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Purpose or Objective: Operable patients with locoregional (LR) recurrent breast cancer at high risk for re-recurrence are treated with postoperative re-irradiation combined with hyperthermia (HT), i.e. heating the target area to 40-43 °C for one hour, in the Netherlands. Early 2015, national consensus was reached using a new standard RT dose fractionation schedule of 23x2Gy, replacing the 8x4Gy RT schedule used in our center. We investigated the impact of both postoperative re-irradiation schedules combined with HT on LR control and late toxicity in patients with LR recurrent breast cancer treated at our center. Materials and Methods: In this retrospective study, 112 women with resected LR recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation combined with 4-5 weekly HT sessions were included. RT treatment consisted of 8x4Gy (n=34, twice a week) until 2014, or 23x2Gy (n=78, 5 times a week) after 2014. Due to frailty or long travel distance 5 patients received 8x4Gy after 2014. Re-irradiation was delivered using 3 consecutive different RT planning techniques. From 2010 to mid-2014 the lateral chest wall and/or regional lymph nodes areas were irradiated using two opposing AP-PA fields and the anterior chest wall with electrons, the breast was treated with two tangential fields. From mid-2014 IMRT was applied using 5-7 beam angles, and from early 2016 onward VMAT using two (counter)clockwise partial arcs. Actuarial LR control and grade 2-5 late toxicity incidence (>3 months after the first re-irradiation fraction) were analyzed. Toxicity was defined according to CTC-AE v5.0. Patients had multiple late toxicities. The cause of late toxicity might be current or previous treatments or an cumulative effect. Backward multivariable Cox regression was performed. Results: Twenty-four patients (21.4%) developed an in-field recurrence. Median FU was 43 months (range 1-107 months). Threeyear LR control was 89.4% vs. 68.7% in the 23x2Gy and 8x4Gy group, respectively (p=0.01), LR control tended to be better for the 23x2Gy group after long FU (p=0.094; Fig 1A). In multivariate analysis, distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and thermal dose (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LR control. Three-year late grade 2, 3 and 4 toxicity was 63%, 39% and 0% vs. 54%, 19% and 8% for 23x2Gy and 8x4Gy groups, respectively. No grade 5 late toxicity occurred. The 23x2Gy group had a trend for more grade 3-4 late toxicity (p=0.064, Fig1B). Conclusion: Patients with LR recurrent breast cancer treated with 23x2Gy postoperative re-irradiation and HT tended to have better LR control at the cost of higher incidence of grade 3-4 late toxicity compared to patients treated with 8x4Gy.