Serial 18F-FET PET imaging of primarily 18F-FET-negative glioma: Does it make sense?

Abstract

PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has gained increasing importance for glioma management. With regard to the occurrence of 18F-FET-negative glioma, we investigated the value of 18F-FET PET monitoring of primarily 18F-FET-negative gliomas concerning the detection of progression and malignant transformation. Methods: We included 31 patients (26 World Health Organization [WHO] grade II, 5 WHO grade III) with primarily 18F-FET-negative glioma and available 18F-FET PET follow-up. 18F-FET PET analysis comprised maximal tumor-to-background ratio (TBRmax) and dynamic analysis of tumoral 18F-FET uptake over time (increasing vs. decreasing) including minimal time to peak (TTPmin). PET findings were correlated with MRI and clinical findings of progression as well as histology of recurrent tumors. Results: Twenty-three of 31 patients experienced tumor progression (median progression-free survival, 41.7 mo). Fourteen of 23 patients showed tumoral 18F-FET uptake concurrent to and 4 of 23 before MRI-derived or clinical signs of tumor progression; 2 of 23 patients presented signs of progression in MRI when no concomitant 18F-FET PET was available, but subsequent follow-up PET was positive. In 3 of 23 patients, no 18F-FET uptake was detected at tumor progression. Overall, 20 of 31 primarily 18F-FET-negative glioma turned 18F-FET-positive during the followup. At first occurrence of tumoral 18F-FET uptake, TBRmax was significantly higher in patients with malignant transformation (11/20) than in those without malignant progression (3.2 ± 0.9 vs. 1.9 ± 0.5; P 5 0.001), resulting in a high detection rate for malignant transformation (for TBRmax. 2.46: sensitivity, 82%; specificity, 89%; negative predictive value, 80%; positive predictive value, 90%; and accuracy, 85%). Although static evaluation was superior to dynamic analysis for the detection of malignant transformation (for TTPmin # 17.5 min: sensitivity, 73%; specificity, 67%; negative predictive value, 67%; positive predictive value, 73%; and accuracy, 70%), short TTPmin was associated with an early malignant transformation in the further disease course. Overall, 18 of 31 patients experienced malignant transformation; of these, 16 of 17 (94%) evaluable patients showed 18F-FET uptake at the time of malignant transformation. Conclusion: 18F-FET PET monitoring with static and dynamic evaluation is useful even in primarily 18F-FET-negative glioma, providing a high detection rate of both tumor progression and malignant transformation, partly before further signs of progression in MRI. Hence, 18F-FET uptake indicating malignant transformation might influence the patient management.