Table 1 Patient eligibility criteria for DOORwaY90 trial

Willing, able, and mentally competent to provide written informed consent

Age 18 or older at the time of consent

Diagnosis of HCC with Liver Imaging Reporting and Data System (LI-RADS) 4 or 5 or by histology

Treatment-naïve patients, including no prior locoregional therapies in the liver and no systemic therapy for HCC

BCLC stage A, B1, B2, and C with maximal single tumor size of ≤ 8 cm and sum of the maximal tumor dimensions of ≤ 12 cm, with the entire tumor burden expected to be treatable within the perfused volume

All tumors must be measurable by CT or MRI according to localized mRECIST

At least one lesion ≥ 2 cm in diameter (long axis) measured according to mRECIST criteria by CT or MRI

Child Pugh score A5 or A6 at baseline

Albumin-Bilirubin (ALBI) grade = 1 or 2 at baseline

Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 at baseline

Adequate blood count, liver enzymes, and renal function at baseline

 Platelet count > 50,000/µl (no platelet transfusion or growth factors)

 White blood cell count ≥ 3 × 10⁹/l

 Hemoglobin >8.5 g/dl

 AST and ALT <5 × upper limit normal

 Bilirubin ≤ 2.0 mg/dl

 Albumin >3.0 g/dl

 Creatinine <2.0 mg/dl

 INR ≤ 2.0

 Glomerular filtration rate > 50

Negative serum pregnancy test at baseline

Life expectancy of ≥ 6 months with life expectancy of > 3 months if receiving no active treatment

Patient eligible for ablation or resection for their malignancy in the opinion of the investigator at screening visit

Prior systemic anti-cancer therapy (including immunotherapy and/or targeted therapy), radiotherapy or use of other investigational agents for the treatment of HCC

Intrahepatic arteriovenous shunting. (arteriovenous shunting resulting from a biopsy is allowed but must be embolized during the pre-treatment mapping procedure)

Incompetent biliary duct system, prior biliary intervention or a compromised Ampulla of Vater

Planned localized cancer treatment to the liver, other than the study treatment, during the study

Planned systemic cancer treatment during the study

Portal vein thrombosis

Extrahepatic disease

Patients with contraindications to angiography and selective visceral catheterization

Evidence of extrahepatic collateral supply to the tumor

Evidence of potential delivery of mean radiation dose > 30 Gy to the lungs (single treatment)

Evidence of any detectable ^99mTc-MAA flow to outside of the liver in the abdomen, after application of established angiographic techniques to stop or mitigate such flow (e.g., placing catheter distal to gastric vessels or coiling)

Evidence that < 33% of the total liver volume is disease-free and will be spared ⁹⁰Y resin microsphere treatment

Prior liver resection and/or liver transplant

Female patients who are pregnant, breastfeeding, or premenopausal and unwilling to use an effective method of contraception through the 1-year follow-up; males unwilling to use effective method of contraception for 30 days post-procedure

Medical history of clotting disorders

Underlying pulmonary disease requiring chronic oxygen therapy

Evidence of portal hypertension with ascites as seen on cross-sectional imaging or history of variceal bleeding within 6 months before screening

Concurrently enrolled in another study unless it is an observational, non-interventional study

Active infection (hepatitis B (HBV) infection with ongoing HBV treatment and successfully treated hepatitis C infection is allowed)

History of other cancer with current active treatment

Patients with drug or alcohol dependency (within 6 months of study entry) in the opinion of the investigator

History of severe allergy or intolerance to contrast agents, narcotics, or sedatives

Any condition that, in the opinion of the investigator, would interfere with safe delivery of the study treatment or with the interpretation of study results