As reported in The Lancet by Frank A. Vicini, MD, and colleagues, 10-year follow-up in the phase III NSABP B-39/RTOG 0413 equivalence trial has shown that accelerated partial-breast irradiation did not achieve equivalence to whole-breast irradiation in preventing local recurrence in women receiving breast-conserving therapy for early breast cancer.
Frank A. Vicini, MD
The open-label trial included 4,216 women from 154 sites in the United States, Canada, Ireland, and Israel with early-stage disease (stage 0, I, or II, no evidence of distant metastases but up to three positive axillary nodes permitted; tumor size ≤ 3 cm; all histologies and multifocal breast cancers permitted) who had lumpectomy with negative surgical margins. Patients were randomly assigned between March 2005 and April 2013 to receive whole-breast irradiation (n = 2,109) or accelerated partial-breast irradiation (n = 2,107). Among these, 2,036 patients in the whole-breast irradiation group and 2,089 in the accelerated partial-breast irradiation group were evaluable for the primary outcome.
Whole-breast irradiation consisted of 25 daily fractions of 50 Gy over 5 weeks with or without a supplemental boost to the tumor bed; accelerated partial-breast irradiation consisted of 34 Gy of brachytherapy or 38.5 Gy of external-beam radiation therapy in 10 fractions over 5 treatment days within an 8-day period. The primary outcome measure was invasive and noninvasive ipsilateral breast tumor recurrence as first recurrence in the intention-to-treat population. For equivalence of accelerated partial- vs whole-breast irradiation to be claimed, the 90% confidence interval of the observed hazard ratio had to be between 0.667 and 1.5.
Ipsilateral Breast Tumor Recurrence Risk
At a median follow-up of 10.2 years, ipsilateral breast tumor recurrence had occurred in 90 patients in the accelerated partial-breast irradiation group (4%) vs 71 patients in the whole-breast irradiation group (3%); the hazard ratio was 1.22 with a 90% confidence interval of 0.94–1.58, which failed to meet the equivalence test. The 10-year cumulative incidence of ipsilateral breast tumor recurrence was 4.6% in the accelerated partial-breast irradiation group vs 3.9% in the whole-breast irradiation group. Death from recurrent breast cancer occurred in 2% vs 2% of patients.
The highest adverse event grades reported in the accelerated partial-breast irradiation vs whole-breast irradiation groups were grade 1 in 40% vs 31%, grade 2 in 44% vs 59%, grade 3 in 10% vs 7%, and grade 4 or 5 in < 1% vs < 1%. No treatment-related deaths were observed. At least one second primary cancer occurred in 192 patients (9%) in the accelerated partial-breast irradiation group vs 200 (10%) in the whole-breast irradiation group (P = .46).
The investigators concluded, “Accelerated partial-breast irradiation did not meet the criteria for equivalence to whole-breast irradiation in controlling ipsilateral breast tumor recurrence for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different accelerated partial-breast irradiation techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of ipsilateral breast tumor recurrence, accelerated partial-breast irradiation might be an acceptable alternative for some women.”
Dr. Vicini, of 21st Century Oncology, Michigan Healthcare Professionals, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.