Turning up the heat helps shrink tumors

THE BALTIMORE SUN

A year ago, when Gayle Driscoll's cancer recurred on her skin, the 63-year-old retired teacher from Barnstable, Mass., tried an experimental treatment that gave her radiation therapy some extra oomph.

Every time she lay down for radiation treatment on her chest, her tumors were also heated with a device that emitted radio frequency waves. After six weeks, the skin tumors were gone.

The heat therapy called hyperthermia was meant only as a local treatment - and the cancer ultimately spread to her bones - but it was "psychologically important" to her to see the tumors in her skin disappear, she said.

Hyperthermia, in which microwaves are used to raise the temperature of a tumor - or the patient's whole body - to 104 to 106 degrees Fahrenheit, is a new twist on an old treatment idea that has gained new currency recently, thanks to some successful studies.

Hyperthermia significantly boosts the killing power of chemotherapy and radiation. It is generally used to help prevent local recurrences, but some doctors speculate that it may improve overall survival as well.

At least eight studies in recent years have shown that adding hyperthermia to chemotherapy or radiation can improve local control of cancers of the esophagus, cervix, head and neck, brain, melanoma and breast cancers that have spread to the chest wall, said Dr. Mark Dewhirst, director of the hyperthermia program at Duke University Medical Center in Durham, N.C.

Scientists who have observed first hand the effects of hyperthermia are impressed. "I'm amazed at some of the tumors that just melt away with the combination of radiation and heat," said Dr. David Wazer, radiation oncologist-in-chief at the Tufts-New England Medical Center.

'Rapid regression'

At Long Beach Memorial Medical Center in California, Dr. Nisar Syed, director of radiation oncology, has treated more than 3,000 patients with hyperthermia plus radiation over the years. In many cases, "We saw rapid regression of the tumor," he said, "and in some cases, improved survival as well."

Hyperthermia could turn out to be among the most powerful anti-cancer weapons. Consider this idea, now being studied at Duke:

Researchers have created a tiny bubble, or liposome, with water on the inside and a ring of fat on the outside. Mixed in with the water is the chemotherapy drug doxorubicin. The liposome is designed to be stable at body temperature but to burst when heated.

By using hyperthermia to explode the liposomes, Dewhirst has shown in mice that doctors can deliver 30 times more chemotherapy than would otherwise be possible.

Scientists think hyperthermia fights cancer in several ways.

"When you combine heat and radiation, the cell-killing of cancer cells is better," said Dr. Jay Harris, chairman of radiation oncology at Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston.

Radiation works by damaging DNA. But there must be enough oxygen nearby for this damage to occur. Parts of tumors are tough to kill because they have a poor blood supply and, thus, low oxygen levels. Raising the temperature of a tumor brings more blood, hence more oxygen, to the tumor.

With chemotherapy, drugs get in through small channels on the cell surface. "The heat opens these channels so that chemotherapy drugs can more easily enter in," said Wazer of the Tufts-New England Medical Center.

Hyperthermia also seems to "jump-start the immune response," at least in mice, said Elizabeth Repasky, an immunology professor at the Roswell Park Cancer Institute in Buffalo, N.Y., who is looking at the effects in humans. Just as a fever with the flu may boost immune response, so may hyperthermia, a kind of artificial fever.

The idea of using heat to treat cancer started more than 100 years ago when an American surgeon, Dr. William B. Coley, noticed that some cancer patients who also had high fevers from bacterial infections had their tumors shrink. He began inducing fevers on purpose in cancer patients by infecting them with bacteria.

Several decades ago, a number of medical centers, including Dana-Farber and Johns Hopkins Medical Institutions, began pursuing the idea - with disappointing results. Insurance payments for the procedures were low and a major study about 15 years ago showed no benefit to hyperthermia, though the study was flawed.

"So the technique was by and large abandoned," said Wazer.

At Hopkins, Dr. Ding-Jen Lee, a radiation oncologist, ran the hyperthermia program for 10 years until he retired last summer. Though the program is over, Lee said he remains "very convinced" of the benefits, especially for melanoma and breast cancer.

Research continues

The good news is that today, reimbursement rates are increasing and the instruments that can deliver microwaves even to tumors deep in the body are more precise. In the past few years, new, better-designed studies "have rekindled interest" in the idea, said Harris. Moreover, the National Cancer Institute recently opted to grant $19 million to Duke to continue its hyperthermia research.

Among the studies turning the tide for hyperthermia is one published last year by Dr. Ellen L. Jones, a Duke radiation oncologist. Writing in the Journal of Clinical Oncology, her team reported that, compared with patients getting radiation but not hyperthermia, those who got both had a significantly reduced risk of recurrence of "superficial" tumors, chiefly breast cancers that had spread to the chest wall.

"I really trust the data coming out of this Duke group," because the team was so meticulous, said Harris, who was not involved in the study.

In another study of 68 women with cervical cancer in the United States, Norway and the Netherlands, also published last year, Jones and colleagues showed that a triple combination --- hyperthermia, radiation and chemotherapy --- was highly effective at lowering the risk of recurrence. A larger study comparing this triple treatment with standard treatment is under way.

Dr. Joan M.C. Bull, director of thermal therapy research at the University of Texas Medical School at Houston, is pursuing whole-body hyperthermia for some kinds of cancers, including metastatic pancreatic cancer.

Bull places patients, head and all, inside a radiant heat machine that brings body temperature to that of a high fever, about 104 F. It's very safe, she said, though patients are monitored carefully. Some patients get "cranky" during the treatment, she said, as they might with a fever.

Working with rats, Bull has heated the body for about six hours, and found that chemotherapy can be given before, during and after heat treatment. Her early, still-unpublished results "appear promising," she said, particularly for cancers that have spread beyond a local area.

Clearly, more research is needed. But many regions have at least one center. In Boston, it's New England Medical Center; in Providence, a center is about to open at Rhode Island Hospital.

Send your questions to foreman@baltsun.com.

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