Heat Enhances Cancer Radiation Therapy

Heating tumors before radiation treatment has been shown to shrink the tumors completely in more patients with recurrent cancer than radiation treatment alone, according to a study by Duke Comprehensive Cancer Center radiation oncologists.

In a sample of 109 cancer patients, the researchers found that the dual therapy shrank tumors completely in 66 percent of patients with cancers in the breast, chest wall, head and neck, and skin (melanoma). By contrast, radiation alone caused full tumor shrinkage in 42 percent of patients.

The majority of patients were women with breast cancer that had recurred in the chest wall following mastectomy. The researchers said their findings clearly demonstrate that hyperthermia plus radiation should be the new standard of care for these women.

“The dual therapy offers the best potential for long-term cancer control in women whose cancer has recurred in their chest wall but has not spread elsewhere in the body, said Ellen Jones, MD, Ph.D., principal investigator of the study and a radiation oncologist at Duke.

Results of the study are published in the May 1, 2005, issue of the Journal of Clinical Oncology. Collaborators included Duke faculty from the departments of surgery, medical oncology, engineering and other radiation oncologists.

Patients with recurrent cancer have a poor prognosis because the cancer is typically aggressive and because a full dose of radiation is too toxic a second time, said Jones. Thus, finding new ways to improve the effectiveness of radiation is critical to enhancing the patient’s quality of life and potentially extending survival, she said.

“Adding hyperthermia to standard radiation gives us a strategy to get more mileage out of a modest dose of radiation for previously treated patients, who cannot tolerate a full dose,” said Jones. “The results of our trial set a new standard for how we define and determine a thermal dose of hyperthermia.”

Hyperthermia was even more effective among patients who had received radiation to treat their initial tumor, the researchers found. Among these patients, 68 percent had complete tumor shrinkage following the dual therapy versus 23 percent of patients who were receiving radiation for the first time.

Overall, the dual therapy did not extend survival for the patients in the study, primarily because so many patients had metastases (spreading cancer) elsewhere in the body, said Jones. However, she noted, hyperthermia improved local tumor control in the site of recurrence.

While extending survival is the ultimate goal of any treatment, even partial tumor shrinkage can improve a patient’s quality of life by reducing pain and discomfort caused by tumors, said Jones.

Hyperthermia uses microwave energy to raise the tumor’s temperature. The heat triggers a series of complex physiological events that are critical to the tumor’s demise, said the researchers. A tumor’s blood vessels are leakier than normal blood vessels, and heat opens blood vessel walls to an even greater extent, enabling chemotherapy and radiation to penetrate more effectively and sensitizing cells to radiation.

Heat also increases oxygen levels within the tumor, and oxygen is critical to the proper functioning of radiation and chemotherapy inside a cell. Finally, heat amplifies the level of DNA damage that chemotherapy and radiation inflict upon the cell by inhibiting enzymes that normally repair such DNA damage, said Jones.

While hyperthermia has been tested in conjunction with radiation and chemotherapy in numerous studies worldwide, those studies have produced conflicting results, said the researchers. The current study used precise dosing, rigorous quality controls and full tumor exposure to ensure that the effects of hyperthermia were accurate and quantifiable, said Jones.

“Two large clinical trials conducted in the 1980s produced negative results regarding the benefits of hyperthermia, yet there were concerns that objective data in these trials was lacking,” said Jones. “As a result, hyperthermia is not being utilized to its full potential in patients who could greatly benefit.”

The current study provides clinicians with a “verifiable prescription” for hyperthermia with clear cut dosing and temperature guidelines, said Jones.

Tumors treated in the study were characterized as “superficial,” meaning they were no greater than 3 centimeters in thickness. Small-size tumors ensured that the heat therapy would penetrate the entire depth of the tumor – a concern of previous trials, said Jones.

The study was funded by the National Cancer Institute.

From Duke University Medical Center

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