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The primary objective is to systematically improve organ-at-risk sparing through automated and reproducible optimization of planning constraints while maintaining clinically acceptable target coverage. An OFV-guided optimization workflow was empirically developed using a separate sensitivity dataset and subsequently evaluated in 20 clinical breast cancer patients (13 left-sided, 7 right-sided). The automated Python-based framework iteratively adapts MaxEUD constraints during optimization until dose metrics converge, without manual intervention. Automatically generated plans were compared to clinically delivered VMAT plans using target coverage, dose\u2013volume metrics, and monitor units as a surrogate for delivery efficiency. The automated approach consistently achieved significant reductions in mean organ doses and low-dose volumes (e.g.,\n                    <jats:inline-formula>\n                      <jats:tex-math>$$V_{2Gy}$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ,\n                    <jats:inline-formula>\n                      <jats:tex-math>$$V_{5Gy}$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ) while preserving PTV coverage. Mean heart dose decreased from\n                    <jats:inline-formula>\n                      <jats:tex-math>$$3.09 \\pm 1.06$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    \u00a0Gy to\n                    <jats:inline-formula>\n                      <jats:tex-math>$$2.21 \\pm 0.69$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    \u00a0Gy for left-sided cases and from\n                    <jats:inline-formula>\n                      <jats:tex-math>$$1.88 \\pm 1.06$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    \u00a0Gy to\n                    <jats:inline-formula>\n                      <jats:tex-math>$$1.17 \\pm 0.25$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    \u00a0Gy for right-sided cases (\n                    <jats:inline-formula>\n                      <jats:tex-math>$$p &lt; 0.001$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ). Significant dose reductions were also observed for the ipsilateral lung, contralateral lung, and contralateral breast, accompanied by a 16.9\u00a0% reduction in monitor units (\n                    <jats:inline-formula>\n                      <jats:tex-math>$$p &lt; 0.001$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ) and reduced inter-patient variability. In contrast, no statistically significant difference was observed for lung\n                    <jats:inline-formula>\n                      <jats:tex-math>$$V_{20Gy}$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    . In conclusion, OFV-guided VMAT optimization enables reproducible and systematic improvement of organ-at-risk sparing in breast radiotherapy. By reducing organ doses, low-dose burden, monitor units, and inter-patient variability without compromising target coverage, the proposed framework could provide a robust and standardized baseline for clinical VMAT planning and a consistent foundation for future data-driven and machine-learning\u2013based optimization approaches.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-52616-2","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:34:08Z","timestamp":1779366848000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Objective-function-guided automated VMAT planning reduces OAR dose, low-dose exposure, and inter-planner variability in breast radiotherapy"],"prefix":"10.1038","volume":"16","author":[{"given":"Hannes","family":"Rennau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Hildebrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"issue":"1","key":"52616_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717X-5-110","volume":"5","author":"J Alvarez-Moret","year":"2010","unstructured":"Alvarez-Moret, J., Pohl, F., Koelbl, O. & Dobler, B. 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