Selective Internal Radiation Therapy (SIRT) Using SIR-Spheres® Y-90 Resin Microspheres on DoR & ORR in Unresectable Hepatocellular Carcinoma Patients

Inclusion Criteria:

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

2. Age 18 or older at the time of consent

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

4. Life expectancy ≥ 6 months (to allow for adequate completion of study procedures andcollection of data)

5. Diagnosis of HCC with Liver Imaging Reporting and Data System (LIRADS) 4 or 5 or byhistology

6. Treatment-naïve patients or patients who have developed a new lesion following oneof these prior locoregional treatments:

7. Liver resection with negative pathologic margins, no microvascular invasion,and no recurrence at resection margins for at least 6 months post-treatment andno new lesions within 6 months of liver resection

8. Ablation of a single ≤3cm lesion with no recurrence of the treated lesion forat least 6 months post-treatment

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

10. At least one lesion ≥1 cm in diameter (long axis) measured according to mRECISTcriteria by CT or MRI

11. Child-Pugh score of A5 or A6 at baseline

12. Eastern Cooperative Oncology Group (ECOG) performance score of ≤1 at baseline

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

14. Platelet count >50,000/microliter (patients may not receive a platelettransfusion or growth factors to increase the platelet count so that thepatient may be eligible for the study)

15. White Blood Cell (WBC) ≥ 3 x 10^9/L

16. Hemoglobin > 8.5 g/dL

17. Aspartate transaminase (AST) & Alanine transaminase (ALT) < 5 x upper limitnormal

18. Bilirubin ≤ 2.0 mg/dL

19. Albumin > 3.0 g/dL

20. International normalized ratio (INR) ≤ 2.0

21. Glomerular filtration rate (GFR) > 50

22. Negative serum pregnancy test at baseline

23. Life expectancy of > 3 months without any active treatment

Exclusion Criteria:

1. Patients eligible for ablation or resection for their malignancy, in the opinion ofthe investigator, at the time of screening

2. Prior systemic anti-cancer therapy (including immunotherapy and/or targetedtherapy), radiotherapy or use of other investigational agents for the treatment ofHCC

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

4. Incompetent biliary duct system, prior biliary intervention or a compromised Ampullaof Vater

5. Planned localized cancer treatment to the liver, other than the study treatment,throughout the duration of the study.

6. Planned systemic cancer treatment throughout the duration of the study

7. Patients with portal vein thrombosis

8. Patients with extrahepatic disease

9. Patients with contraindications to angiography and selective visceralcatheterization

10. Evidence of extrahepatic collateral supply to the tumor

11. Evidence of potential delivery of mean radiation dose > 30 Gy to the lungs (singletreatment)

12. Evidence of any detectable 99m Tc-macroaggregated albumin (99m Tc-MAA) flow outsideof the liver in the abdomen, after application of established angiographictechniques to stop or mitigate such flow (e.g., placing catheter distal to gastricvessels or coiling)

13. Evidence that < 33% of the total liver volume is disease-free and will be sparedSIR-Spheres treatment

14. Prior liver resection and/or liver transplant, with exception for patients withprior resection who meet inclusion criterion 6a

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

16. Medical history of clotting disorders

17. Underlying pulmonary disease requiring chronic oxygen therapy

18. Evidence of portal hypertension with ascites as seen on cross-sectional imaging orany history of prior variceal bleeding within 6 months prior to screening

19. Concurrently enrolled in another study unless it is an observational,noninterventional study

20. Active infection (hepatitis B (HBV) infection with ongoing HBV treatment andsuccessfully treated hepatitis C infection are allowed)

21. History of other cancer with current active treatment

22. Patients with drug or alcohol dependency (within 6 months prior to study entry) inthe opinion of the investigator

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

24. Any condition that, in the opinion of the investigator, would interfere with safedelivery of the study treatment or with the interpretation of study results