Therasphere® and Systemic Therapy for Patients With Hepatocellular Carcinoma That is High-risk

PRIMARY OBJECTIVES: I. To compare Progression Free Survival (PFS) in patients with advanced HCC who receive Y90 followed by immunotherapy (atezolizumab + bevacizumab, Arm A) or Y90 followed by TKI treatment ( lenvatinib or cabozantinib, Arm B). For ARM B, \[patients will receive Lenvatinib. If they have prior history of treatment with Lenvatinib, then can be given Cabozantinib\].. SECONDARY OBJECTIVES: I. To compare the Time to Progression (TTP) in patients with advanced HCC who receive Immunotherapy combination compared to TKI following Y90. II. To compare the Objective Response Rate (ORR) as assessed by RECIST v1.1 in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90. III. To compare the Duration of Response (DOR) in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90. IV. To compare the Clinical Benefit Rates (CBR) \[CR, PR,SD\] as assessed by RECIST v1.1 in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90. V. To compare the Overall Survival (OS) in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90. VI. To compare the safety and tolerability of patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90, as defined by NCI CTCAEv5. OUTLINE: Patients will first be treated one time with liver directed therapy, Therasphere® (Y-90), following institutional procedures. After completion of Y- 90, patients will have some recovery time (14-21 days) prior to starting systemic therapy. Patients will be followed up for 2 years after completion of study treatment.