Giving radiation therapy in fewer but larger doses may be an alternative to standard radiation therapy for some women with early-stage breast cancer. A trial testing this approach, called hypofractionated radiation therapy, has found that the regimen tested did not increase long-term toxicities and resulted in rates of survival and local recurrence similar to those seen with standard radiation therapy. The study , published in the February 11, 2010, New England Journal of Medicine, had the longest follow-up results of any study to date of hypofractionated radiation therapy for breast cancer.
Breast-conserving surgery (BCS) plus adjuvant radiation therapy has been firmly established as a safe alternative to full mastectomy for most women with early-stage breast cancer. The radiation therapy part of that regimen is vital, as long-term data have shown that it greatly reduces the risk of tumor recurrence.
However, almost a third of women in North America do not get radiation therapy after BCS. “Although the use of breast-conserving surgery is increasing, the number of women who receive appropriate radiation therapy after breast-conserving surgery is actually decreasing,” said Timothy Whelan, M.D., professor of oncology at McMaster University in Ontario, Canada.
The reasons for this lack of adherence to treatment standards are numerous and complicated, but they include the fact that a standard course of radiation therapy requires 25 treatments spread out over 5 weeks, a significant added burden for many patients who have already undergone surgery and may be starting hormone therapy or chemotherapy. Because hypofractionated radiation therapy may be less burdensome than standard radiation therapy, some oncologists believe the finding could have an immediate impact on breast cancer care in the United States.
Renewing an Old Idea
“Back in the 1960s some treatment centers first tried hypofractionated radiation therapy, but the researchers didn’t decrease the total dose of radiation, so they saw an increase in toxicity,” said Dr. Whelan. “After that, there was a great reluctance to engage in hypofractionation.”
Starting in 1993, researchers coordinated by the Ontario Clinical Oncology Group randomly assigned 1,234 women with early-stage breast cancer that had not spread to nearby lymph nodes to receive either the international standard radiation dose—50 Gy of whole-breast radiation given in 25 fractions over 5 weeks—or a hypofractionated radiation schedule—42.5 Gy of whole-breast radiation given in 16 fractions over 3 weeks. Patients received hormone therapy, chemotherapy, or both as deemed necessary by their doctors.
Ten years after treatment, the incidence of local recurrence (recurrence in the same breast) was 7.5 percent in the standard radiation therapy group and 7.4 percent in the hypofractionated radiation group. The probability of survival at 10 years was also virtually identical: 84.4 percent in the standard radiation therapy group and 84.6 percent in the hypofractionated group.
Late toxic effects did increase over time, but with no significant differences observed between the groups. Ten years after treatment, 70.5 percent of women in the standard radiation therapy group had no skin problems associated with treatment, compared with 66.8 percent in the hypofractionated radiation group. Few cardiac-related deaths occurred in either group. And 71.3 percent of women in the standard radiation therapy group and 69.8 percent in the hypofractionated radiation group had excellent or good overall cosmetic outcomes, as measured by nurses associated with the trial.
“We made a tremendous effort to follow these women long term, because there were lots of concerns about increased toxicity with hypofractionation,” said Dr. Whelan. “We’ve fortunately been able to show that while there was some toxicity, it was equivalent to that seen with standard treatment.”
Careful Application Required
As radiation oncologists look to incorporate these results into their practice, Bhadrasain Vikram, M.D., chief of the Clinical Radiation Oncology Branch in NCI’s Division of Cancer Treatment and Diagnosis , cautioned that “it is important to understand that these results cannot be extrapolated beyond the women who were eligible for this study—that is, women who had negative surgical margins and did not need radiation to their axillary lymph nodes.”
The results also cannot be applied to partial-breast irradiation, he explained, which uses hypofractionation but still as an experimental technique being tested in clinical trials.
But for whole-breast radiation in women who fit the study criteria, “it’s very confirmatory data, showing this works,” said Julia White, M.D., chair of the Radiation Therapy Oncology Group ’s breast committee and professor of radiation oncology at the Medical College of Wisconsin. “I think this will influence practice in the United States, in certain patients, and I think the women who would benefit the most are those for whom [a standard course of radiation therapy] is the most burdensome. Those are the women traveling a long way to get radiation and who might choose mastectomy.”