MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial

PURPOSE: To explore a prognostic or predictive role of MRI and O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. PATIENTS AND METHODS: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial ¹⁸FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. RESULTS: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm³ 0.94; 95% confidence interval (CI), 0.89-0.99] and for higher ADC (HR 0.18; CI, 0.05-0.66). Higher ¹⁸FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High ¹⁸FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16-30.8). CONCLUSIONS: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent ¹⁸FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.