Abstract Background: Accelerated partial breast irradiation (APBI) has demonstrated non-inferior in-breast recurrence rates compared to whole breast irradiation in low-risk hormone receptor positive breast cancer patients across multiple randomized clinical trials. Optimal external beam APBI fractionation, dosing, and technique, however, remain undefined. This study evaluated outcomes of two APBI regimens used at our institution: 28.5 Gy in 5 once-daily fractions on non-consecutive days and 38.5 Gy in 10 twice-daily (BID) fractions. Methods: This retrospective, single-institution study included post-menopausal women with ductal carcinoma in-situ (DCIS) and early-stage hormone receptor positive invasive breast cancer who underwent lumpectomy followed by APBI. Outcomes of interest include ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS), overall survival (OS), radiation toxicities (graded by CTCAE v5.0), and physician-reported (Harvard scale) cosmetic outcomes. Results: Patients treated with APBI between January 2017 and March 2025 were included. Total patients were 399: 257 in the 28.5 Gy group and 142 in the 38.5 Gy group. The median age was 66 years (IQR 59-72). Most patients were White (86.9%) and non-Hispanic (99.2%). The majority had T1 tumors (79.4%) or DCIS (18%), Grade 1-2 histology (93.5%), no lymphovascular invasion (96.5%), were ER-positive (98.5%), and PR-positive (93.5%). For invasive cases, HER-2 was negative in 98.8%. Baseline characteristics were similar between groups. The majority of patients received radiation using 3D-conformal technique (99.2%), in the prone position (96%), and started adjuvant endocrine therapy (86%). Based on 408 lesions, the median gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) were 19.6 cc, 113.2 cc, and 194.3 cc, respectively. Larger CTV and PTV values were observed in the 38.5 Gy group compared to the 28.5 Gy group: CTV (118.2 cc vs. 108.3 cc, p = 0.02) and PTV (208.6 cc vs. 183.3 cc, p 0.01). With a median follow-up of 3.4 years, the 3-year IBTR for 28.5Gy was 2% and 38.5Gy was 1%, p-value = 0.46. The 3-year DFS was 98% in the 28.5 Gy group and 99% in the 38.5 Gy group, p-value = 0.79 and the 3-year OS was 99% in both groups, p = 0.53. For acute toxicity, grade 1-2 dermatitis was significantly more common in the 38.5 Gy group (61.7% vs. 28.6%, p 0.01). For late toxicity at 1-year post-treatment, grade 1-2 skin hyperpigmentation (79.5% vs. 32.4%, p 0.01) and fibrosis (81.6% vs. 51%, p 0.01) were significantly more common in the 38.5 Gy group than 28.5 Gy group, respectively. Radiation dose of 38.5 Gy in 10 BID fractions was associated with significantly higher odds of developing fibrosis (adjusted odds ratio 4.15, 95% CI: 1.7-10.1) compared to 28.5 Gy daily fractionation. No grade ≥3 acute or late toxicities were observed. Physician-reported (Harvard scale) cosmetic outcomes were similar between groups. At 1-year, cosmetic outcomes were available for 304 patients. Excellent or good cosmesis was observed in 98.1% of patients in the 28.5 Gy group and 99% in the 38.5 Gy group, p-value = 0.15. At 3-year, cosmetic outcomes were available for 90 patients. Excellent or good cosmesis was 94.1% (28.5 Gy group) and 97.2% (38.5 Gy group), p-value = 0.83. Conclusions: Both regimens—28.5 Gy in 5 once-daily fractions and 38.5 Gy in 10 twice-daily fractions—delivered using 3D-conformal technique in the prone position yielded excellent outcomes in patients with low-risk breast cancer. However, the 28.5 Gy regimen demonstrated a lower incidence of acute and late toxicity and may be preferable in this patient population given its lower skin toxicity and increased convenience. Longer follow-up is warranted to confirm these findings. Citation Format: T. Jitwatcharakomol, Y. Gokun, S. Daniel, M. Mestres-Villanueva, R. Young, J. Eckstein, T. Andraos, E. Healy, J. White, J. Bazan, E. Cochran, S. Beyer, S. Jhawar. Outcomes of Once Daily and Twice Daily APBI Regimens in Hormone Receptor Positive Breast Cancer: A Single Institution Experience abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-07-20.
Jitwatcharakomol et al. (Tue,) studied this question.