Simple SummaryCompared to whole-breast irradiation, partial-breast irradiation uses smaller radiotherapy volumes and usually leads to lower radiation doses to the healthy tissues, such as the heart and lungs. For the first time, the present evaluation offers a complete analysis of the doses to on whole-breast irradiation. The dose reduction to the healthy organs was significant in favor of partial-breast irradiation. Therefore, partial-breast irradiation should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.AbstractIn order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy,p= 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy,p= 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy,p= 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy,p= 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%,p< 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy,p< 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy,p= 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy,p= 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.