Hyperthermia Combined with Radiotherapy Can Improve Pain Control and Survival in Patients with Cancer

Several recent studies have pointed to the benefits of combining hyperthermia with radiation for pain relief and tumor control in cancer patients. Hyperthermia’s biologic effects include increasing cancer cells’ radiosensitivity and reducing their capability to repair radiation-induced DNA damage, while also enhancing blood flow and immune response to tumors.

In one study, the addition of hyperthermia was associated with improved pain control and extended the duration of pain relief in patients with bony metastases. Almost a two-fold difference in the complete response rate was observed between patients treated with the combination of hyperthermia and radiotherapy (58.6%) and patients treated with radiotherapy alone (32.1%).

A second study found increased survival and local progression-free survival in patients with localized high-risk soft-tissue sarcoma treated with neoadjuvant chemotherapy plus hyperthermia, compared to patients treated with chemotherapy alone. The difference in 5- and 10-year survival between the two groups was approximately 10%.

Despite evidence of hyperthermia’s benefits, Cleveland Clinic Cancer Center is one of only a few large clinical centers in the country, and the only center in Ohio, to offer this treatment modality. In a conversation with Consult QD, radiation oncologist Jennifer Yu, MD, PhD, shares her clinical experience with hyperthermia for pain and disease control in cancer patients. Dr. Yu is founder and Director of the Center for Hyperthermia, President of the Society for Thermal Medicine, and a cancer researcher in the Lerner Research Institute’s Department of Cancer Biology.

Q: Could you provide some historical background on hyperthermia and its therapeutic uses?

Dr. Yu: Hyperthermia has been used since ancient times, since the time of Hippocrates. In the 1980s and 1990s it became more popular, especially mild-temperature hyperthermia in combination with radiation therapy, which is what we offer at Cleveland Clinic.

Q: How is hyperthermia delivered and how long is a typical hyperthermia session?

Dr. Yu: We deliver hyperthermia to superficial sites — these are tumors that are typically within 3 cm from the skin surface. We’re aiming for a temperature of 109-110 °F (42-43 °C) and we heat the area for one hour. The temperature is monitored in real time to make sure we are not underheating or overheating the patients.

Typically, hyperthermia is delivered twice a week, but the exact schedule depends on the radiation schedule, because hyperthermia is delivered immediately preceding radiation, within 20 to 30 minutes. Usually, radiation is given over a period of two to five weeks, so patients can expect hyperthermia treatment to be performed twice a week for each week of radiation.

Q: How safe and well-tolerated is this treatment?

Dr. Yu: There is a small risk of developing blisters, which typically heal on their own.

Q: How is hyperthermia used to relieve pain in patients with bony metastases?

Dr. Yu: Hyperthermia uses heat to improve the effectiveness of radiation therapy by helping to reduce the efficiency of DNA damage repair that radiation causes within cancer cells, so patients can do better as a result of having more tumor killed within the heated area that is receiving radiation. It is believed that improved tumor control relieves compression of pain nerves or causes less irritation of those nerves. We have treated some patients with bony metastases using hyperthermia and radiation, and they had excellent responses that permitted them to reduce opioid pain medications or discontinue them. But most of our patients have been coming in for other indications, such as breast cancer recurrences.

Q: In which types of cancer has hyperthermia proven beneficial?

Dr. Yu: Hyperthermia has been shown to improve survival in sarcomas and cervical and ovarian cancers, so it should certainly be considered for many different types of cancer. We have treated patients with breast cancer, melanoma, head and neck cancer, vulvar cancer, rectal cancer, skin cancer and bony metastases from prostate and breast cancers.

Q: Can hyperthermia in combination with radiation provide curative treatment in patients with metastases?

Dr. Yu: We have seen tumors respond completely, meaning that they go away completely in the area that we’re treating with radiation and hyperthermia. In patients with recurrent breast cancers, we’ve had complete responses and patients who have been free of disease for four or six years [after treatment], and we’re still monitoring how they’re doing. So, essentially, these patients are either cured or have a very long remission period.

Q: What are the advantages of combining hyperthermia with radiation therapy?

Dr. Yu: Hyperthermia improves pain control and the durability of pain control. If you think about the quality of life, patients want to be free of pain, and if we can extend that period in which they’re free of pain, then their quality of life is significantly improved. In terms of the effects [of hyperthermia] on response, it can double the response to radiotherapy. Also, there are minimal side effects associated with this treatment, so it makes a lot of sense to use the combined treatment.

In addition, the cost of hyperthermia treatment is significantly less than that of radiation therapy. I have not had insurance denials, so I think insurance companies recognize the advantages of hyperthermia.