此临床试验旨在比较序贯经动脉化疗栓塞（TACE）及立体定向身体放射治疗（SBRT）与Y90放射栓塞（SIRT）后接续全身治疗，在大型、局部晚期、不可切除肝细胞癌（HCC）患者中的安全性及疗效。 其主要旨在回答的问题是序贯TACE-SBRT能否潜在带来更长的无进展生存期（PFS）获益。
适应症：Hepatocellular Carcinoma (HCC)
入组条件
纳入标准
- Patients diagnosed with HCC either by histology or by the American Association for the Study of Liver Diseases Criteria (AASLD) 2018
- Patients age 18-80 years of age with HCCs deemed unresectable at the Multidisciplinary Team Meetings (MDTs) because of the following:
- R0 resection not feasible e.g. unfavourable tumour location
- Remnant liver volume \<30% in non-cirrhotic patients or 40% in cirrhotic patients
- Indocyanine green test \>15%
- Patients with Barcelona Clinic Liver Cancer (BCLC) stage B2-4 (unresectable group) or C
- Tumour sizes of ≥5cm, of which ≥1 is a measurable lesion as defined by the mRECIST criteria
- Subjects aged 18-80 years of age
- ECOG performance status of 0-1
- Predicted life expectancy should be of ≥ 3 months
- Child Pugh (CP) score of A5-B7
- Adequate organ and marrow functions, as listed below:
- Haemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1,500/uL
- Platelet count ≥100,000/L
- Total bilirubin ≤2.0 x upper limit of normal (ULN)
- Albumin ≥2.8 g/dL
- ALT ≤3 x ULN
- INR ≤1.6
- Calculated creatinine clearance (eGFR) ≥45 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance
- Liver volume minus intrahepatic gross tumour volume (GTV) with \>700cc
- Patients with concomitant HBV infection (defined as having HBsAg positive and/or detectable HBV DNA level) must be treated with antiviral therapy (per local institutional practice) to ensure adequate viral suppression (defined as HBV DNA \<2,000 IU/mL) prior to enrolment, throughout study duration and continue for at least 6 months following the last dose of local-systemic therapy
- Informed consent provided
- Females of childbearing potential or non-sterilized male who are sexually active must use a highly effective method of contraception
- Females of childbearing potential must have negative serum or urine pregnancy test
排除标准
- Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
- Presence of any extra-hepatic metastases
- Presence of main portal vein (PV) or inferior vena cava (IVC) involvement
- Presence of active, uncontrolled varices
- Presence of active, severe comorbidities including uncontrolled cardiovascular or cerebrovascular diseases or recent events within 6months prior to treatment
- Received prior non-curative locoregional (including TACE, RT to liver, SIRT) or systemic therapy received for HCC\\
- Prior treatment with any anti-programmed cell death protein-1 (anti-PD-1), PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent, or an antibody targeting other immune-regulatory receptor(s) or mechanism(s)
- Use of chronic systemic steroid or any other immunosuppressive medication within 14days prior to treatment initiation, except:
- Intranasal, inhaled, topical steroids, or local steroid injection;
- Systemic corticosteroids at physiologic doses ≤10mg/day of prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions
- Active or documented autoimmune or inflammatory disorders within 2years, except diabetes type I, vitiligo, psoriasis, or hypo-/hyperthyroid diseases not requiring immunosuppressant(s)
- Known history of a positive HIV test, primary/acquired immunodeficiency syndrome, or solid organ transplantation
- Receipt of live, attenuated vaccine within 28 days prior to study treatment
- Severe hypersensitivity reaction to another monoclonal antibody
- Presence of any contraindication to TACE not otherwise listed: cisplatin allergy
- Presence of any contraindication to SBRT not otherwise listed:
- Maximal size of any one HCC \>25 cm
- Direct tumour extension into gastrointestinal structures (stomach, duodenum, remaining small or large bowel)
- Presence of any contraindication to SIRT not otherwise listed:
- Pre-treatment 99mTc-MAA scan \>20% lung shunting of hepatic artery blood flow, or a demonstration of radiation exposure to the lungs potentially \>25Gy
- Pre-treatment hepatic angiogram showing potential Y90 microspheres deposition in the gastrointestinal tract or any other organ(s) which is not correctable by catheter embolization techniques.
- Pregnant or lactating females
入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。