The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET PET) during treatment. Methods: In a prospective study, 25 patients with glioblastoma were investigated by MRI and 18 F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR max and TBR mean , respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrastenhancement volumes on MRI (Gd-volume) and tumor volumes in 18 F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T vol 1.6 ) were calculated using threshold-based volume-ofinterest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses. Results: Early after completion of RCX, a decrease of both TBR max and TBR mean was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR max between FET-1 and FET-2 of more than 20% predicted poor survival, with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR max and TBR mean was less significant, but an association between a decrease of T vol 1.6 and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival. Conclusion: In contrast to Gd-volumes on MRI, changes in 18 F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.
The aim of this study was to investigate the potential of O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult. Methods: Thirty-one patients (mean age 6 SD, 53 6 11 y) with single or multiple contrastenhancing brain lesions (n 5 40) on MRI after radiation therapy of brain metastases were investigated with dynamic 18 F-FET PET. Maximum and mean tumor-to-brain ratios (TBR max and TBR mean , respectively; 20-40 min after injection) of 18 F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing 18 F-FET uptake, (II) 18 F-FET uptake peaking early (TTP # 20 min) followed by a plateau, and (III) 18 F-FET uptake peaking early (TTP # 20 min) followed by a constant descent. The diagnostic accuracy of the TBR max and TBR mean of 18 F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 · 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference. Results: Both TBR max and TBR mean were significantly higher in patients with recurrent metastasis (n 5 19) than in patients with radiation necrosis (n 5 21) (TBR max , 3.2 6 0.9 vs. 2.3 6 0.5, P , 0.001; TBR mean , 2.1 6 0.4 vs. 1.8 6 0.2, P , 0.001). The diagnostic accuracy of 18 F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR max (area under the ROC curve [AUC], 0.822 6 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P 5 0.001), 83% using TBR mean (AUC, 0.851 6 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P , 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P , 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR mean greater than 1.9 and curve pattern II or III were present (AUC, 0.959 6 0.03; sensitivity, 95%; specificity, 91%; P , 0.001). Conclusion: Our findings suggest that the combined evaluation of the TBR mean of 18 F-FET uptake and the pattern of the timeactivity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. 18 F-FET PET may thus contribute significantly to the management of patients with brain metastases. The improvement in the treatment of solid tumors has led to an increasing number of patients who experience brain metastases during the course of the disease. Stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) are commonly used to treat brain metastases, and a growing percentage of patients live long enough to experience a local relapse of these me...
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