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Conventional preclinical models, including two\u2010dimensional (2D) cell cultures and murine xenografts, exhibit significant limitations in recapitulating human tumor pathophysiology, thereby impeding the clinical translation of novel radiotherapeutic strategies. Patient\u2010derived organoids (PDOs) have emerged as transformative three\u2010dimensional (3D) ex\u00a0vivo models that recapitulate key aspects of original tumor heterogeneity and are increasingly applied in oncology research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This article provides a comprehensive review of the literature on the application of PDOs in radiation oncology, with a focused analysis of their pathway toward clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PDOs demonstrate significant utility in predicting radiosensitivity, elucidating radioresistance mechanisms, optimizing combination therapies, modeling radiation injury, and screening targeted drugs. The integration of organoid technology with microfluidic organ\u2010on\u2010a\u2010chip (OoC) platforms also offers unprecedented capability to dynamically simulate the tumor microenvironment and conduct high\u2010throughput dose\u2010response studies. A translational roadmap is presented for leveraging these biomimetic systems to advance personalized radiotherapy, ultimately aiming to accelerate the clinical translational application of organoids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Despite challenges in standardization and immune component recapitulation, PDOs represent a powerful platform for advancing personalized radiotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72251","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:56:00Z","timestamp":1789102560000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Organoids in Precision Radiotherapy: Methodological Foundations, Tumor\u2010Specific Evidence, and Translational 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Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Soochow University  Suzhou Jiangsu 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