SAN DIEGO-Post-surgical radiation therapy can be reduced by 2 weeks without compromising tumor control in the breast and nearby areas, Chinese researchers have discovered after comparing the two approaches in more than 800 patients.
Five-year results of the clinical trial confirmed that tumor recurrence rates following 15 daily fractions of radiation, delivered over 3 weeks, were equivalent to those following 25 fractions delivered over 5 weeks in terms of overall survival, disease-free progression, and locoregional recurrence.
Women treated at 3 weeks also had fewer side effects, researchers reported at the American Society for Radiation Oncology Annual Meeting (Abstract 5).
"This is the first large, well-conducted clinical trial to demonstrate conclusively that hypofractionated radiation therapy to nodal regions of breast cancer is safe and effective in a post-mastectomy setting. This option makes treatment more convenient for patients, reduces medical expenses, and allows providers to treat more patients with limited resources," said Shulian Wang, MD, one of the study's lead authors and a radiation oncologist at the Chinese Academy of Medical Sciences in Beijing.
"The accelerated approach also has practical value for patients. With fewer treatment sessions, patients spend less time away from work and family, enjoy lower transportation costs and, as our findings show, experience fewer side effects."
Methods, Results
The shorter treatment approach was tested in 820 patients with high-risk breast cancer, 810 of them eligible for analysis. Almost all of the women, 93.9 percent, had stage III breast cancer, and the remaining patients had stage II disease.
Each patient underwent mastectomy and chemotherapy with taxanes and anthracycline (86%), 8.9 percent taxanes-based, and 1.9 percent with anthracycline-based chemo. In addition, 16.8 percent underwent trastuzumab targeted therapy and/or hormonal therapy (76.5% of all patients; 94.5% of eligible patients).
The women were randomly assigned to receive either hypofractionated or standard external beam radiation therapy to the chest wall and supra-infraclavicular nodal region. Accelerated regimen consisted of 43.5 Gray (Gy) delivered in 15 fractions over 3 weeks, while others received a standard regimen of 50 Gy delivered in 25 fractions over 5 weeks.
Treatment was delivered via two-dimensional radiation therapy, and median follow-up was 55 months, with an interquartile range of 36-79 months.
Locoregional recurrence rates were 8.3 percent following accelerated treatment and 8.1 percent following standard treatment, for a difference of 0.2 percent. Distant metastases occurred in 23.2 percent of women in the accelerated arm compared to 26.2 percent in the standard treatment cohort.
Five-year overall survival in both groups was 84.4 percent, while the disease-free survival rate was 72.7 percent. Five-year overall survival was 83.2 percent following accelerated treatment and 85.6 in the standard treatment group, and 5-year disease-free survival rates were 74.6 percent in the accelerated treatment arm versus 70.7 percent following standard treatment.
Out of 644 patients with ER and/or PR positive, 93.6 percent received hormonal therapy. With a median follow-up of 52 months (IQR, 39-79) for surviving patients, the 5-year cumulative incidence of locoregional recurrence was 92.8 percent.
In terms of treatment-related side effects, fewer women in the accelerated group experienced grade 3 acute skin toxicity (3.5% vs. 7.8% of standard-treatment patients), and rates were similar between the two groups for symptomatic radiation pneumonitis, lymphedema, and shoulder disorder. No patients experienced brachial plexopathy.
"Clinicians have seen clear benefits with accelerated radiation therapy to the whole breast after breast-conserving surgery, but questions remain about its safety and effectiveness with treating nodal regions," said Wang. "Our trial demonstrates a similar benefit for intermediate-stage breast cancer after mastectomy, in that we reduced treatment time from 5 weeks to 3 weeks while preserving high rates of tumor control and tolerability."
Commentary
ASTRO President Paul Harari, MD, FASTRO, Chairman of the Department of Human Oncology at the University of Wisconsin, Madison, said the study was powerful and important.
"Some of the most valuable trials are those that have simple designs, and this had a very simple design and found that hypofractionated treatment achieved a biological equivalent dose in 3 weeks' time. This is not brand-new to the world of radiation oncology of course; we have seen this in a variety of areas. Even in the breast conservation setting, we are seeing increasing use of accelerated radiation and hypofractionated techniques," noted Harari, who moderated the panel discussion.
"This is a powerful study in a part of the world where there is plenty of breast cancer and [provides] a simple solution for patients and providers or institutions that have very big waiting lists for machine use. For them, this is potentially a game-changing type of study, so I'm very optimistic about the implications."
While the technique is common for patients after lumpectomy who do not receive nodal radiation, hypofractionated radiation is not yet common in the U.S., noted Bruce Haffty, MD, MS, Chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey in New Brunswick.
"This study and other data will help to increase the utilization of hypofractionation in the setting of regional nodal radiation, but it will take some time before it becomes commonly adopted," he told Oncology Times.
There are some drawbacks, however, he noted. "Patients in this study all had mastectomy without reconstruction, and I think many will be reluctant to consider this in the reconstructed breast.
"This trial helps to address some of the reservations that many radiation oncologists have about hypofractionation to the regional nodes. No randomized studies directly addressing the issue have been done before, but many will want to see longer follow-up and additional studies."
A similar study comparing hypofractionation to standard fractionation in postmastectomy patients who have had reconstruction is just being launched, and Haffty is part of the Alliance for Clinical Trials in Oncology research team conducting the trial.
Kurt Samson is a contributing writer.