Early treatment response assessment using <sup>18</sup>F-FET PET compared to contrast-enhanced MRI in glioma patients following adjuvant temozolomide chemotherapy
Garry Ceccon, Philipp Lohmann, Jan‐Michael Werner, Caroline Tscherpel, Veronika Dunkl, Gabriele Stoffels, Jurij Rosen, Marion Rapp, Michael Sabel, Ulrich Herrlinger, Niklas Schaefer, N. Jon Shah, Gereon R. Fink, Karl‐Josef Langen, Norbert Galldiks
Abstract
The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[<sup>18</sup>F]fluoroethyl)-l-tyrosine (<sup>18</sup>F-FET) PET for response assessment in glioma patients after adjuvant temozolomide chemotherapy (TMZ). <b>Methods:</b> After biopsy or resection and completion of radiotherapy with concomitant TMZ, 41 newly diagnosed and histomolecularly characterized glioma patients (glioblastoma, 90%; age range, 20–79 y) were subsequently treated with adjuvant TMZ. MR and <sup>18</sup>F-FET PET imaging were performed at baseline and after the second cycle of adjuvant TMZ. We obtained <sup>18</sup>F-FET metabolic tumor volumes (MTVs) as well as mean and maximum tumor-to-brain ratios (TBR<sub>mean</sub> and TBR<sub>max</sub>, respectively). Threshold values of <sup>18</sup>F-FET PET parameters to predict outcome were established by receiver-operating-characteristic analyses using a median progression-free survival (PFS) of ≥ 9 mo and overall survival (OS) of ≥ 15 mo as reference. MRI response assessment was based on the Response Assessment in Neuro-Oncology (RANO) working group criteria. The predictive value of changes of <sup>18</sup>F-FET PET and MRI parameters on survival was evaluated subsequently using univariate and multivariate survival estimates. <b>Results:</b> After 2 cycles of adjuvant TMZ chemotherapy, a treatment-induced reduction of MTV and TBR<sub>max</sub> predicted a significantly longer PFS and OS (both <i>P</i> ≤ 0.03; univariate survival analyses) whereas RANO criteria were not significant (<i>P</i> > 0.05). Multivariate survival analysis revealed that TBR<sub>max</sub> changes predicted a prolonged PFS (<i>P</i> = 0.012) and changes of MTV a prolonged OS (<i>P</i> = 0.005) independent of O<sup>6</sup>-methylguanine-DNA-methyltransferase promoter methylation and other strong prognostic factors. <b>Conclusion:</b> Changes of <sup>18</sup>F-FET PET parameters appear to be helpful for identifying responders to adjuvant TMZ early after treatment initiation.