Evaluation of SIRT Followed by Immunotherapy for Treatment of Hepatocellular Carcinoma With Portal Vein Thrombosis

Inclusion Criteria: 1. Age ≥ 18, 2. ECOG Performance Status 0-1, 3. Histologically proven HCC or noninvasive HCC diagnosis according to LiRADS criteria, 4. HCC with Portal vein involvement (PVT), segmental, sectorial or lobar, evaluated by diagnostic imaging (CT scan or MRI), 5. At least one measurable lesion≥ 10mm using mRECIST criteria evaluated by diagnostic imaging, 6. Tumor involvement \<50% of the liver, 7. Hepatic reserve after SIRT ≥ 30% (i.e. hepatic parenchyma not treated with SIRT) evaluated by diagnostic imaging 8. No cirrhosis or Compensated cirrhosis (Child Pugh A, ALBI score 1 or 2), 9. SIRT indication confirmed by a multidisciplinary team meeting (i.e. patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study), 10. Registration with a social security scheme, 11. Written and informed consent of the patient. Exclusion Criteria: 1. Patient with main PVT (partial or complete), 2. Extrahepatic metastases (patients with EHS), except hilum node \< 2 cm, 3. Previous episode of ascites and/or presence of ascites, even if only seen on imaging without clinical detection (except minimum blade only peri-hepatic), 4. Previous episode of hepatic encephalopathy and/or hepatic encephalopathy presence at study entry and/or episodes of encephalopathy (Grade ≥2) within 6 months prior to study inclusion, 5. Pulmonary insufficiency (defined by an arterial oxygen pressure (PaO2) of \<60 mmHg, or oxygen saturation (SaO2) of \<90% (Roussos \& Koutsoukou, 2003) or clinically evident chronic obstructive pulmonary disease (COPD), 6. Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality, 7. Previous HCC therapies: 1. Any prior systemic treatment for HCC; 2. More than 2 prior TACE (or embolization), in the area to be treated; 3. Liver resection or ablation \<6 months from end of previous treatment to TheraSphere administration; 4. Liver ablation \<3 months from end of previous treatment to TheraSphere administration. 8. Prior exposure to immune mediated therapy for HCC or other disease, such as other anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA-4, antibodies, etc. 9. Previous liver radiation (external beam radiation therapy (EBRT) or peptide receptor radionuclide therapy (PRRT) or SIRT 10. Inadequate hematological, hepatic and renal functions: 1. Hemoglobin \<8,5 g/dl; 2. Granulocytes \<1500/mm3; 3. Platelets \< 50 000 /mm3; 4. Bilirubin level ≥35 umol/l; 5. Albumin \<28g/L; 6. Transaminases \> 5 UNL; 7. Creatinine \> 1,5 UNL; 8. INR\>2 (or TP \<60%) without anti-coagulation. 11. Any contraindication to angiography or selective visceral catheterization, 12. History of any organ allograft, including bone marrow allo and autograft, 13. History of active primary/acquired immunodeficiency, that makes patients unsuitable for additional immunotherapy in this study (per investigator), 14. Active or prior documented autoimmune or inflammatory disorders (including but not limited to inflammatory bowel disease \[e.g. ulcerative colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis\]). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia; 2. Patients with hypothyroidism (e.g. following Hashimoto's syndrome) stable on hormone replacement therapy; 3. Any chronic skin condition that does not require systemic therapy; 4. Patients with celiac disease controlled by diet alone. 15. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection), 16. In the case of background systemic corticosteroid use, doses of prednisone or its equivalent \>10 mg/day, 17. Need for premedication of hypersensitivity reactions with Steroids (e.g. CT scan premedication), 18. History of gastrointestinal bleeding within 42 days prior to study inclusion, active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device). Patients with known varices that have not bled or which have been clinically addressed can enter the study. No endoscopic exploration is required before study inclusion, 19. Presence of biliary stent or sphincterotomy within one year prior to study inclusion, 20. History of malignancy, other than HCC, within two years, except the condition is one of the following: 1. Adequately treated carcinoma in situ of the cervix, early squamous cell carcinoma or basal cell carcinoma of the skin, localized prostate cancer, breast ductal carcinoma in situ, or low-grade endometrial carcinoma with no myometrial invasion; 2. Localized prostate cancer under active surveillance; 3. Other cancer when there is a negligible risk of recurrence or progression or death (5-year OS rate \> 90%). 21. Major surgical procedure (as defined by the Investigator) within 42 days prior to study inclusion, 22. A history of severe allergy or intolerance to contrast agents, narcotics, sedatives, or atropine that cannot be managed medically, 23. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients that cannot be managed medically, 24. Active infection, including: 1. Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), 2. HBV\* and Hep D co-infection, 3. Human immunodeficiency virus\*\* (HIV 1/2 antibodies) plus HCV or HBV\* co-infection. * Patients with active HBV infection or HCV infection must be managed according to local standard of care. Patients must show evidence of viral disease stabili