Local-regional control of recurrent breast carcinoma after mastectomy: Does hyperfractionated accelerated radiotherapy improve local control?

Purpose: Hyperfractionated, accelerated radiotherapy (HART) has been advoca ted for patients with local-regionally recurrent breast cancer because it i s believed to enhance treatment effects in rapidly proliferating or chemore sistant tumors. This report examines the value of HART in patients with loc al-regionally recurrent breast cancer treated with multimodality therapy. Methods and Materials: The study included 148 patients with local-regionall y recurrent breast cancer after mastectomy, who were treated with definitiv e local irradiation and systemic therapy consisting of either tamoxifen, cy totoxic chemotherapy, or both, along with excision of the recurrent tumor w hen possible. Patients with distant metastases were excluded, except for tw o patients with ipsilateral supraclavicular nodal metastases. Patients rece ived comprehensive irradiation to the chest wall and regional lymphatics to a median dose of 45 Gy, with a boost to 60 Gy to areas of recurrence. Sixt y-eight patients (46%) were treated once daily at 2 Gy/fraction (fx), and 8 0 (54%) were treated twice daily at 1.5 Gy/fx. Forty-eight patients (32%), who had palpable gross disease that was unresponsive to systemic therapy an d/or unresectable, were irradiated. The median follow-up time of surviving patients was 78 months. Results: Overall actuarial local-regional control (LRC) rates at 5 and 10 y ears were 68% and 55%, respectively. Five- and ten-year actuarial overall s urvival (OS) and disease-free survival (DFS) rates were 50% and 35%, 39% an d 29%, respectively. Univariate analysis revealed that LRC was adversely af fected by 1. advanced initial American Joint Committee on Cancer (AJCC) sta ge (g 0.001), 2. clinically evident residual disease at time of treatment ( p < 0.0001), 3. more than three positive nodes at initial mastectomy (p 0.0 14), 4. short interval from mastectomy to recurrence (< 24 months, p 0.0007 ), 5. nuclear grade (III vs. I or II, p = 0.045), and 6. number of recurren t nodules (1 vs. > 1,p = 0.02). Patient age at time of recurrence (< 40 vs, greater than or equal to 40 years), recurrence location on the chest wall, estrogen receptor status, progesterone receptor status or menopausal statu s did not adversely affect LRC. On multivariate analysis, only clinically e vident residual disease at the time of treatment and short interval from ma stectomy to recurrence remained significant. When once-a-day irradiation wa s compared to the twice-a-day schedule, no significant differences were see n in LRC (67% vs. 68%), OS (47% vs. 52%), or DFS (42% vs. 36%) for the enti re group of patients at 5 years. Pairwise comparison of the two fractionati on schedules in each of the adverse outcome subgroups identified above show ed no clinically significant differences in LRC at 5 years. For the 48 pati ents who began radiotherapy with measurable gross local recurrence, the com plete response rate to radiotherapy was 73%, with no difference seen betwee n the two fractionation schedules. The incidence of acute and chronic radia tion-related complications was similar in both treatment groups. Conclusions: Hyperfractionated accelerated radiotherapy, although well tole rated by patients with local-regionally recurrent breast cancer, did not re sult in superior local-regional control rates when compared to daily fracti onated regimens. Alternative strategies, such as dose escalation or chemora diation, may be required to improve control. (C) 1999 Elsevier Science Inc.