• In 1951, Bierman et al demonstrated angiographically that liver tumors received their blood supply from the hepatic artery and not the portal vein.

• 1967, Ariel & Pack perform first Y90 administration in four patients

1999: TheraSphere granted a humanitarian device exemption for use in patients with unresectable HCC.

2016: SIR-Spheres approved for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intrahepatic artery chemotherapy.

2025: SIR-Spheres for the treatment of unresectable hepatocellular carcinoma (HCC) following the DOORwaY-90 study

• Phase III, open-label, randomized controlled trial

• \(^{90}\)Y Resin Microspheres vs. Sorafenib for advanced HCC (BCLC C)

• No significant difference in overall survival (8.0 months for Y90 vs. 9.9 months for sorafenib)

• Radioembolization associated with fewer adverse events and better quality of life

• Phase III, open-label, randomized controlled trial

• \(^{90}\)Y Resin Microspheres vs. Sorafenib for advanced HCC (BCLC B or C) in the Asia-Pacific

• No significant difference in overall survival (8.8 months for Y90 vs. 10.0 months for sorafenib)

• Radioembolization showed significantly fewer grade 3 adverse fewer adverse events (27.7% vs. 50.6%)

• Phase III, open-label, randomized controlled trial

• Personalized Dosimetry (≥205 Gy target) vs. Standard Dosimetry (∼120 Gy target)

• Personalized dosimetry showed higher median overall survival (26.6 months for vs. 10.7 months)

• Also showed higher tumor responses response rates (71% vs. 36%) and increased rates of downstaging to surgical treatments (35% vs. 3.5%)
  

• Y90 Radioembolization vs. Drug-Eluting Bead Chemoembolization (DEB-TACE)

• The trial was stopped early because the primary endpoint (TTP) was met in favor of Y90

• Y90 TARE showed superior median overall (30.2 months vs. 15.6 months)

Superselective infusion of a very high dose (> 400 Gy)

Evidence:

• LEGACY trial: ORR 90%, median OS ~45 months

Pearls:

• Identify variant anatomy (parasitizing supply, accessory/replaced vessels)
• Different segments are associated with different post-embolization complications

Lobar dose to induce hypertrophy of the contralateral lobe

Alternative to portal vein embolization

Provides tumor control while waiting for future liver remnant (FLR) growth

Old model: everyone gets the same dose

Modern model

• 99mTc-MAA SPECT/CT

• Voxel- or partition-based dosimetry

• Targeted dose delivery

Evidence

• DOSISPHERE-01: OS 10.7 → 26.6 mo

• Child-Pugh A and early B

• Liver-dominant disease

• Assess vascular anatomy and shunting

• Multidisciplinary input with hepatology and surgery

• Selective catherization

• Identify variant hepatic arterial anatomy

• Coil embolization of gastroduodenal or right gastric artery

• MAA injection to estimate lung shunt and dosimetry

• Selective catheterization

• Deliver microspheres slowly under fluoroscopy

• Post-treatment SPECT or PET imaging