Wielding heat as a weapon
A year ago, when Gayle Driscoll’s breast cancer recurred on her skin, the 63-year-old retired teacher tried an experimental treatment that gave her radiation therapy some extra oomph. Every time she lay down for treatment on her chest, her tumors were also heated with a special 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 see the tumors in her skin disappear, the Barnstable, Mass., woman said.
Hyperthermia, in which energy is 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. And it’s gaining new currency in light of some successful studies.
The procedure 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 and 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 firsthand 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, chief radiation oncologist at Tufts-New England Medical Center in Boston.
At Long Beach Memorial Medical Center, Dr. Nisar Syed, director of radiation oncology, has treated more than 3,000 patients with hyperthermia plus radiation. In many cases, “we saw rapid regression of the tumor,” he said, and in some cases, improved survival as well.
In the future, hyperthermia could turn out to be among the most powerful anti-cancer weapons. 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 a 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 probably 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 both Dana-Farber Cancer Institute and Brigham and Women’s Hospital, both 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 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 now 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 Institute, 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 highly flawed.
“So the technique was by and large abandoned,” Wazer said.
The good news is that today, reimbursement rates are rising, and the instruments that can deliver microwaves even to tumors deep into the body are more precise. In the last few years, new, better-designed studies “have rekindled interest” in the idea, Harris said. 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.
In another study of 68 women with cervical cancer in the U.S., 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 underway.
