Flare Phenomenon in O-(2-¹⁸F-Fluoroethyl)-l-Tyrosine PET After Resection of Gliomas

Abstract

Purpose: PET using O-(2-[ 18 F]Fluoroethyl)-L-tyrosine (18 F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes of 18 F-FET uptake at the rim of the resection cavity within the first two weeks after resection of gliomas. In the present study, we evaluated pre-and postoperative 18 F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Methods: Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery, median 23 d, range 6-44 d) and postoperative 18 F-FET-PET (time after surgery, median 14, range 5-28 d) were included. PET scans (20-40 min p.i.) were evaluated visually for complete or incomplete resection (CR, IR) and compared with MRI. Changes of 18 F-FET-uptake in residual tumor were evaluated by tumorto-brain ratios (TBRmax) and in the vicinity of the resection cavity by maximum lesion-to-brain ratios (LBRmax). Results: Visual analysis of 18 F-FET PET scans revealed CR in 16/43 patients and IR in the remaining patients. PET results were concordant with MRI in 69% of the patients. LBRmax of 18 F-FET uptake in the vicinity of the resection cavity was significantly higher compared with preoperative values (1.59 ± 0.36 versus 1.14 ± 0.17; n=43, p<0.001). In 11 patients (26%) a "flare phenomenon" was observed with a considerable increase of 18 F-FET uptake compared with preoperative values in either the residual tumor (n=5) or in areas remote from tumor in the preoperative PET scan (n=6) (2.92 ± 1.24 versus 1.62 ± 0.75; p<0.001). Further follow-up in five patients showed decreasing 18 F-FET uptake in the flare areas in four and progress in one case.

Prognostic Potential of Postoperative 18F-Fluorocholine PET/CT in Patients With High-Grade Glioma. Clinical Validation of FuMeGA Postoperative PET Criteria

“…Concordances between PET and postoperative MRI have been reported in 56% to 81% of patients. 7,9,21,22 In agreement with previous reports, we found low concordance between both of them, with more PET-positive cases after surgery as compared with MRI-positive (Table 2). To prevent tumor regrowth, which could limit effective comparison between imaging techniques, the time interval between postoperative MRI and PET/CT should be shorter than 1 month, preferably less than 2 weeks.…”

“…Previous authors only reported incomplete resection when pathologic radiotracer uptake was present after surgery, without defining the specific postoperative pattern of radiotracer uptake. 21,22 In a preliminary assessment of our data set, we observed different uptake patterns around the resection cavity. Being cautious, no conclusive affirmations were done regarding its correspondence (tumor remnant vs inflammatory postoperative changes).…”

Worse prognosis for IDH wild-type diffuse gliomas with larger residual biological tumor burden

“…To mitigate this problem, two neuroradiologists validated the resected regions-of-interest (ROIs) by consensus using all available images. Alternatively, we calculated all imaging metrics from pre-operative images; thus, the strength of our method lies in the fact that imaging metrics do not suffer from post-surgical effects, such as blood-brain barrier breakdown or a postoperative are phenomenon, which may incur additional contrast enhancement or amino acid tracer uptake 19 . Second, due to the retrospective nature of the study, the parameters of MRI sequences and the term between PET examination and surgery or between surgery and post-operative imaging examination were not consistent.…”

18F-FET-PET-guided gross total resection improves overall survival in patients with WHO grade III/IV glioma: moving towards a multimodal imaging-guided resection

“…This lack of postoperative PET images is certainly an important limitation, however, there is still a significant scientific uncertainty at which time after surgery FET-PET shows residual tumor rather than reactive postoperative changes [24,51,52]. Furthermore, a recent study reported on a postoperative flare phenomenon with increased FET uptake the cause of which is not yet clear [23].…”

“…Molecular imaging using FET-PET can delineate the socalled biological tumor volume (BTV) [19,20] and identify the most active (and most malignant) tumor parts [21,22]. The potential of FET-PET to determine the extent of glioma resection has been investigated in several studies, and demonstrated additional information compared with conventional MRI [16,23,24]. A recent study in a larger series of patients with newly diagnosed glioblastoma demonstrated that preoperative BTV in FET-PET was larger than CE volume in MRI in 86% of the patients and in 10% of the patients increased FET uptake was present even outside areas of FLAIR hyperintensity [25].…”