{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:17:30Z","timestamp":1790626650754,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background\/objectives<\/jats:title><jats:p><jats:sup>18<\/jats:sup>F-DOPA is an amino acid radiotracer with high uptake in glioblastoma and low uptake in normal brain. Patients underwent pre-radiation and post-radiation <jats:sup>18<\/jats:sup>F-DOPA PET scans on a prospective clinical trial. This analysis investigates quantitative image features correlated with prognosis and treatment response to identify patients who benefit the most from dose-escalated therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quantitative image features from <jats:sup>18<\/jats:sup>F-DOPA PET scans of 58 glioblastoma patients were extracted from the high uptake region (TBR&amp;gt;2.0) in both pre-RT and early post-RT follow-up PET images, which were then refined using Pearson pair correlation. To explore the possibility to identify patients who benefit the most from dose-escalated therapy, pre-irradiation features were identified with univariate Cox regression analysis. Classifications with simple threshold or with Decision Tree models were carried out to categorize patients into distinct survival groups. Additionally, the features with notable changes before and after RT were identified and the temporal patterns of these changes between the survival groups were compared. Multivariates cox analysis was performed to assess the prognostic value of delta features in survival analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The pre-irradiation features demonstrated predictive capability in distinguishing survival groups, yielding an accuracy of 0.78 on the reserved test dataset. We also pinpointed eight quantitative features that exhibited a significant difference before and after radiotherapy in patients with MGMT-unmethylated glioblastoma. The change of the features presented different patterns between the survival groups separated by median overall survival and the inclusion of delta features can enhance the accuracy of survival analysis. Conversely, for patients with methylated MGMT, no feature displayed such significant changes between preRT and early postRT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study showcased the potential of employing quantitative features derived from <jats:sup>18<\/jats:sup>F-DOPA images to refine the stratification of patients with unmethylated MGMT for dose escalated therapy. Moreover, the change of these features can serve as valuable tools for monitoring treatment responses following radiotherapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1623313","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T06:35:05Z","timestamp":1755066905000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of imaging signatures in 18F-DOPA PET of glioblastoma treated with dose-escalated radiotherapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna H.","family":"Pafundi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Breen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek R.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Kemp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sani H.","family":"Kizilbash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J.","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Ruff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jann N.","family":"Sarkaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon H.","family":"Uhm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Zakhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maasa H.","family":"Seaberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hok Seum","family":"Wan Chan Tseung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia N.","family":"Laack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra H.","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1001\/jamaoncol.2017.5082","article-title":"Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: A secondary analysis of a randomized clinical trial","volume":"4","author":"Taphoorn","year":"2018","journal-title":"JAMA Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.810263","article-title":"High-grade glioma treatment response monitoring biomarkers: A position statement on the evidence supporting the use of advanced MRI techniques in the clinic, and the latest bench-to-bedside developments. 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