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

in Pharmaceutics by Giulia Paolani, Silvia Minosse, Silvia Strolin, Miriam Santoro, Noemi Pucci, Francesca Di Giuliano, Francesco Garaci, Letizia Oddo, Yosra Toumia, Eugenia Guida, Francesco Riccitelli, Giulia Perilli, Alessandra Vitaliti, Angelico Bedini, Susanna Dolci, Gaio Paradossi, Fabio Domenici, Valerio Da Ros, Lidia Strigari

TLDR

  • Y-PVA-MB IACI is a promising treatment option for GBM recurrence that delivers high doses to tumors and low doses to non-target volumes
  • Future studies will investigate the clinical efficacy and safety of Y-PVA-MB IACI in patients with recurrent GBM
  • Standardized protocols for Y-PVA-MB IACI treatment planning and delivery will be developed and validated in clinical trials

Abstract

: 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 (Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT).: 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-IACIY-PVA-MB distribution, a specificY dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in aY-PVA-MB-based dose distribution that was then compared with the VMAT plans.: The physical dose distribution obtained from the simulation of 1GBq ofY-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 theY-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 theY treatments assuming A95% and A99%, respectively.:Y-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.

Overview

  • The study investigated the feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (Y-PVA-MB) Intra-arterial cerebral infusion (IACI) for glioblastoma (GBM) recurrence
  • The study compared the results with those of external beam radiation therapy (EBRT) and used Volumetric Modulated Arc Therapy (VMAT) treatment plans as a reference
  • The primary objective was to evaluate the delivery of high doses to tumors and low doses to non-target volumes using Y-PVA-MB IACI

Comparative Analysis & Findings

  • The study found that Y-PVA-MB IACI enables the delivery of higher doses to tumors compared to VMAT, with a median dose of 123.1 [106.9-153.9] Gy and 170.1 [145.9-223.8] Gy for A95% and A99%, respectively
  • Non-target brain tissue was spared in the Y-PVA-MB treatment compared to the VMAT approach, with a median mean dose of 0.6 [0.2-1.0] Gy and 0.9 [0.3-1.5] Gy for A95% and A99%, respectively
  • 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

Implications and Future Directions

  • The study suggests that Y-PVA-MB IACI is a promising treatment option for GBM recurrence, enabling the delivery of high doses to tumors and low doses to non-target volumes
  • Future studies should investigate the clinical efficacy and safety of Y-PVA-MB IACI in patients with recurrent GBM
  • Standardized protocols for Y-PVA-MB IACI treatment planning and delivery should be developed and validated in clinical trials