Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MRI.
OBJECTIVE
To investigate prospectively the potential of O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment.


METHODS
Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic (18)F-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 (18)F-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, (18)F-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.


RESULTS
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, (18)F-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by (18)F-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 (18)F-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 (18)F-FET uptake followed by a constant descent was more frequently observed in the nonresponders (P = 0.018).


CONCLUSIONS
Both standard and kinetic imaging parameters derived from(18)F-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.
Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Jülich, Jülich, Germany. Norbert.Galldiks@uk-koeln.de
Norbert
N
Galldiks
Marion
M
Rapp
Gabriele
G
Stoffels
Gereon R
GR
Fink
Nadim J
NJ
Shah
Heinz H
HH
Coenen
Michael
M
Sabel
Karl-Josef
KJ
Langen
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D000068258:Bevacizumab; D014443:Tyrosine