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The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan–Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival. [ABSTRACT FROM AUTHOR]

The study performs a comprehensive analysis of image metrics to objectively support the reduction of injected activity in pediatric oncology 18F-FDG PET/MR (18F-fludeoxyglucose PET/MR) examinations. Contrast-to-Noise Ratio (CNR), Normalized Noise (NN), tumor burden, and standardized uptake value (SUV) parameters stability were investigated to robustly define the acceptable reduced activity level that preserves the clinical utility of images, considering different PET applications. 21 PET/MRI examinations performed on a 3-Tesla Biograph mMR scanner were analyzed. Tracer activity reduction was stimulated by decreasing the count statistics of the original list-mode data (3 MBq kg–1). In addition to the already studied SUV metrics and subjective scoring on lesion detectability, a thorough analysis of CNR, NN, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) was performed. SUVmax and SUVmean increased more than 5% only in 0.6 MBq kg–1 reconstructed images (+10% and +9%, respectively), while SUVpeak was almost unaffected (average variations < 2%). The quantified CNR, NN, MTV, and TLG behavior with the decrease of the injected activity clearly defines 1.5 MBq kg–1 as a threshold of activity after which the quality of the image degrades. Subjective and objective analyses yielded consistent results. All 56 lesions were detected until activity of 1.2 MBq kg–1, whereas five lesions were missed on the 0.6 MBq kg–1 image. Perceived image quality (IQ) decreased in Lower Tracer Activity (LTA) images but remained acceptable until 1.5 MBq kg–1. Results about the stability of image metrics beyond the semi-quantitative SUV parameters and subjective analysis, rigorously proves the feasibility of the reduction of injected activity to 1.5 MBqkg-1 for pediatric patients aged between 7 and 17 years. This is the first report on the quantitative evaluation of the effect of activity reduction on image quality in pediatric PET/MR. The findings offer objective corroboration to the feasibility of a significant dose reduction without consequences on clinical image reading and tumor burden metrics. [ABSTRACT FROM AUTHOR]

Objective: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2- 18 F-fluoroethyl)-L-tyrosine positron emission tomography ([ 18 F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [ 18 F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib., Methods: We retrospectively reviewed 16 consecutive GBM patients who underwent [ 18 F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [ 18 F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis., Results: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC ( R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects ( p = 0.0023). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria ( p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival., Conclusion: In recurrent glioblastoma patients treated with regorafenib, [ 18 F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment., Advances in Knowledge: Simultaneous evaluation of [ 18 F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.

Objective:: The study performs a comprehensive analysis of image metrics to objectively support the reduction of injected activity in pediatric oncology 18 F-FDG PET/MR ( 18 F-fludeoxyglucose PET/MR) examinations. Contrast-to-Noise Ratio (CNR), Normalized Noise (NN), tumor burden, and standardized uptake value (SUV) parameters stability were investigated to robustly define the acceptable reduced activity level that preserves the clinical utility of images, considering different PET applications., Methods:: 21 PET/MRI examinations performed on a 3-Tesla Biograph mMR scanner were analyzed. Tracer activity reduction was stimulated by decreasing the count statistics of the original list-mode data (3 MBq kg -1 ). In addition to the already studied SUV metrics and subjective scoring on lesion detectability, a thorough analysis of CNR, NN, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) was performed., Results:: SUVmax and SUVmean increased more than 5% only in 0.6 MBq kg -1 reconstructed images (+10% and +9%, respectively), while SUVpeak was almost unaffected (average variations < 2%). The quantified CNR, NN, MTV, and TLG behavior with the decrease of the injected activity clearly defines 1.5 MBq kg -1 as a threshold of activity after which the quality of the image degrades. Subjective and objective analyses yielded consistent results. All 56 lesions were detected until activity of 1.2 MBq kg -1 , whereas five lesions were missed on the 0.6 MBq kg -1 image. Perceived image quality (IQ) decreased in Lower Tracer Activity (LTA) images but remained acceptable until 1.5 MBq kg -1 ., Conclusion:: Results about the stability of image metrics beyond the semi-quantitative SUV parameters and subjective analysis, rigorously proves the feasibility of the reduction of injected activity to 1.5 MBqkg -1 for pediatric patients aged between 7 and 17 years., Advances in Knowledge:: This is the first report on the quantitative evaluation of the effect of activity reduction on image quality in pediatric PET/MR. The findings offer objective corroboration to the feasibility of a significant dose reduction without consequences on clinical image reading and tumor burden metrics.