hyperthermia. For this reason, hyperthermia is used once or twice weekly with radiation at the most.

Chemotherapy

Hyperthermia can enhance the effect of chemotherapy, and this may be:

  • Additive
  • Synergistic (work better than would be expected by the combination of hyperthermia and chemotherapy alone)
  • Act in ways that are independent of the interaction.

An increase in temperature surrounding a tumor can alter the lipids in cancer cells so that chemotherapy drugs can gain access more easily. With some drugs—such as cisplatin—this results in a synergistic effect. With others—such as carboplatin and oxaliplatin—the effect is additive.

Radiation Therapy

Hyperthermia increases the sensitivity of cancer cells to ionizing radiation in a few ways. These include:

  • Increased sensitivity to radiation: This occurs because of the increased blood flow (from mildly elevated temperatures but not high temperatures).
  • Reduced ability of cancer cells to repair damage: This is caused by changes in DNA repair proteins due to heat.
  • Induced production of heat shock proteins: These proteins (in a mechanism that interferes with the activity of an enzyme called telomerase) promote the death of the cells.

The effects of hyperthermia combined with radiation vary depending on cancer type and stage, but overall, it appears to improve the effectiveness of radiation by roughly 50%.

The use of hyperthermia is particularly exciting in the setting of recurrent cancers. Radiation therapy is often limited due to relative hypoxia in tissues, and this has been a significant problem with recurrent tumors. It's now thought that via elimination of this relative hypoxia, the combination of hyperthermia and radiation may allow for the treatment of cancers that have been previously treated with radiation but have recurred.

Immunotherapy

Since the generally low oxygen level (hypoxia) surrounding a tumor (the microenvironment) appears to play a role in the relative immunosuppressive state of the tissue microenvironment, it's thought that hyperthermia could—through increased blood flow—improve the effectiveness of immunotherapy drugs such as checkpoint inhibitors.

While studies looking at the effectiveness of combining hyperthermia with immunotherapy have not yet been done, preclinical studies suggest that the combination could enhance the effect of immunotherapy at all eight steps in the cancer-immunotherapy cycle.

It's thought that adding hyperthermia to immunotherapy may be particularly helpful in the treatment of metastatic melanoma and head and neck cancers.

The Abscopal Effect

Researchers hope that combining hyperthermia with radiation therapy and immunotherapy may enhance a phenomenon known as the abscopal effect; but the true effect, if any, remains to be seen.

Inhibiting the Repair of Damaged Cancer Cells

Cells, including cancer cells, produce proteins that work to repair damaged DNA. When cancer cells are unable to repair the damage caused by treatment, they are more likely to die.

Hyperthermia is thought to disable DNA repair enzymes within cells, thus interfering with this repair.

Enhancing the Immune System and Reducing Immune Suppression

In addition to enhancing cancer treatments (and reducing the ability of repair), hyperthermia is thought to

  • Enhance the body's immune response to cancer cells
  • Reduce the immune suppression
  • Reduce the immune escape of cancer

When combined with radiation, activation of immune response appears to involve both the innate immune system and adaptive immune system, affecting cells ranging from T cells, to natural killer cells, to macrophages, and more.

Local Hyperthermia

Local hyperthermia involves the use of high heat which is applied to a small (local) area of tissue to kill cancer cells and the blood vessels that supply a tumor. In this case, instead of removing a tumor, the cancer cells are heated and disintegrate. While it varies, temperatures of 103 to 110 degrees Fahrenheit are most often applied for a period of 45 to 90 minutes.

In many cases, local hyperthermia is used:

  • As an alternative to surgery
  • For those who have tumors that are difficult or impossible to access via surgery
  • For people who would not tolerate surgery

The technique may be used for an initial tumor, or for recurrent/metastatic tumors. The use is usually restricted to tumors that are 5 centimeters (around 2 1/2 inches) in diameter or less.

Unlike surgery that removes a tumor, local hyperthermia leaves behind scar tissue. On conventional scans such as CT or MRI, this can sometimes be difficult to distinguish from an actively growing tumor. Fortunately, positron emission tomography (PET scan) is a functional test that can often make this distinction.

The heat may take the form of:

  • Radiofrequency ablation (high energy radio waves): the most common method
  • Microwaves
  • Ultrasound (high intensity focused ultrasound)
  • Others

Local hyperthermia may be used in different ways:

  • Externally: To treat tumors near the skin surface (less than 3 to 4 inches below the surface).
  • Intraluminally: To treat deeper regions of the body that are accessible through special techniques, such as the esophagus during an endoscopy.
  • Interstitially: To treat tumors that are deeper in the body but can be reached by a probe to introduce a heat source. For example, radiofrequency ablation may be used via a needle inserted into the tumor to treat cancers of the brain, lung, liver, or kidney. The probe is usually kept in place for around 30 minutes.

Methods of treatment vary, but with surface hyperthermia, a surface applicator is usually applied directly over the tumor.

Regional Hyperthermia

In contrast to local hyperthermia, regional hyperthermia involves the treatment of a larger area, for example, part of all of an organ or a limb such as an arm or leg.

Regional hyperthermia may be used:

  • Externally: Treating a deeper area than local hyperthermia.
  • Regionally (isolation perfusion): In this technique, blood from an area such as the leg may be removed, heated, and reintroduced along with chemotherapy to treat cancers such as sarcomas and melanomas.
  • Deep tissue: An example of deep tissue regional hyperthermia may be used in the treatment bladder cancer. The device is placed over the bladder, and microwave or radiofrequency waves used to heat the region.

Whole Body Hyperthermia

Whole body hyperthermia is used primarily for metastatic cancers.

The goal is to heat the entire body in order to raise body temperature to 107 to 108 degrees Fahrenheit for a period of 90 minutes or more. This may be done with the use of:

  • Hot water blankets
  • Thermal chambers that resemble incubators used for babies
  • Immersing a person in warm water

Hyperthermia in Combination Therapy

There are many combinations of hyperthermia, chemotherapy, and radiation that have been used or are currently being studied in clinical trials. We will not cover all of these but will provide a few examples to illustrate how these combinations may be used.

Chemotherapy

Hyperthermia along with neoadjuvant chemotherapy (chemotherapy before surgery) has been used to treat people who have high-risk soft-tissue sarcomas and has been compared with the use of chemotherapy alone.

In a 2018 study, the combination of hyperthermia and chemotherapy resulted in improved survival as well as progression-free survival for people with soft tissue sarcomas compared with those who received chemotherapy alone.

Radiation

When cancer spreads to bones (bone metastases) people often experience severe pain.

Researchers compared the use of radiation therapy alone to treat bone metastases with that of radiation therapy plus hyperthermia (hyperthermia applied within an hour of the radiation). It was found that those who received the combination therapy had almost twice the response to treatment (reduction in pain) as those who received radiation therapy alone.

Hyperthermia in combination with radiation may be particularly helpful in some settings. A 2019 review of studies looking at the use of hyperthermia combined with radiation therapy for recurrent breast cancer found that the combination appeared to influence the complete response, the duration of responses, and overall survival compared with the use of radiation therapy alone. Similar benefits have been noted in studies looking at melanoma, sarcoma, and cervical cancer.

Combination with Supportive Care in Refractory Cancer

A 2020 study showed promise for the use of hyperthermia for those with the most advanced tumors.

A combination of hyperthermia (modulated electrohyperthermia three times weekly for 25 sessions) plus intravenous vitamin C was given to a group of people with advanced, refractory non-small cell lung cancer. Though the study was small, it did show a controlled rate of 42.9% in the treatment group compared with 16.7% in a group that received the best supportive care alone.

Quality of life was also better in the treatment group. While the study primarily demonstrated safety in using hyperthermia in this setting, and did raise the hope for further studies looking for methods to improve quality of life for those with advanced cancers.

Risks and Side Effects

The risks and side effects of hyperthermia tend to be relatively mild, especially compared with the side effects of many other cancer treatments. Certainly, the risks will vary depending on the:

  • Specific type of hyperthermia
  • Duration of use
  • Specific delivery system used

Adverse effects of local hyperthermia can include burns and the resultant pain associated with burns. With regional hyperthermia, there have been some reports of serious muscle necrosis (death of muscle) and subcutaneous fat which required surgery, but this is uncommon.

The risks of whole-body hyperthermia are similar to those to be expected with a significantly elevated body temperature and may include

  • Feeling hot
  • Fatigue
  • Foss of the ability to sweat due to rapid temperature elevation

More serious conditions may include:

  • Dehydration
  • Heat exhaustion
  • Heatstroke

Severe symptoms may be more common in people with certain underlying health conditions. Since high temperatures can be damaging to the peripheral nervous system, it should not be used in people who have neurodegenerative conditions such as multiple sclerosis.

Can Hyperthermia Cause Cancer Growth?

Fortunately, there do not appear to be any reports in which hyperthermia has resulted in the growth or progression of cancer.

Both regional and whole-body hyperthermia may also result in:

  • Nausea
  • Vomiting
  • Diarrhea

More involved techniques—such as regional hyperthermia in which the blood is removed from a limb and warmed—clearly carries risks related to perfusions such as blood clots and more.

Limitations

Some limitations of hyperthermia include:

  • Challenges accurately measuring and maintaining the ideal temperature within a tumor.
  • Limited availability, since the full range of hyperthermia options is offered at relatively few cancer centers across the country.
  • Strict eligibility criteria for clinical trials.
  • Varied scenarios for insurance coverage.

A Word From Verywell

Hyperthermia for treating cancer is spoken of less frequently than many other treatments, but that is not due to a lack of effectiveness. The improved response to radiation therapy—in particular—is worth noting, but many people with cancer are unaware of this treatment option if it is not offered at their cancer center.

What this emphasizes is the importance of being your own advocate in your cancer care and asking about all options that may be available even if they are not offered at your cancer center. Fortunately, many National Cancer Institute-designated cancer centers are now offering remote (virtual) consults so that people can get second opinions and learn before traveling for treatment might be a good option.

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  1. Datta NR, Kok HP, Crezee H, Gaipl US, Bodis S. Integrating loco-regional hyperthermia into the current oncology practice: swot and tows analysesFront Oncol. 2020;10:819. doi:10.3389/fonc.2020.00819

  2. Fiorentini G, Sarti D, Gadaleta CD, et al. A narrative review of regional hyperthermia: updates from 2010 to 2019Integr Cancer Ther. 2020;19:153473542093264. doi:10.1177/1534735420932648

  3. Cheng Y, Weng S, Yu L, Zhu N, Yang M, Yuan Y. The role of hyperthermia in the multidisciplinary treatment of malignant tumorsIntegr Cancer Ther. 2019;18:153473541987634. doi:10.1177/1534735419876345

  4. Peeken JC, Vaupel P, Combs SE. Integrating hyperthermia into modern radiation oncology: what evidence is necessary? Front Oncol. 2017;7:132. doi:10.3389/fonc.2017.00132

  5. Elming P, Sørensen B, Oei A, et al. Hyperthermia: the optimal treatment to overcome radiation resistant hypoxiaCancers. 2019;11(1):60. doi:10.3390/cancers11010060

  6. Hurwitz MD. Hyperthermia and immunotherapy: clinical opportunities. Int J Hyperthermia. 2019;36(sup1):4-9. doi:10.1080/02656736.2019.1653499

  7. Lee S, Son B, Park G, et al. Immunogenic effect of hyperthermia on enhancing radiotherapeutic efficacy. IJMS. 2018;19(9):2795. doi:10.3390/ijms19092795

  8. American Cancer Society. Hyperthermia to treat cancer. Updated May 3, 2016.

  9. Issels RD, Lindner LH, Verweij J, et al. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the eortc 62961-esho 95 randomized clinical trialJAMA Oncol. 2018;4(4):483. doi:10.1001/jamaoncol.2017.4996

  10. Chi MS, Y KL, Chang YC, et al. Comparing the effectiveness of combined external beam radiation and hyperthermia versus external beam radiation alone in treating patients with painful bony metastases: A phase 3 prospective, randomized, controlled trial. Int J Radiat Oncol Biol Phys. 2018;100(1):78-87. doi:10.1016/j.ijrobp.2017.09.030

  11. Bakker A, van der Zee J, van Tienhoven G, et al. Temperature and thermal dose during radiotherapy and hyperthermia for recurrent breast cancer are related to clinical outcome and thermal toxicity: a systematic review. Int J Hyperthermia. 2019;36(1):1024-1039. doi:10.1080/02656736.2019.1665718

  12. Ou J, Zhu X, Chen P, et al. A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer. J Adv Res. 2020;24:175182. doi:10.1016/j.jare.2020.03.004

  13. Yagawa Y, Tanigawa K, Kobayashi Y, Yamamoto M. Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery. Journal of Cancer Metastasis and Treatment. 2017.

Additional Reading
  • Kok HP, Cressman ENK, Ceelen W, et al. Heating technology for malignant tumors: a review. Int J Hyperthermia. 2020;37(1):711-741. doi:10.1080/02656736.2020.1779357

  • Tepper JE, Foote RL, Michalski JM, eds. Gunderson & Tepper's Clinical Radiation Oncology. 5th ed. Philadelphia, PA: Elsevier; 2021