As reported in The Lancet by Timothy J. Whelan, BM, BCh, and colleagues, the phase III noninferiority RAPID trial has shown that external-beam accelerated partial-breast irradiation is noninferior to whole-breast irradiation in reducing risk of local recurrence after breast-conserving surgery in women with ductal carcinoma in situ (DCIS) or node-negative breast cancer. External-beam accelerated partial-breast irradiation was associated with greater moderate late toxicity and adverse cosmesis outcomes.

“External-beam accelerated partial-breast irradiation was noninferior to whole-breast irradiation in preventing ipsilateral breast tumor recurrence. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment.”

— Timothy J. Whelan, BM, BCh, and colleagues

Tweet this quote

Study Details

The open-label trial included 2,135 women with microscopically clear surgical margins and negative axillary lymph nodes from 33 sites in Canada, Australia, and New Zealand. Patients were randomly assigned between February 2006 and July 2011 to receive external-beam accelerated partial-breast irradiation (n = 1,070) or whole-breast irradiation (n = 1,065). Patients with isolated tumor cells or micrometastases ≤ 2 mm in the lymph nodes were eligible.

Accelerated partial-breast irradiation consisted of 38.5 Gy in 10 fractions twice per day over 5 to 8 days; whole-breast irradiation consisted of 42.5 Gy in 16 fractions once per day over 21 days or 50 Gy in 25 fractions once per day over 35 days. The primary outcome measure was ipsilateral breast tumor recurrence in the intention-to- treat population. Noninferiority was declared if the upper limit of the two-sided 90% confidence interval (CI) for the observed hazard ratio (HR) was < 2.02.

Ipsilateral Breast Tumor Recurrence Risk

Median follow-up was 8.6 years. The 8-year cumulative rates of ipsilateral breast tumor recurrence were 3.0% (95% CI = 1.9%–4.0%) in the accelerated partial-breast irradiation group vs 2.8% (95% CI = 1.8%–3.9%) in the whole-breast irradiation group; the hazard ratio was 1.27, with a 90% confidence interval of 0.84 to 1.91, which met the noninferiority criterion. Nonbreast second cancers occurred in 7.9% vs 5.4% of patients.

Toxicity

Acute radiation toxicity—defined as grade ≥ 2 occurring within 3 months of the start of radiotherapy—occurred in 28% of patients in accelerated partial-breast irradiation group vs 45% of the whole-breast irradiation group (P < .0001). Late radiation toxicity (grade ≥ 2, > 3 months) occurred in 32% vs 13% of patients (P < .0001). Adverse (fair or poor) cosmesis outcomes were self-reported by 27% vs 18% of patients at 3 years, 30% vs 18% at 5 years, and 31% vs 15% at 7 years.

The investigators concluded, “External-beam accelerated partial-breast irradiation was noninferior to whole-breast irradiation in preventing ipsilateral breast tumor recurrence. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied.”

Dr. Whelan, of McMaster University and Juravinski Cancer Centre, Hamilton, is the corresponding author for The Lancet article.

Disclosure: The study was funded by the Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance. For full disclosures of the study authors, visit thelancet.com.