Intra-Arterial Super-Selective Delivery of Yttrium-90 for the Treatment of Recurrent Glioblastoma: In Silico Proof of Concept with Feasibility and Safety Analysis

Background: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (90Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT). Methods: Contrast-enhanced T1-weighted magnetic resonance imaging (T1W-MRI) was used to delineate the tumor volumes and CT scans were used to automatically segment the organs at risk in nine patients with recurrent GBM. Volumetric Modulated Arc Therapy (VMAT) treatment plans were generated using a clinical treatment planning system. Assuming the relative intensity of each voxel from the MR-T1W as a valid surrogate for the post-IACI 90Y-PVA-MB distribution, a specific 90Y dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in a 90Y-PVA-MB-based dose distribution that was then compared with the VMAT plans. Results: The physical dose distribution obtained from the simulation of 1GBq of 90Y-PVA-MBs was rescaled to ensure that 95% of the prescribed dose was delivered to 95% or 99% of the target (i.e., A95% and A99%, respectively). The calculated activities were A95% = 269.2 [63.6–2334.1] MBq and A99% = 370.6 [93.8–3315.2] MBq, while the mean doses to the target were 58.2 [58.0–60.0] Gy for VMAT, and 123.1 [106.9–153.9] Gy and 170.1 [145.9–223.8] Gy for A95% and A99%, respectively. Additionally, non-target brain tissue was spared in the 90Y-PVA-MB treatment compared to the VMAT approach, with a median [range] of mean doses of 12.5 [12.0–23.0] Gy for VMAT, and 0.6 [0.2–1.0] Gy and 0.9 [0.3–1.5] Gy for the 90Y treatments assuming A95% and A99%, respectively. Conclusions: 90Y-PVA-MB IACI using MR-T1W appears to be feasible and safe, as it enables the delivery of higher doses to tumors and lower doses to non-target volumes compared to the VMAT approach.