Background: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma (Graillon et al. 2021). This classification segregates meningioma response into three main classes and a total of five subclasses (class 1 = volume decrease ≥ 25%; 2A = tumor stabilization; 2B = 3DVGR severe slowdown; 3A and 3B = respective low and quick progression) based on the 3DVGR before and under treatment. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the use of trabectedin for recurrent WHO 2 or 3 meningioma (Preusser et al. 2022). Objective: To evaluate the discriminative value of 3DVGR classification for response and clinical benefit prediction in the EORTC-BTG-1320 clinical trial. Methods: All patients with at least one available additional MRI before inclusion were included. 3D volume was evaluated on all consecutive MRI until progression. 3DVGR classification was applied on them as previously described. Clinical benefit was defined as neurological and/or functional status improvement and/or steroid decrease or discontinuation. Results: 17 patients were included in this post-hoc analysis with a median age of 58 years (range, 38-73). Treatments were trabectedin, bevacizumab, hydroxyurea or palliative care in 9, 3, 2 and 3 patients respectively. At first evaluation, 3DVGR classes were 1, 2A, 2B, 3A, 3B and not evaluable in 8%, 15%, 8%, 23%, 38% and 8%, respectively. Best 3DVGR classification was 1, 2A, 3A, 3B and not evaluable in 15%, 31%, 15%, 31% and 8%, respectively. 3DVGR did not differ by methylation subgroups and NF2 or CDKN2A alterations. All patients with progression-free survival longer than 6 months presented with best 3DVGR class 1 or 2. In contrast, all patients with PFS shorter than 6 months presented with best 3DVGR class 3 or not evaluable due to early progression. Median overall survival was 34.7 months for the entire cohort. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3. Best objective response according to modified Macdonald response criteria were stable disease, progression or undetermined in 8, 6 and 3 patients respectively. Regarding the 8 stable patients, they were segregated into classes 1, 2, 3 or undetermined by the 3DGVR classification in 2, 4, 1 and 1 patients, respectively. Finally, all class 1 patients, 75% of class 2 patients and only 17% of class 3 patients presented with clinical benefit (neurological and/or functional status improvement and/or steroid decrease or discontinuation), respectively. Conclusions: Tumor 3DVGR classification may be helpful to discriminate early signal of treatment activity in an independent randomized phase II clinical trial. Clinical trial information: NCT02234050.