{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:04:08Z","timestamp":1787313848949,"version":"build-2736575974"},"reference-count":15,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RefleXion Medical"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: This study aims to present a structured clinical workflow for offline adaptive Biology-guided Radiotherapy (BgRT) using the RefleXion X1 PET-linac system, addressing challenges introduced by inter-treatment anatomical and biological changes. Methods: We propose a decision tree offline adaptation framework based on real-time assessments of Activity Concentration (AC), Normalized Target Signal (NTS), and bounded dose-volume histogram (bDVH%) metrics. Three offline strategies were developed: (1) preemptive adaptation for minor changes, (2) partial re-simulation for moderate changes, and (3) full re-simulation for major anatomical or metabolic alterations. Two clinical cases demonstrating strategies 1 and 2 are presented. Results: The preemptive adaptation strategy was applied in a case with early tumor shrinkage, maintaining delivery parameters within acceptable limits while updating contours and dose distribution. In the partial re-Simulation case, significant changes in PET signal necessitated a same-day PET functional modeling session and plan re-optimization, effectively restoring safe deliverability. Both cases showed reduced target volumes and improved OAR sparing without additional patient visits or tracer injections. Conclusions: Offline adaptive workflows for BgRT provide practical solutions to address inter-fractional changes in tumor structure and function. These strategies can help maintain the safety and accuracy of BgRT delivery and support clinical adoption of PET-guided radiotherapy, paving the way for future online adaptive capabilities.<\/jats:p>","DOI":"10.3390\/cancers17152470","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T16:06:17Z","timestamp":1753459577000},"page":"2470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Strategies for Offline Adaptive Biology-Guided Radiotherapy (BgRT) on a PET-Linac Platform"],"prefix":"10.3390","volume":"17","author":[{"given":"Bin","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas I.","family":"Banks","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rameshwar","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Bal","sequence":"additional","affiliation":[{"name":"RefleXion Medical, Hayward, CA 94545, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Godley","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Pompos","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Garant","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-5923","authenticated-orcid":false,"given":"Kenneth","family":"Westover","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, 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Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101212","DOI":"10.1016\/j.adro.2023.101212","article-title":"Positron Emission Tomography (PET)\/Computed Tomography (CT) Imaging in Radiation Therapy Treatment Planning: A Review of PET Imaging Tracers and Methods to Incorporate PET\/CT","volume":"8","author":"Trotter","year":"2023","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.soc.2023.02.006","article-title":"Biology-guided radiation therapy: An evolving treatment paradigm","volume":"32","author":"Ladbury","year":"2023","journal-title":"Surg. Oncol. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrclinonc.2010.218","article-title":"PET\u2013CT for radiotherapy treatment planning and response monitoring in solid tumors","volume":"8","author":"Bussink","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1053\/j.semnuclmed.2012.04.003","article-title":"The Role of Positron Emission Tomography\/Computed Tomography in Radiation Therapy Planning for Patients with Lung Cancer","volume":"42","author":"Hicks","year":"2012","journal-title":"Semin. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20160764","DOI":"10.1259\/bjr.20160764","article-title":"Radiotherapy response evaluation using FDG PET-CT\u2014Established and emerging applications","volume":"90","author":"Cliffe","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dejanovic, D., Specht, L., Czyzewska, D., Berthelsen, A.K., and Loft, A. (2022). Response Evaluation Following Radiation Therapy With (18)F-FDG PET\/CT: Common Variants of Radiation-Induced Changes and Potential Pitfalls. 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Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20220387","DOI":"10.1259\/bjr.20220387","article-title":"Image-mode performance characterisation of a positron emission tomography subsystem designed for Biology-guided radiotherapy (BgRT)","volume":"96","author":"Hu","year":"2022","journal-title":"Br. J. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100438","DOI":"10.1016\/j.phro.2023.100438","article-title":"Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform","volume":"26","author":"Zhuang","year":"2023","journal-title":"Phys. Imaging Radiat. 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