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Med."],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The current standard-of-care (SOC) practice for defining the clinical target volume (CTV) for radiation therapy (RT) in patients with glioblastoma still employs an isotropic 1\u20132\u2009cm expansion of the T2-hyperintensity lesion, without considering the heterogeneous infiltrative nature of these tumors. This study aims to improve RT CTV definition in patients with glioblastoma by incorporating biologically relevant metabolic and physiologic imaging acquired before RT along with a deep learning model that can predict regions of subsequent tumor progression by either the presence of contrast-enhancement or T2-hyperintensity. The results were compared against two standard CTV definitions. Our multi-parametric deep learning model significantly outperformed the uniform 2\u2009cm expansion of the T2-lesion CTV in terms of specificity (0.89\u2009\u00b1\u20090.05 vs 0.79\u2009\u00b1\u20090.11; <jats:italic>p<\/jats:italic>\u2009=\u20090.004), while also achieving comparable sensitivity (0.92\u2009\u00b1\u20090.11 vs 0.95\u2009\u00b1\u20090.08; <jats:italic>p<\/jats:italic>\u2009=\u20090.10), sparing more normal brain. Model performance was significantly enhanced by incorporating lesion size-weighted loss functions during training and including metabolic images as inputs.<\/jats:p>","DOI":"10.1038\/s41746-025-01861-2","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T06:47:08Z","timestamp":1754549228000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel radiotherapy target definition using AI-driven predictions of glioblastoma recurrence from metabolic and diffusion MRI"],"prefix":"10.1038","volume":"8","author":[{"given":"Nate","family":"Tran","sequence":"first","affiliation":[]},{"given":"Tracy L.","family":"Luks","sequence":"additional","affiliation":[]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[]},{"given":"Angela","family":"Jakary","sequence":"additional","affiliation":[]},{"given":"Jacob","family":"Ellison","sequence":"additional","affiliation":[]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[]},{"given":"Oluwaseun","family":"Adegbite","sequence":"additional","affiliation":[]},{"given":"Devika","family":"Nair","sequence":"additional","affiliation":[]},{"given":"Pranav","family":"Kakhandiki","sequence":"additional","affiliation":[]},{"given":"Annette M.","family":"Molinaro","sequence":"additional","affiliation":[]},{"given":"Javier E.","family":"Villanueva-Meyer","sequence":"additional","affiliation":[]},{"given":"Nicholas","family":"Butowski","sequence":"additional","affiliation":[]},{"given":"Jennifer L.","family":"Clarke","sequence":"additional","affiliation":[]},{"given":"Susan M.","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Steve E.","family":"Braunstein","sequence":"additional","affiliation":[]},{"given":"Olivier","family":"Morin","sequence":"additional","affiliation":[]},{"given":"Hui","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Janine M.","family":"Lupo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"1861_CR1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp, R. et al. 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