Heat Can Make Other Cancer Treatments More effective

chrisbFall 2013

Burning ice

ROBERT GRIFFIN, Ph.D., along with a few colleagues, has rediscovered the value in a cancer treatment — hyperthermia — begun many years ago but not yet widely used in the United States. Griffin is associate professor in the Department of Radiation Oncology in the UAMS College of Medicine and director of its Radiation Biology Division.

Using microwaves, ultrasound, lasers and radio frequency, therapeutic hyperthermia involves elevating the temperature in a part of the body so that it absorbs more heat than it dissipates.

In the late 1970s and into the 1980s, researchers thought that simply heating a tumor might kill it without the need for any other treatment like radiation or chemotherapy, but they lacked the ability to calibrate and measure delivery of that heat. Clinical trials of hyperthermia were  disappointing. Later it was discovered that a major reason was the temperatures were too low.

“The whole field turned upside down then,” Griffin said. “The clinical trials were not conclusive because of the lack of consistent thermal doses. That became a stigma, but since then the field of thermal medicine has been re-developing.”

Some of those early studies and quite a few large clinical studies since showed that hyperthermia was effective in conjunction with radiation therapy, but no one understood why. Eventually, it was the promise of combining those treatments that led researchers like Griffin to reexamine mechanisms by which hyperthermia acts on living tissue — specifically cancerous tissue.

Many tumors thrive in a hypoxic environment in which the oxygenation of the tumor is much lower than in normal tissue. Because tumors cannot dissipate heat as quickly as healthy tissue, they can get hotter than that tissue if enough heat is applied. Hyperthermia at relatively low levels — as in the early clinical use of thermal medicine — ends up increasing the amount of blood flow and oxygenation of the tumor, making it more sensitive to radiation and chemotherapies.

Burning iceOne of the challenges of cancer treatment is treating or killing all the cancer cells that are part of a tumor. Failing to do that can make the remaining cancer cells more resistant to radiation or chemotherapy should they start multiplying again. Increasing oxygenation means fewer cells survive initial treatments. Hyperthermia kills some of the cancer cells and makes the remaining ones more vulnerable when radiation or chemo therapies are applied.

Another rapidly growing aspect of the thermal medicine field is thermal ablation, or the destruction of tissue with high temperatures or even the converse — freezing.

“We’ve also found that combined with radiation therapy, thermal ablation can produce a good cure rate if done in the proper sequence,” Griffin said. “You would ablate first and irradiate second. You destroy a considerable portion of the tumor and what’s left becomes more oxygenated and more vulnerable to radiation in the days following the ablation.”

Technological advances in the last 15 years also have contributed to the effectiveness of hyperthermia as part of a combined treatment approach. MRI thermometry to measure the exact heat distribution and level in a tumor and surrounding tissue can allow physicians to deliver just the right temperature to the tumor.

“We now have many systems that heat at low temperatures, but we also have thermal ablation that destroys the tissue,” Griffin said. “That has become a large part of the field of interventional radiology.”