{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:22:21Z","timestamp":1787595741442,"version":"build-2736575974"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1146","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BJR"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:sec><jats:title>Objectives:<\/jats:title><jats:p> Glioblastoma (GBM) is the most common malignant primary brain tumor with local recurrence after radiotherapy (RT), the most common mode of failure. Standard RT practice applies the prescription dose uniformly across tumor volume disregarding radiological tumor heterogeneity. We present a novel strategy using diffusion-weighted (DW-) MRI to calculate the cellular density within the gross tumor volume (GTV) in order to facilitate dose escalation to a biological target volume (BTV) to improve tumor control probability (TCP). <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> The pre-treatment apparent diffusion coefficient (ADC) maps derived from DW-MRI of ten GBM patients treated with radical chemoradiotherapy were used to calculate the local cellular density based on published data. Then, a TCP model was used to calculate TCP maps from the derived cell density values. The dose was escalated using a simultaneous integrated boost (SIB) to the BTV, defined as the voxels for which the expected pre-boost TCP was in the lowest quartile of the TCP range for each patient. The SIB dose was chosen so that the TCP in the BTV increased to match the average TCP of the whole tumor. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> By applying a SIB of between 3.60 Gy and 16.80 Gy isotoxically to the BTV, the cohort\u2019s calculated TCP increased by a mean of 8.44% (ranging from 7.19 to 16.84%). The radiation dose to organ at risk is still under their tolerance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p> Our findings indicate that TCPs of GBM patients could be increased by escalating radiation doses to intratumoral locations guided by the patient\u2019s biology (i.e., cellularity), moreover offering the possibility for personalized RT GBM treatments. <\/jats:p><\/jats:sec><jats:sec><jats:title>Advances in knowledge:<\/jats:title><jats:p> A personalized and voxel level SIB radiotherapy method for GBM is proposed using DW-MRI, which can increase the tumor control probability and maintain organ at risk dose constraints. <\/jats:p><\/jats:sec>","DOI":"10.1259\/bjr.20220384","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T13:46:11Z","timestamp":1682603171000},"source":"Crossref","is-referenced-by-count":5,"title":["Isotoxic dose escalated radiotherapy for glioblastoma based on diffusion-weighted MRI and tumor control probability\u2014an in-silico study"],"prefix":"10.1093","volume":"96","author":[{"given":"Yaru","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kosmin","sequence":"additional","affiliation":[{"name":"Neuro-Oncology Team, Department of Oncology, University College London Hospital NHS Foundation Trust, 250 Euston Road, London, United Kingdom"},{"name":"National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuangling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shenzhen People's Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonian","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shenzhen People's Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shenzhen People's Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shenzhen People's Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Royle","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros","family":"Manolopoulos","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London, United Kingdom"},{"name":"Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Carlise, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou348"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-015-1716-2"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.6968"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-016-2347-y"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717X-9-130"},{"key":"b7","doi-asserted-by":"crossref","DOI":"10.1038\/srep42148","volume":"7","author":"Choi SH","year":"2017","journal-title":"Sci Rep"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.10.052"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20469-6"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(97)00911-5"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1999.91.2.0251"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)00467-3"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2006.12.070"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2011.06.020"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.04.002"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.04.018"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2017.1415457"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.08.013"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-011-0060-5"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2073"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717X-8-1"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5317-x"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20180901"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1038\/nature04960"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.1829"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007672"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2007.07.2062"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2010.11.005"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22068"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1148\/123.2.463"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/30604050"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1179\/174313209X382539"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1080\/02841850801918555"},{"key":"b35","first-page":"1419","volume":"27","author":"Hayashida Y","year":"2006","journal-title":"AJNR Am J Neuroradiol"},{"key":"b36","first-page":"309","volume":"27","author":"Chen J","year":"2005","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2241010637"},{"key":"b38","first-page":"1081","volume":"22","author":"Kono K","year":"2001","journal-title":"AJNR Am J Neuroradiol"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.177.2.1770449"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006431120031"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2586(199901)9:1<53::AID-JMRI7>3.0.CO;2-2"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160250"},{"key":"b43","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.10.151"},{"key":"b44","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12102858"},{"key":"b45","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-014-0638-9"},{"key":"b47","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-014-1485-3"},{"key":"b48","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.09090663"},{"key":"b49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191341"},{"key":"b50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162565"},{"key":"b51","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2010.10.001"},{"key":"b52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.09.040"},{"key":"b53","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(91)90171-Y"},{"key":"b54","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2010.498440"},{"key":"b55","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)01737-7"},{"key":"b56","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.09.007"},{"key":"b57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmp.2016.11.106"},{"key":"b58","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(95)00544-9"},{"key":"b59","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-8140(21)06866-3"},{"key":"b60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.05.001"},{"key":"b61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.12.011"},{"key":"b62","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"b63","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-020-01042-6"},{"key":"b64","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab040"},{"key":"b65","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa182"}],"container-title":["The British Journal of Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.birpublications.org\/doi\/pdf\/10.1259\/bjr.20220384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T16:44:51Z","timestamp":1705077891000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjr\/article\/7451307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":63,"journal-issue":{"issue":"1146","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1259\/bjr.20220384"],"URL":"https:\/\/doi.org\/10.1259\/bjr.20220384","relation":{},"ISSN":["0007-1285","1748-880X"],"issn-type":[{"value":"0007-1285","type":"print"},{"value":"1748-880X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]},"article-number":"20220384"}}