O-(2-18F-Fluoroethyl)-L-Tyrosine PET Predicts Failure of Antiangiogenic Treatment in Patients with Recurrent High-Grade Glioma (original) (raw)
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Journal of Nuclear Medicine, 2012
With the dismal prognosis for malignant glioma patients, survival predictions become key elements in patient management. This study compares the value of 3′-deoxy-3′-18 Ffluorothymidine (18 F-FLT) PET and MRI for early outcome predictions in patients with recurrent malignant glioma on bevacizumab therapy. Methods-Thirty patients treated with bevacizumab combination therapy underwent 18 F-FLT PET immediately before and at 2 and 6 wk after the start of treatment. A metabolic treatment response was defined as a decrease of equal to or greater than 25% in tumor 18 F-FLT uptake (standardized uptake values) from baseline using receiver-operating-characteristic analysis. MRI treatment response was assessed at 6 wk according to the Response Assessment in Neurooncology criteria. 18 F-FLT responses at different times were compared with MRI response and correlated with progression-free survival and overall survival using Kaplan-Meier analysis. Metabolic response based on 18 F-FLT was further compared with other outcome predictors using Cox regression analysis. Results-Early and late changes in tumor 18 F-FLT uptake were more predictive of overall survival than MRI criteria (P < 0.001 and P = 0.01, respectively). 18 F-FLT uptake changes were also predictive of progression-free survival (P < 0.001). The median overall survival for responders was 3.3 times longer than for nonresponders based on 18 F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk 18 F-FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%), whereas MRI identified 9 responders (7 partial response, 2 complete response, 31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7 of the 8 discrepant cases between MRI and PET, 18 F-FLT PET was able to demonstrate response earlier
Frontiers in Oncology, 2021
BackgroundMRI-based differential diagnosis of glioma recurrence (GR) and treatment-induced changes (TICs) remain elusive in up to 30% of treated glioma patients. We aimed to determine 18F-FET PET diagnostic performance in this clinical scenario, its outcome dependency on established prognostic factors, optimal 18F-FET semi-quantitative thresholds, and whether 18F-FET parameters may instantly predict progression-free survival (PFS) and overall survival (OS).MethodsWe retrospectively analyzed 45 glioma patients treated with chemoradiation therapy (32 males; mean age: 51 years, glioma grade: n=26 WHO4; n=15 WHO3; n=4 WHO2) who underwent 18F-FET PET to resolve differential diagnosis of GR and TICs raised by MRI performed in the preceding 2 weeks and depicting any of the following changes in their radiation field: volumetric increase of contrast-enhancing lesions; new contrast-enhancing lesion; significant increase in T2/FLAIR non-enhancing lesion without reducing corticosteroids. 18F-FE...
Journal of Nuclear Medicine, 2013
In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-18 F-fluoroethyl)-L-tyrosine (18 F-FET) PET to noninvasively detect malignant progression in patients with LGG. Methods: Twenty-seven patients (mean age 6 SD, 44 6 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic 18 F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBR max and TBR mean , respectively) of 18 F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 • 2 contingency tables. Results: In patients with histologically proven malignant progression toward WHO grade III or IV (n 5 18), TBR max and TBR mean increased significantly, compared with baseline (TBR max , 3.8 6 1.0 vs. 2.4 6 1.0; TBR mean , 2.2 6 0.3 vs. 1.6 6 0.6; both P , 0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P , 0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P , 0.001). The combined analysis of 18 F-FET PET parameters (i.e., changes of TBR max, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P 5 0.003). Conclusion: Both tumor-to-brain ratio and kinetic parameters of 18 F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated 18 F-FET PET may be helpful for further treatment decisions.
2023
Purpose: To explore a prognostic or predictive role of MRI and O-(2-18 F-fluoroethyl)-L-tyrosine (18 FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18 FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm 3 0.94; 95% confidence interval (CI), 0.89-0.99] and for higher ADC (HR 0.18; CI, 0.05-0.66). Higher 18 FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P ¼ 0.09). High 18 FET-TBR of noncontrastenhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16-30.8). Conclusions: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18 FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.
Journal of Nuclear Medicine, 2013
To date, the use of structural MR imaging (including contrast-enhanced and T2-weighted or fluid-attenuated inversion recovery-weighted images) is the standard method to diagnose tumor progression and to assess antiangiogenic treatment effects. However, several studies have suggested that O-(2-18 F-fluoroethyl)-L-tyrosine (18 F-FET) PET adds valuable clinical information to the information derived from structural MR imaging alone. We evaluated the effectiveness and cost-effectiveness of the addition of 18 F-FET PET to structural MR imaging for the management of treatment with bevacizumab and irinotecan (BEV/IR) in patients with recurrent high-grade glioma compared with MR imaging alone from the perspective of the German Statutory Health Insurance. Methods: To evaluate the incremental cost-effectiveness of the additional use of 18 F-FET PET, a decision tree model was used. Effectiveness of 18 F-FET PET was defined as correct identification of both tumor progression before BEV/IR treatment initiation and BEV/IR treatment response and was evaluated for the combination of 18 F-FET PET and MR imaging compared with MR imaging alone. Costs were estimated for a baseline scenario and for a more expensive scenario. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. Results: The use of 18 F-FET PET resulted in a number needed to diagnose of 2.4, that is, 3 additional patients have to be diagnosed to avoid 1 wrong diagnosis. The incremental costeffectiveness ratio of 18 F-FET PET/MR imaging compared with MR imaging alone was V5,725 (V1 $1.30) for the baseline scenario and V8,145 for the more expensive scenario per additional correct diagnosis. The probabilistic sensitivity analysis confirmed the robustness of the results. Conclusion: The model suggests that the additional use of 18 F-FET PET in the management of patients with recurrent high-grade glioma treated with BEV/IR may be cost-effective. Integration of 18 F-FET PET has the potential to avoid overtreatment and corresponding costs, as well as unnecessary side effects to the patient.
AJR. American journal of roentgenology, 2018
In MRI of patients with recurrent glioblastoma, bevacizumab-induced normalization of tumor vascularity can be difficult to differentiate from antitumor effects. The aim of this study was to assess the utility of F-fluoroethyl-L-tyrosine (FET) PET in the evaluation of recurrent glioblastoma treated with bevacizumab. MRI and FET PET were performed before and after administration of two doses of bevacizumab to 11 patients with recurrent glioblastoma. The ratio between normalized FET uptake at follow-up and baseline of the entire (volume of T2 FLAIR abnormality) and enhancing tumor were assessed for prediction of progression-free survival (PFS) and overall survival (OS). Voxel-wise Spearman correlation between normalized FET uptake and contrast-enhanced T1 signal intensity was assessed and tested as a predictor of PFS and OS. Mean Spearman correlation between FET uptake and contrast-enhanced T1 signal intensity before therapy was 0.65 and after therapy was 0.61 (p = 0.256). The median P...
Diagnostic of FET PET in Patients with Recurrent Glioma: Case Series
Journal of Nuclear Medicine & Radiation Therapy
Background: The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [ 18 F]O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ([ 18 F]FET). Methods: Four patients with the suspicion of high and low-grade were enrolled. Patients underwent postoperative [ 18 F] FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. Results: In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [ 18 F]FET-PET revealeda legion of increased radiotracer uptake in the dura in the carniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, There was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUV max =3.79, so the study was negative for recurrence evaluation. In patient 3 therewas no abnormal uptake withnegative result for recurrence of brain tumor.Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Conclusion: Assessment of the resection legions in high and low-grade gliomas with [ 18 F] FET-PET seems to be useful. Labelled amino acid tracers may predict the response to the chemo-radiotherapy and early detection of residual tumor after surgery.
PloS one, 2016
Bevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage. We reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application. After BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2017
To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria. Fifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PETvol and the composite MRPETvol, respectively. MGMT-methylation (p=0.03), larger PETvol (p<0.001), and less extensive surgery (p<0.001), were associated with larger PETvol ov...