Abstract Introduction: Intraoperative radiation therapy (IORT) delivered during breast-conserving surgery may streamline treatment and enhance cosmetic outcomes. However, optimal patient selection criteria remain uncertain, especially in Asian populations, where international guidelines may not be fully applicable. This study aimed to evaluate local recurrence rates, identify key prognostic factors, and assess the impact of supplemental external beam radiation therapy (EBRT) in Taiwanese patients receiving IORT. Methods: This retrospective analysis included 1,306 Taiwanese patients who underwent IORT between June 2014 and December 2021. Patients were stratified into low-risk and high-risk groups based on institutional criteria. Low-risk patients were those meeting all of the following: age ≥ 45 years, tumor size ≤ 3.5 cm, negative nodal involvement, Ki-67 ≤ 30%, hormone receptor (HR) positivity, and HER2 negativity. Patients who did not meet one or more of these criteria were classified as high-risk and were recommended to receive supplemental external beam radiation therapy (EBRT) following IORT. Results: In our cohort of 1,306 patients, the 3-year disease-free survival rate was 93.11% (95% CI: 91.6%-94.4%), with 87 patients (6.89%) experiencing recurrence. The median age was 52 years, and the median follow-up duration was 30.5 months. The overall local recurrence rate was 9.3%, which declined to 1.78% after excluding patients who did not receive indicated adjuvant therapies. Multivariable analysis identified Ki-67 30%, omission of hormone therapy, and omission of recommended EBRT as significant predictors of local recurrence, whereas age 45 was not independently associated with increased risk. Among high-risk patients, the addition of EBRT was associated with a 48.8% reduction in recurrence, achieving outcomes comparable to those of low-risk patients. Conclusions: Age alone should not determine IORT eligibility. A multifaceted approach, including tumor biology and adherence to recommended therapies, is essential. Supplemental EBRT improves outcomes in high-risk patients, and adapting guidelines may enhance patient selection in Asian populations. Citation Format: S. Shih, H. Takahashi, F.-M. Chen, J.-Y. Kan, L.-C. Kao, P.-F. Yang, C.-L. Li, C.-N. Kao, C.-Y. Kuo, C.-H. Chuang, M.-F. Hou, J.-Y. Tang. Factors Impacting Local Relapse Risk and Disease-Free Survival of Early Breast Cancer receiving Intraoperative Radiation Therapy in Taiwan 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 PS2-04-24.
Shih et al. (Tue,) studied this question.