Ultra-Accelerated Photons, Protons or Brachytherapy for Favorable Early Breast Cancer: Long-Term Results of a 3-Fraction Partial Breast Irradiation Trial

Abstract

<h3>Purpose/Objective(s)</h3> To report long-term outcomes of a novel partial breast irradiation (PBI) regimen. We hypothesized that condensing treatment to 3 fractions and reducing total dose could improve the therapeutic ratio based on emerging evidence that breast cancer (BC) is more sensitive than surrounding normal tissues to high dose fractions. <h3>Materials/Methods</h3> We conducted a phase 2 trial of photon, proton, or brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years and s/p lumpectomy with negative sentinel nodes for estrogen receptor positive (ER+) invasive BC without preoperative chemotherapy or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically effective dose as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin and prescribed 21.9 Gy (RBE) in 3 fractions. Intracavitary brachytherapy was prescribed 21 Gy in 3 daily fractions. Radiotherapy was administered on 3 consecutive business days. Primary outcome was nurse-assessed adverse (fair/poor) cosmesis by 4-point Harvard scale at 3 years versus pre-PBI. Patients completed quality of life and self-reported cosmesis surveys. Adverse events were assessed using CTCAE, v 4.0. <h3>Results</h3> Between 2015 and 2017, 162 eligible patients were treated: photons in 56, protons in 49, and brachytherapy in 57. Median patient age was 67 years. 79% had invasive BC (all ER+) and 22% had DCIS (83% ER+). Median tumor size was 1.1 cm. Median Ki67 was 10% (IQR 6-17) and grade was 2-3 in 62%. The median of the mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons <0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. 55% received endocrine therapy. The proportion of patients with adverse cosmesis (by RN assessment) was 14.4% pre-PBI, 4.0% at 3 years, and 5.6% at last follow-up (at median 4.9 years) with six patients (3.8%, 3 photon, 3 brachytherapy) experiencing cosmetic worsening. 92.7%, 95.9%, and 94.7%, of patients in the photon, proton, and brachytherapy cohorts had good or excellent cosmesis at last follow-up. The proportion with adverse cosmesis by self-report was 0% pre-PBI and 2.0% at 3 years. Four patients developed local recurrence (1 photons, 2 protons, 1 brachytherapy). 5-year local recurrence-free, progression-free, and overall survival were 97.9%, 95.1%, and 96.9%, respectively. There were 2 treatment related grade ≥2 adverse events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life. <h3>Conclusion</h3> Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues, was associated with favorable cosmetic outcomes, disease control, and excellent tolerability. This is an attractive option for small node-negative ER+ BC and DCIS.