Assessment of Treatment Response in Patients with Glioblastoma Using O-(2-¹⁸F-Fluoroethyl)-l-Tyrosine PET in Comparison to MRI

Abstract

The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET PET) during treatment. Methods: In a prospective study, 25 patients with glioblastoma were investigated by MRI and 18 F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR max and TBR mean , respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrastenhancement volumes on MRI (Gd-volume) and tumor volumes in 18 F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T vol 1.6 ) were calculated using threshold-based volume-ofinterest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses. Results: Early after completion of RCX, a decrease of both TBR max and TBR mean was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR max between FET-1 and FET-2 of more than 20% predicted poor survival, with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR max and TBR mean was less significant, but an association between a decrease of T vol 1.6 and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival. Conclusion: In contrast to Gd-volumes on MRI, changes in 18 F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.

Letter to the Editor: “The role of imaging in the management of progressive glioblastoma. A systematic review and evidence-based clinical practice guideline” [J Neurooncol 2014; 118:435–460]

“…Furthermore, a prospective study evaluated the prognostic value of early changes of FET uptake after postoperative radiochemotherapy in patients with glioblastoma [7,8]. PET responders with a decrease of the tumor/brain ratio of more than 10% had a significantly longer disease-free survival and overall survival than patients with stable or increasing tracer uptake after RCx.…”

“…PET responders with a decrease of the tumor/brain ratio of more than 10% had a significantly longer disease-free survival and overall survival than patients with stable or increasing tracer uptake after RCx. Additionally, a reliable treatment monitoring was also demonstrated in various experimental approaches (e.g., radioimmunotherapy, convection enhanced delivery of paclitaxel) and for antiangiogenic treatment with bevacizumab and irinotecan [7][8][9][10][11][12].…”

Novel Quantitative Techniques in Hybrid (PET-MR) Imaging of Brain Tumors

“…This study and other studies have exemplified the relevance of metabolically active tumor volumes in AA-PET to assess treatment response. 59,60 Fig. 7 demonstrates a typical case in which PET plays an important role in delineating biologically active tumor volume over MR alone.…”

PET for Therapy Response Assessment in Glioblastoma

“…Treatment response and outcome in bevacizumab therapy has been suggested to be better assessed by 18 F-FET and 18 F-FDOPA, compared to MRI (6,(74)(75)(76)(77). Also, reliable monitoring of TMZ and nitrosourea-based chemotherapy effects has been demonstrated in patients with recurrent HGG (9,31,64,66,70,71). In a study by Rachinger et al, 18 F-FET PET was able to distinguish tumor progression from stable disease with 93% specificity and 100% sensitivity, while the specificity of conventional MRI alone was 50% (78).…”

“…Current amino acid PET data suggest that deactivation of amino acid transport and/or decrease of the metabolically active tumor volume is a sign of treatment response associated with long-term outcome (6,(70)(71)(72)(73). Treatment response and outcome in bevacizumab therapy has been suggested to be better assessed by 18 F-FET and 18 F-FDOPA, compared to MRI (6,(74)(75)(76)(77).…”