AUTHOR=Qian Jing , Pafundi Deanna H. , Breen William G. , Brown Paul D. , Hunt Christopher H. , Jacobson Mark S. , Johnson Derek R. , Kaufmann Timothy J. , Kemp Bradley J. , Kizilbash Sani H. , Lowe Val J. , Ruff Michael W. , Sarkaria Jann N. , Uhm Joon H. , Zakhary Mark J. , Seaberg Maasa H. , Wan Chan Tseung Hok Seum , Yan Elizabeth S. , Zhang Yan , Laack Nadia N. , Brinkmann Debra H. TITLE=Analysis of imaging signatures in 18F-DOPA PET of glioblastoma treated with dose-escalated radiotherapy JOURNAL=Frontiers in Oncology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1623313 DOI=10.3389/fonc.2025.1623313 ISSN=2234-943X ABSTRACT=Background/objectives18F-DOPA is an amino acid radiotracer with high uptake in glioblastoma and low uptake in normal brain. Patients underwent pre-radiation and post-radiation 18F-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.MethodsQuantitative image features from 18F-DOPA PET scans of 58 glioblastoma patients were extracted from the high uptake region (TBR>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.ResultsThe 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.ConclusionsOur study showcased the potential of employing quantitative features derived from 18F-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.