February 10, 2010 — A hypofractionated 3-week schedule of whole-breast radiation is as effective as a conventional 5-week schedule in preventing local breast cancer recurrence at 10 years. Furthermore, the different approaches had similar rates of "good or excellent" cosmetic outcome.
These results, from a 1234-patient randomized controlled trial of the different radiation treatment schedules, are reported in the February 11 issue of the New England Journal of Medicine.
The 10-year cosmetic results of the study are especially important, say the authors, because "there was concern that late toxic effects of radiation associated with the hypofractionated regimen could develop."
Indeed, there was a worsening of cosmetic outcome over time, but the patients treated with hypofractionated radiation had cosmetic outcomes similar to those treated with the standard regimen, report the Canadian authors, led by Timothy Whelan, BM, BCh, from McMaster University and the Juravinski Cancer Center in Hamilton, Ontario.
Dr. Whelan and colleagues emphasized that the results are only applicable to the women in the study population: those with node-negative invasive breast cancer with clear margins after lumpectomy.
For those women, "an abbreviated course of radiation therapy should be more convenient and less costly than standard treatment," write Dr. Whelan and his coauthors.
The authors hope that the results will lead to an increase in the number of women who receive radiation after surgery. Currently, "up to 30% of women in North America" who have breast-conserving surgery do not receive any radiation, they say.
Another recent study, published online February 5 in The Lancet Oncology, extends the definition of outcomes in this treatment population. This study found that hypofractionated radiation for breast cancer produces "no detriment to body image."
The investigators, who are from the Standardization of Breast Radiotherapy (START) trials in the United Kingdom, assessed quality-of-life issues related to skin-tissue effects, which are not often evaluated in breast cancer, notes an accompanying editorial.
"These researchers show a consideration of the patient's point of view that is too often absent," writes editorialist Julie Schnur, PhD, from Mount Sinai School of Medicine in New York City, about the British study.
Cosmetics Are the Same
In the Canadian study, women with node-negative invasive breast cancer were randomized to either standard whole-breast irradiation (50 Gy given in 25 fractions over a period of 35 days) or accelerated hypofractionated irradiation (42.5 Gy given in 16 fractions over a period of 22 days).
The risk for local recurrence at 10 years was 6.7% among the 612 women in the standard-treatment group and 6.2% among the 622 women in the hypofractionated-treatment group (absolute difference, 0.5 percentage points; 95% confidence interval [CI], –2.5 to 3.5).
There were 126 deaths in the standard-treatment group and 122 in the hypofractionated-treatment group. "The probability of survival over time was similar in the 2 groups (P = .79)" write the authors.
At 10 years, 71.3% of the women in the standard-treatment group and 69.8% in the hypofractionated-treatment group had good or excellent cosmetic outcomes (absolute difference, 1.5 percentage points; 95% CI, –6.9 to 9.8).
With regard to toxic effects and cosmetic outcome, the "global cosmetic outcome worsened over time," but there were no significant differences between the 2 treatment groups at any time, the authors write.
In the long term, radiation therapy can cause telangiectasia and fibrosis of subcutaneous tissue, note the authors. These lead to "loss of volume and retraction of the breast," which adversely affect cosmetics.
The authors note that women with large breasts were not included in the study, and that "few women" received adjuvant chemotherapy as part of their treatment.
Overall, the 10-year efficacy and toxicity results of this Canadian trial are "consistent" with 5-year results from a pair of British trials, START A and START B, say Dr. Whelan and his colleagues.
Better Quality of Life
Conducted in the United Kingdom, START A compared 2 different hypofractionation schedules (39 Gy and 41.6 Gy) given over 5 weeks with standard radiation (Lancet Oncol. 2008;9:331-341); START B compared a single schedule (40 Gy) given over 3 weeks with standard radiation (Lancet. 2008;371:1098-1107). Standard radiation was 50 Gy given in 25 fractions.
Since publishing their efficacy and toxicity data, the START researchers went on to analyze patient-reported quality-of-life issues from both the A and B trials, and these are the findings now reported in the Lancet Oncology.
Specifically, they compared the different radiotherapy regimens with respect to changes in breast, arm, shoulder symptoms, and in function and body image.
Over the 5 years of the studies, the most frequently reported adverse effects were breast hardness (41%) and change in breast appearance (39%), report the START investigators, led by Penelope Hopwood, MD, from the Institute of Cancer Research in Sutton, United Kingdom.
For most of the adverse effects, hypofractionated schedules had rates that were lower than or similar to standard radiation.
Adverse change in skin appearance after radiotherapy was the only symptom to differ significantly between the radiotherapy schedules — and the patients treated with hypofractionated radiation had better outcomes.
Specifically, adverse change in skin appearance was significantly lower for patients who received 39 Gy than for those who received the standard 50 Gy (hazard ratio [HR], 0.63; 95% CI, 0.47 to 0.84), and for those who received 40 Gy than for those who received the standard 50 Gy (HR, 0.76; 95% CI, 0.60 to 0.97).
No significant difference was observed between patients who received 41.6 Gy and those who received the standard 50 Gy (HR, 0.83; 95% CI, 0.63 to 1.08).
More research examining quality of life and radiotherapy outcomes is needed, writes Dr. Schnur in her editorial accompanying the study.
"The study of quality of life as it relates to normal tissue effects in patients with breast cancer is woefully understudied," she notes.
The Canadian study was supported by grants from the Canadian Breast Cancer Research Alliance and the Canadian Cancer Society. The START study had support from Cancer Research UK, the UK Medical Research Council, and the UK Department of Health. For both studies, the researchers have disclosed no relevant financial relationships.
N Engl J Med. 2010;362:513-520.
Lancet Oncol. 2010. Published onlineFebruary 5, 2010. Abstract, Abstract
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