Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

Purpose: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. Methods and Materials: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. Results: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p = 0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p = 0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p = 0.54). Conclusion: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients.