Abstract Background: Hypo-fractionated radiation therapy (HFRT) for breast cancer has been shown to have comparable local control and toxicity to conventional fractionation (CF) whole breast irradiation (WBI). Tumor bed boost improves local tumor control and can be delivered either sequentially (SB) or concomitantly (CB) with WBI. Initial results from NRG RTOG 1005 reported CB with HFRT over 15 fractions (F) was non-inferior to SB after HFRT or CF WBI in terms of in-breast recurrence (IBR), adverse events (AE), and cosmesis, with the added benefit of reduction of overall treatment time. We report outcomes of HFRT with CB in patients with invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS), with majority treated in prone position at our institution. Methods: We retrospectively identified patients with early-stage, clinically node-negative IBC and DCIS treated with HFRT WBI with CB to the lumpectomy cavity from 2013 to 2025. All underwent breast-conserving surgery followed by WBI 40 Gy, plus a CB to lumpectomy cavity of 48 Gy, delivered in 15 F over 3 weeks using 3D conformal (3DCRT). Patient demographics, clinical characteristics, and treatment details were collected from electronic medical records. Ipsilateral breast recurrence (IBR), Disease-free survival (DFS), overall survival (OS), breast cancer specific survival, radiation toxicities, and cosmesis outcomes were recorded. Radiation toxicities were graded using CTCAE v4.0, and physician-reported cosmetic outcomes were categorized as excellent/good versus fair/poor according to the NRG-RTOG Global Cosmetic Score. Results: A total of 407 patients (343 IBC, 64 DCIS) met inclusion criteria; 74 were 50 years of age. Median age was 60 years (IQR: 52-68) and median follow-up was 39 months. Higher risk clinical features included ER- (26.3%), T2 (20.4%), positive margins (3.2%), and grade 3 (43.8%). Most patients (95%) were treated in prone position. 39.6% patients received chemotherapy and 67.1%, endocrine therapy. The most common acute adverse events (AEs) were grade 1 radiation dermatitis (58%), fatigue (63.1%), and breast pain (28.3%). Most frequent late AEs were grade 1 fatigue (21%), breast edema (18.8%), hyperpigmentation (42.5%), fibrosis (20.4%), and atrophy (9.4%) at 6 months, and 15.1%, 14.9%, 28.4%, 21.7%, and 15.1%, respectively, at 1 year. No patients developed grade ≥3 toxicity. At 1 and 3 years, excellent/good cosmesis was observed in 96% and 89% of patients, and fair outcomes in 4% and 11%, respectively, among patients with available data. No poor cosmetic outcomes were observed. Acute and late adverse events, as well as cosmetic outcomes (p-value of 0.777 at 1 year and p-value of 0.364 at 3 years, respectively), were comparable between patients aged 50 and ≥50 years. Three-year IBR was 0.98%. Three and five-year DFS/OS were 98.3%/97.5% and 97.5%/94.7%, respectively. 5-year breast cancer specific survival was 98.9%. Conclusion: The combination of HFRT with concomitant boost offers a promising approach to treatment for early-stage invasive breast cancer and DCIS, providing excellent local control with minimal toxicity and favorable cosmetic outcomes. This study presents real-world experience from a single institution on HFRT with CB to lumpectomy cavity for breast radiation. Citation Format: P. Kumar, T. Jitwatcharakomol, J. Schoenhals, A. Crum, S. Daniel, M. Mestres-Villanueva, G. Yevgeniya, T. Pathmarajah, T. Y. Andraos, R. Young, J. M. Eckstein, J. R. White, J. G. Bazan, E. H. Healy, S. Jhawar, S. J. Beyer. Hypofractionated Whole Breast Irradiation with Concomitant Boost following Breast Conservation Surgery in Early-Stage Breast Cancer 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 PS4-08-22.
Kumar et al. (Tue,) studied this question.