Efficacy and Safety of Yttrium-90 Microspheres Selective Internal Radiotherapy Combined with Immune Checkpoint Inhibitors and Anti-angiogenesis Drugs Sequential HAIC for Hepatocellular Carcinoma

Inclusion Criteria:

* ≥18 and ≤75 years of age, regardless of gender;
* Hepatocellular carcinoma (HCC) diagnosed clinically or pathologically with the following characteristics and assessed by the investigator to be initially not amenable to surgical resection but with the potential for surgical resection after conversion therapy;
* The tumour is confined to a unilateral hepatic lobe, with no extrahepatic metastases and no clinical evidence of high pressure on the imperial vein;
* CNLC stage Ib-IIIa;
* ECOG PS score: 0-1;
* At least one measurable lesion according to mRECIST criteria;
* Child-Pugh A;
* For patients with active hepatitis B virus (HBV): HBV-DNA must be \<2,000 IU/mL and must have received at least 14 days of anti-HBV treatment (based on current guidelines, e.g., entecavir) prior to the start of study treatment and be willing to receive antiviral treatment for the full duration of the study; HCV-RNA-positive patients must receive antiviral treatment according to guidelines; and HCV-RNA-positive patients must receive antiviral treatment according to guidelines. HCV-RNA-positive patients must be receiving antiviral therapy according to guidelines and have liver function within CTCAE class 1 ascending;
* No severe fluid, renal, or coagulation dysfunction:

  1. Gynecological examination (excluding the use of any gynecological fluid component and cell growth within 14 days) 1) Neutrophil count (NE) \>1.5 x 109/L; 2) Glucose count (NE) \>1.5 x 109/L; 3) Glucose count (NE) \>1.5 x 109/L; 2) Hemoglobin count (HGB) \>90 g/L; 3) Platelet count (PLT) \>75×109/L;
  2. Liver and kidney function:

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  1. Serum creatinine ≤2.0×ULN;
  2. Total bilirubin (TBIL) ≤ 2.0 × ULN;
  3. Aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN;
* Completion of 99mTc-MAA and SPECT/CT to meet the treatment requirements for 90Y-SIRT, including but not limited to: (1) pulmonary shunt fraction \<20%; (2) single pulmonary absorbed dose \<25Gy or cumulative pulmonary absorbed dose \<30Gy (Twice Y90 Treatment interval 4-6 weeks);
* An expected life expectancy of ≥3 months;
* No previous treatment with transhepatic arterial embolisation (TAE, cTACE or D-TACE), targeted therapy, immunotherapy, radiotherapy or pellet implantation, or SIRT;
* Women of childbearing potential must have a negative pregnancy test (serum) or urine HCG test within 7 days prior to enrolment and be willing to use appropriate contraception during the trial and for 8 weeks after the last dose of the test drug; for men, they should be surgically sterilised or agree to use appropriate contraception during the trial and for 8 weeks after the last dose of the test drug;
* The patients were willing to enter the study and signed an informed consent form.

Exclusion Criteria:

* Known fibroplaque HCC, hydatidiform HCC, or mixed hepatocellular carcinoma;
* Refractory ascites (despite optimal diuretic therapy) or any other clinical signs of liver failure;
* Untreated or incompletely treated hydronephrosis and/or fundal varices or those at high risk of bleeding as assessed by the investigator, or a history of bleeding due to hydronephrosis or fundal varices within 1 month prior to entry;
* Major surgical treatment or chemotherapy, radiotherapy or other systemic treatment of the lesion within 1 month prior to entry;
* Previous allogeneic nickel-hydride cell or solid organ transplantation;
* Active autoimmune disease requiring systemic therapy (use of palliative medications, steroids, or immunosuppressants); or Thymosin-α1, etc.) within 30 days of the study.
* Have received a live attenuated vaccine within 4 weeks prior to the study, or expect to receive such a vaccine during treatment or within 5 months of the last dose.
* Uncontrolled medical conditions including, but not limited to, persistent infections (other than viral hepatitis), symptomatic cardiac failure, unstable heartburn, colic, cardiac arrest, and heartburn.Uncontrolled medical conditions include, but are not limited to, persistent infections (except viral hepatitis), symptomatic cardiac failure, unstable cardiac colic, irregular heartbeat or severe mental illness;
* Uncontrolled high blood pressure (systolic \> 150 mmHg and/or diastolic \> 100 mmHg). 10. other active malignant tumours;
* Other active malignancies (completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer).Other active malignancies (except completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder carcinoma, and any other cancer that has not recurred for at least 5 years);
* A history of allergy to therapeutic agents and compounds of similar composition;
* Contraindications to study drug or SIRT therapy, or to angiography as assessed by the Investigator;
* Pregnant or lactating women and those planning to conceive;
* Have participated in other research studies in the last 3 months;
* Inability to understand or unwillingness to sign a written informed consent form.