Phase 1 Yttrium-90 (beta-emitting glass microspheres) radioembolization dose-escalation in unresectable liver tumors

Northwestern University’s MARGIN Study is a prospective, non-randomized, open-label dose-escalation trial designed to define an “ablative” absorbed-dose range for yttrium-90 (Y-90) transarterial radioembolization (radiation segmentectomy), where the MOA is catheter-delivered beta radiation from Y-90–loaded glass microspheres lodging in tumor-feeding arterioles. Two parallel arms reflect baseline liver reserve: patients with cirrhosis start at 300 Gy and those without cirrhosis start at 200 Gy, escalating in 100 Gy increments (target range 200–500 Gy) with safety overseen by a Data Safety Monitoring Committee and a Bayesian optimal interval approach. The population includes unresectable hepatocellular carcinoma, cholangiocarcinoma, and liver-dominant metastatic cancers not amenable to surgery or standard ablation. A key angle is integrating voxel-based Y-90 PET dosimetry plus hepatobiliary/functional MRI endpoints to connect delivered dose to structural and functional “complete sectoral ablation,” aiming for a more reproducible, curative-intent segmentectomy playbook. Today’s care typically mixes systemic therapy (immunotherapy/targeted therapy depending on histology/mutations), plus locoregional options like TACE, Y-90, or external-beam RT when feasible; this study specifically optimizes the radiation segmentectomy dose window rather than comparing modalities.