EPIMix is a fast brain MRI technique not previously investigated in patients with glioma grades 3 and 4. This pilot study aimed to investigate the diagnostic performance of EPIMix in the radiological treatment evaluation of adult patients with glioma grades 3 and 4 compared to routine clinical MRI (rcMRI). Patients with glioma grades 3 and 4 investigated with rcMRI and EPIMix were retrospectively included in the study. Three readers (R1-3) participated in the radiological assessment applying Response Assessment for Neuro-oncology Criteria (RANO 2.0), of which two (R1-2) independently evaluated EPIMix and later rcMRI by measuring contrast-enhancing and non-contrastenhancing tumor regions at each follow-up. For cases with discrepant evaluations, an unblinded side-by-side (EPIMix and rcMRI) reading was performed together with a third reader (R3). Comparisons between methods (EPIMix vs. rcMRI) were performed using Weighted Cohen's kappa. The sensitivity and specificity to detect tumor progression (PD) on a follow-up scan were calculated for EPIMix compared to rcMRI with receiver operating characteristic (ROC) curves to assess the area under the curve (AUC). In 35 patients (mean age 53, 31% females), a total of 93 MRIs encompassing 58 follow-up investigations showed PD at blinded reading in 33% of EPIMix (19/58, R1-2), while in 31% (18/58 exams, R1), and 34% (20/58 exams, R2) of rcMRI. An almost perfect agreement for tumor category assessment was found between EPIMix and rcMRI (EPIMixR1 vs. rcMRIR1 ϰ= 0.96; EPIMixR2 vs. rcMRIR2 ϰ= 0.89). The sensitivity for EPIMix to detect PD was 1.00 (0.81-1.00) for R1 and 0.90 (0.68-0.99) for R2, while the specificity was 0.97 (0.86-1.00) for R1-2. The AUC for PD was 0.99 for R1 (EPIMixR1 vs. rcMRIR1) and 0.94 for R2 (EPIMixR2 vs. rcMRIR2), DeLong's test AUCR1 vs. AUCR2 p=0.20 (R1-2). In this pilot study, EPIMix was used as a fast MRI alternative for treatment evaluation of patients with glioma grades 3 and 4, with high, but slightly lower diagnostic performance than rcMRI. CR = complete response; EPIMix = multi-contrast echo-planar imaging-based technique; PD = progressive disease; PR = partial response; RANO = response assessment in neuro-oncology; R1 = reader 1; R2 = reader 2; R3 = reader 3; rcMRI = routine clinical MRI; SD = stable disease.