Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-l-tyrosine PET in comparison to MRI
To investigate prospectively the potential of O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment.
Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic 18F-FET PET scans were obtained at baseline and at follow-up after the start of treatment (median 4.9 weeks). Using MRI treatment response was evaluated according to RANO (Response Assessment in Neuro-Oncology) criteria. For 18F-FET PET evaluation, a reduction >45 % of the metabolically active tumour volume was considered as a treatment response, with the metabolically active tumour being defined as a tumour-to-brain ratio (TBR) of ≥1.6. The results of the treatment assessments were related to progression-free survival (PFS) and overall survival (OS). For further evaluation of PET data, maximum and mean TBR were calculated using region-of-interest analysis at baseline and at follow-up. Additionally, 18F-FET uptake kinetic studies were performed at baseline and at follow-up in all patients. Time–activity curves were generated and the times to peak (TTP) uptake (in minutes from the beginning of the dynamic acquisition to the maximum uptake) were calculated.
At follow-up, MRI showed a complete response according to RANO criteria in one of the ten patients (10 %), a partial response in five patients (50 %), and stable disease in four patients (40 %). Thus, MRI did not detect tumour progression. In contrast, 18F-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by 18F-FET PET predicted a significantly longer PFS (median PFS, 9 vs. 3 months; P = 0.001) and OS (median OS 23.0 months vs. 3.5 months; P = 0.001). Furthermore, in four patients (40 %), diagnosis according to RANO criteria and by 18F-FET PET was discordant. In these patients, PET was able to detect tumour progression earlier than MRI (median time benefit 10.5 weeks; range 6–12 weeks). At baseline and at follow-up, in nonresponders TTP was significantly shorter than in responders (baseline TTP 10 ± 8 min vs. 35 ± 9 min; P = 0.002; follow-up TTP 23 ± 9 min vs. 39 ± 8 min; P = 0.02). Additionally, at baseline a kinetic pattern characterized by an early peak of 18F-FET uptake followed by a constant descent was more frequently observed in the nonresponders (P = 0.018).
Both standard and kinetic imaging parameters derived from18F-FET PET seem to predict BEV/IR treatment failure and thus contribute important additional information for clinical management over and above the information obtained by MRI response assessment based on RANO criteria.
KeywordsKinetic analysis RANO criteria Anti-VEGF treatment Amino acid PET Metabolic response
The authors wish to thank Suzanne Schaden, Elisabeth Theelen and Kornelia Frey for assistance in the patient studies and Dr. Johannes Ermert, Silke Grafmüller, Erika Wabbals and Sascha Rehbein for radiosynthesis of 18F-FET. The Brain Imaging Center West (BICW) supported this work.
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