PHILADELPHIAIn a randomized trial, breast cancer patients who underwent postoperative intensity modulated radiation therapy (IMRT) had a markedly reduced incidence of moist desquamation and overall skin toxicity, compared with those receiving standard radiation therapy. Jean-Philippe Pignol, MD, PhD, reported the results at the 48th annual ASTRO meeting (plenary 1).
Furthermore, the unexpectedly rapid accrual of patients into the study indicates that "skin toxicity is very important to our patients," said Dr. Pignol, of Toronto Sunnybrook Regional Cancer Centre. An additional surprising finding was the high incidence of moist desquamation at 6 weeks, compared with previous studies that have followed patients for shorter intervals. This finding indicates a need to extend the customary period of follow-up after treatment.
Moist desquamation is known to develop at the location of radiation "hot spots," particularly in the inframammary fold. IMRT has been shown to result in a more uniform dose distribution than standard two-field radiation therapy with wedge compensation, but the clinical implications of this greater uniformity were not known. Dr. Pignol's study found large reductions in grade 2-4 skin toxicity and in moist desquamation in patients receiving IMRT.
The study enrolled 358 patients with early-stage breast cancer treated with local excision. The target enrollment was reached in 20 months, well ahead of the planned 3-year accrual period. Patients were randomly assigned to receive postoperative IMRT or standard wedge radiation, at doses of 50 Gy, with or without a 16-Gy boost. Randomization was stratified by breast size and boost.
Breast IMRT was associated with a 17% reduction in moist desquamation occurring at any location on the breast (31% vs 48% for wedge therapy, P = .002) and specifically in the inframammary crease (26% vs 43%, P = .001). Differences in grade 3-4 skin toxicity between groups were not significant, possibly owing to the variability in measuring these outcomes. But overall grade 2-4 toxicity was reduced by nearly 75% in patients receiving IMRT.
Risk of skin toxicity was related to breast size, with a threefold increase in incidence between women with small- and medium-size breasts and another threefold increase between medium and large. Skin toxicity was also related to the peak radiation dose received and to the sagittal gradient, a measure of the uniformity of radiation distribution in the sagittal plane. In a multivariate analysis, significant predictors of skin toxicity were the radiation method used and breast size.
The incidence of moist desquamation, almost 50% in the group receiving standard therapy, was surprisingly high, compared with previously reported rates of 20% to 38%, Dr. Pignol said. Only about half of cases occurred within the first few weeks of follow-up. This observation indicates that "moist desquamation is more frequent than expected and is often delayed," he said. In follow-up questionnaires, he noted, patients indicated that grade 2-4 moist desquamation was associated with increased pain and a poorer quality of life.