Assessment of Response to Regorafenib in Patients with Glioma Relapse Using ¹⁸F-FET PET and MRI

Neuroimaging markers predicting response to regorafenib in patients with glioma relapse remain scarce; we evaluated whether early changes in amino acid PET and MRI are associated with overall survival (OS). Methods: Twenty adult patients with central nervous system World Health Organization grade 3 or 4 gliomas at relapse (glioblastoma, 85%) were treated according to the REGOMA trial. Amino acid PET using the tracer O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (¹⁸F-FET) and MRI were performed at baseline and after 2 cycles. From these imaging data, tumor-to-brain ratios (TBR), metabolic tumor volumes, the dynamic parameters (time to peak and slope), and apparent diffusion coefficients were obtained. Parameter thresholds to predict an OS of 6 mo or longer as a surrogate for response were defined using receiver operating characteristic curve analyses. In addition, Response Assessment in Neuro-Oncology criteria for MRI and PET were used to evaluate response. The association of imaging parameters with OS was evaluated using univariate and multivariate survival estimates. Results: Patients received a median of 3 regorafenib cycles (range, 2-16 cycles). The median follow-up was 10.3 mo (range, 3.2-27.6 mo). A decline in mean TBR values by 10% or greater was significantly associated with longer OS (10.4 vs. 5.3 mo; P = 0.027). Other ¹⁸F-FET PET parameters, Response Assessment in Neuro-Oncology criteria for MRI and PET, and apparent diffusion coefficient values were not associated with OS (P > 0.05). At follow-up, a mean TBR of 2.0 or less was associated with longer OS (10.6 vs. 4.5 mo; P = 0.009). Multivariate survival analyses revealed that changes in mean TBR values were independently associated with longer OS (P = 0.006; hazard ratio, 0.200), and a lower mean TBR at follow-up was strongly prognostic (P < 0.001; hazard ratio, 0.030). Conclusion: ¹⁸F-FET PET parameters are clinically valuable for identifying responders to regorafenib early after treatment initiation.