The diagnostic accuracy of detecting malignant transformation of low-grade glioma using O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography: a retrospective study

Abstract

Objective: The diagnostic accuracy of O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the diagnostic potential of FET PET in patients with MRI-suspected malignant progression of LGGs that had previously been treated and the relationship between FET uptake and MRI and molecular biomarkers.

Methods: Forty-two patients who had previously undergone surgical or multimodal treatment for a histologically verified LGG were referred for FET PET assessment because of clinical signs and/or MRI findings suggestive of tumor progression. Maximal and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively) on FET PET as well as kinetic FET PET parameters (time to peak [TTP] and time-activity curve [TAC]) were determined. Final diagnoses were confirmed histologically. The diagnostic accuracy of FET parameters, separately and combined, for the detection of malignant progression was evaluated using receiver operating characteristic (ROC) curve analysis. Possible predictors that might influence the diagnostic accuracy of FET PET were assessed using multiple linear regression analysis. Spearman’s rank correlation r method was applied to determine the correlation between TBRmax and TAC, and molecular biomarkers from tumor tissues.

Results: A total of 47 FET PET scans were obtained and showed no significant association between FET parameters and contrast enhancement on MRI. ROC curve analyses overall were unable to demonstrate any significant differentiation between nontransformed LGGs and LGGs that had transformed to high-grade gliomas when evaluating FET parameters separately or combined. After excluding the oligodendroglial subgroup, a significant difference was observed between nontransformed and transformed LGGs when combining FET parameters (i.e., TBRmax > 1.6, TAC describing a plateau or decreasing pattern, and TTP < 25 minutes), with the best result yielded by a combined analysis of TBRmax > 1.6 and TAC with a plateau or decreasing pattern (sensitivity 75% and specificity 83%, p = 0.003). The difference was even greater when patients who had previously undergone oncological treatment were also excluded (sensitivity 93% and specificity 100%, p = 0.001). Multiple linear regression analysis revealed that the presence of an oligodendroglial component (p = 0.029), previous oncological treatment (p = 0.039), and the combined FET parameters (p = 0.027) were significant confounding factors in the detection of malignant progression. TBRmax was positively correlated with increasing cell density (p = 0.040) and inversely correlated with IDH1 mutation (p = 0.006).

Conclusions: A single FET PET scan obtained at the time of radiological and/or clinical progression seems to be of limited value in distinguishing transformed from nontransformed LGGs, especially if knowledge of the primary tumor histopathology is not known. Therefore, FET PET imaging alone is not adequate to replace histological confirmation, but it may provide valuable information on the location and delineation of active tumor tissue, as well as an assessment of tumor biology in a subgroup of LGGs.

Keywords: 18F-FET PET; AUC = area under the curve; FDOPA = 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine; FET = O-(2-[18F]fluoroethyl)-l-tyrosine; FET10–30 = 10- to 30-minute FET; FET20–40 = 20- to 40-minute FET; HGG = high-grade glioma; IQR = interquartile range; LGG = low-grade glioma; MET = 11C-methionine; PFS = progression-free survival; RANO = Response Assessment in Neuro-Oncology; ROC = receiver operating characteristic; ROI = region of interest; SUV = standardized uptake value; TAC = time-activity curve; TBRmax = maximal tumor-to-brain ratio; TBRmean = mean tumor-to-brain ratio; TTM = time to malignant transformation; TTP = time to peak; low-grade glioma; malignant transformation; oncology.