Intraoperative or postoperative radiotherapy boost in high-risk breast cancer: a matched-pair analysis

PURPOSE: The optimal boost technique following breast-conserving surgery for patients with high-risk early breast cancer remains controversial. This study compared oncologic outcomes following an intraoperative radiotherapy (IORT) boost using low-energy X‑rays with those of a conventional external beam radiotherapy (EBRT) boost in a matched-pair cohort. METHODS: Patients treated with breast-conserving surgery followed by either an upfront IORT boost (20 Gy prescribed to the applicator surface) or a postoperative EBRT boost (16 Gy in 8 fractions), sequentially after whole-breast radiotherapy, between 2014 and 2019 were retrospectively identified from a prospectively maintained institutional database. Whole-breast irradiation was delivered after IORT using either conventional or moderately hypofractionated schedules according to institutional practice. The primary endpoint was ipsilateral breast tumour recurrence (IBTR). Secondary endpoints included nodal recurrence, distant metastasis, overall survival (OS), and breast cancer-specific survival (BCSS). Time-to-event outcomes were estimated using the Kaplan-Meier method, whereas treatment comparisons were performed using Cox proportional hazards regression with robust sandwich variance estimates clustered by matched pair. RESULTS: Following 1:1 matching, 400 patients (200 per group) were included. After a median follow-up of 58 months, the cumulative incidence of local recurrence was 3.5% and 2.0%, respectively, with no statistically significant difference between treatment groups (HR 1.80, 95% CI 0.58-5.58; p = 0.312). Likewise, no significant differences were observed for nodal recurrence-free survival (HR 0.98, 95% CI 0.19-5.16; p = 0.980), distant metastasis-free survival (HR 0.92, 95% CI 0.38-2.23; p = 0.859), breast cancer-specific survival (HR 0.79, 95% CI 0.30-2.10; p = 0.634), or overall survival (HR 1.19, 95% CI 0.59-2.40; p = 0.636). CONCLUSIONS: In this matched-pair analysis, an intraoperative low-energy X‑ray boost achieved oncologic outcomes comparable to those of a conventional postoperative EBRT boost in patients undergoing breast-conserving therapy for high-risk early breast cancer. These findings support IORT boost as an effective and well-tolerated alternative that may simplify treatment delivery without compromising long-term oncologic outcomes.