Abstract Background: For many women with early-stage breast cancer, accelerated partial breast irradiation (APBI) offers comparable tumor control to whole-breast radiation with a shorter treatment course. However, cosmetic outcomes vary by technique. Stereotactic body radiotherapy (SBRT) is a promising external beam method allowing highly conformal dose delivery with tight margins, potentially improving cosmesis by sparing normal tissue. We present final three-year results from a prospective trial evaluating a five-fraction SBRT regimen for APBI, focusing on long-term safety, cosmesis, functional status, and local-regional control. Methods: Twenty-three patients with early-stage breast cancer (24 treatment plans) received 30 Gy in five daily fractions. A bioabsorbable 3D tissue marker (BioZorb™) was placed at lumpectomy for cavity delineation. Clinical target volume (CTV) included the cavity plus 1-cm margin; planning target volume (PTV) added 3 mm and was limited to ≤124 cc. Median PTV volume was 76.0 cm3 (range, 50.3–211.7). Treatment was delivered using 10-MV flattening filter-free beams on a Varian Edge system with VMAT planning and daily cone-beam CT. Positioning was prone or supine per anatomy; two patients had 9- and 11-day courses due to non-clinical delays. Zubrod status, patient- and nurse-reported cosmesis (4-point scale), adverse events, and imaging (mammography, ultrasound, MRI) were evaluated through 36 months. Results: At 36 months, 20 of 23 patients remained on protocol. One experienced biopsy-confirmed nodal recurrence at 6 months; two were lost to follow-up with benign or stable imaging. No ipsilateral breast tumor recurrences were observed. Zubrod status remained 0 in 90% at 36 months, with no grade ≥2 functional decline. Patient-reported cosmesis was excellent or good in 75% at 36 months (down from 85% baseline); nurse-reported was 80%, with stability across intervals. Poor cosmesis was reported by ≤2 patients at any timepoint. Fat necrosis affecting cosmesis occurred at 18 months but resolved. Erythema, pigment change, retraction, and volume loss were noted at 24 months but were typically non-cosmetic. Excellent/good cosmesis was maintained in ≥75% of patients across all intervals. Conclusion: This five-fraction SBRT approach to APBI was safe, well-tolerated, and preserved long-term cosmesis and function. Among patients completing 36-month follow-up, no ipsilateral breast tumor recurrences occurred. SBRT is a promising, efficient alternative to whole-breast radiation in carefully selected early-stage patients. Citation Format: M. Gevorgian, V. Reddy, T. Mathew, Y. Liu, C. Veale, D. Hablitz, H. Krontiras, A. Dalton, K. Meyers, M. Dobelbower, R. Lancaster, M. Bredel, C. Parker, K. Keene, E. Thomas, D. H. Boggs. Three-year outcomes following five-fraction sbrt for apbi in early-stage breast cancer: cosmesis, functional status, and local control 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 PS1-08-03.
Gevorgian et al. (Tue,) studied this question.