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

Study Details

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.

Toxicity

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.