{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:31:44Z","timestamp":1772609504358,"version":"3.50.1"},"reference-count":18,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The aim of this study was to establish the relationship between target size and the required diagnostic PET maximum standard uptake value (SUVmax) thresholds needed for successful Biology-guided Radiotherapy (BgRT) delivery on RefleXion X1 PET-linac. The current clinical eligibility recommendation is an SUVmax \u2265 6 at simulation, but the RefleXion system subsequently evaluates Activity Concentration (AC), which must exceed 5 kBq\/mL for successful BgRT planning. Methods: A custom 3D-printed phantom containing six spherical targets (8 to 20 mm diameter) was used with varying target-to-background ratios (5:1 to 20:1) of 18F-FDG to systematically achieve a range of SUVmax values for each target size. Images were acquired on Siemens Biograph mCT for SUVmax quantification and RefleXion X1 for AC measurements. Twenty-four BgRT plans were evaluated, and delivery accuracy was validated using ArcCHECK. Additionally, retrospective data from 18 patients across four institutions were analyzed to validate the phantom-derived findings. Results: The PET-linac successfully planned treatments for 13\/24 experiments, all achieving an AC &gt; 5 kBq\/mL. SUVmax requirements varied by target size: 16\u201320 mm targets required an SUVmax &gt; 6, consistent with current recommendations, while smaller targets required higher thresholds (e.g., 13 mm: SUVmax &gt; 10, and 11 mm: SUVmax &gt; 15). 8 and 9 mm targets failed to meet AC requirements even at SUVmax 14. Successful deliveries maintained acceptable accuracy, with gamma passing rates of 92.4% \u00b1 5.0% (3%\/2 mm) and 97.6% \u00b1 1.9% (3%\/3 mm). Analysis revealed that Volume (cc) \u00d7 SUVmax &gt; 11 consistently predicted successful BgRT planning across all target sizes. This threshold was validated using multi-institutional PET-CT patient data (mean: 11.36, 95% CI: 9.1\u201312.9), correctly predicting treatment eligibility in 15 of 18 cases. Conclusions: Target size significantly influences BgRT eligibility. We derived a new criterion, Volume(cc) \u00d7 SUVmax &gt; 11 (95% CI: 9.1\u201312).<\/jats:p>","DOI":"10.3390\/cancers17223645","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"3645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-Institutional Verification of a Novel Predictor (Volume-Scaled SUVmax) for Successful Biology-Guided Radiotherapy Delivery of Small Targets"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-7359","authenticated-orcid":false,"given":"M. Ramish","family":"Ashraf","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish","family":"Bal","sequence":"additional","affiliation":[{"name":"RefleXion Medical, Hayward, CA 94545, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huixiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9366-8514","authenticated-orcid":false,"given":"Henry S.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Medical Center, Duarte, CA 91010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahed N.","family":"Badiyan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas K.","family":"Vitzthum","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-0544","authenticated-orcid":false,"suffix":"Jr.","given":"Billy W.","family":"Loo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1693-6850","authenticated-orcid":false,"given":"Murat","family":"Surucu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13638","DOI":"10.1002\/acm2.13638","article-title":"Treatment planning system commissioning of the first clinical biology-guided radiotherapy machine","volume":"23","author":"Simiele","year":"2022","journal-title":"J. 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