Dose Deintensified 3-Day Photon, Proton, or Brachytherapy: A Nonrandomized Controlled Partial Breast Irradiation Trial

Abstract

Purpose: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy.

Methods and materials: A multicenter nonrandomized controlled trial with the primary outcome of adverse cosmesis at 3 years versus before PBI. Eligibility criteria were age ≥50 years treated with breast-conserving surgery for node-negative estrogen receptor-positive (ER+) invasive breast cancer or any ductal carcinoma in situ (DCIS) measuring ≤2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (relative biological effectiveness) and brachytherapy 21 Gy in 3 fractions. Radiation therapy technique and adjuvant endocrine therapy were selected at physician and patient discretion.

Results: Between June 17, 2015, and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. One hundred twenty-six (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). Fifty-four percent of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to the prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline and 2.3% at 3 years (difference, -12.2%; 95% CI, -100% to -6.4%). Adverse cosmesis at the last follow-up, with a median follow-up of 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient-reported outcomes, and just 2 grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. Five-year local recurrence-free survival and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences among 60 patients with invasive breast cancer and Ki67 ≤13.25%.

Conclusions: Deintensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the prespecified criteria for acceptability. This approach is an attractive option for patients with small node-negative ER+ breast cancer and DCIS.