Combination of SFRT, PD-L1 Inhibitor, and Anti-VEGF in Advanced Hepatocellular Carcinoma

This is a single-arm, single-center, open-label study to evaluate the efficacy and safety of SFRT combined with PD-1 inhibitors (Camrelizumab, Tislelizumab or Sintilimab) and anti-VEGFR (Apatinib or Lenvatinib) in unresectable HCC. Patients received intravenous PD-1 inhibitor 200mg(Camrelizumab, Tislelizumab, or Sintilimab) plus oral Apatinib 250 mg or Lenvatinib 12mg (for bodyweight ≥60 kg) or 8 mg/kg (for bodyweight <60 kg) daily, and additional SFRT for primary liver tumor. PD-1 inhibitor is administered for 2 years or until disease progression or intolerance. Anti-VEGFR is continued until disease progression or intolerance. SFRT implementation plan is as follows: The GTV consists of 2-5 sub-target volumes, which are cylindrical shapes with a diameter of 1.6cm, a height of 2cm, and an interval of 3-5cm. The total volume of the GTV is about 8-20cc, and the distance between the GTV and the OARs is greater than 2cm. The prescribed dosage for each course of radiotherapy is 24 Gy in 3 daily fractions (8Gy x 3F), with a 3-week interval between courses (Q3W). The total courses of radiotherapy shall not be less than 2 (depending on the efficacy and cumulative dose of OARs). The primary endpoint is objective response rate (ORR), and secondary endpoints include overall survival (OS), progression-free survival (PFS), and toxicity.

Inclusion criteria

• Age: 18-75 years old;
• Eastern Cooperative Oncology Group (ECOG) -Performance Status(PS):0-1 points；
• Patient clinically or pathologically diagnosed with hepatocellular carcinoma；
• Advanced hepatocellular carcinoma that is inoperable
• Expected survival period≥3 months;
• Liver function grade Child-Pugh A or better grade B (7 points);

Exclusion criteria

• Prior invasive malignancy unless disease-free for a minimum of 2 years
• Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
• Prior selective internal radiotherapy/ablation, at any time
• Untreated active hepatitis B or hepatitis C
• Moderate to severe or intractable ascites
• Untreated or incompletely treated esophageal or gastric varices
• Severe, active co-morbidity, defined as follows:

Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration Myocardial infarction within the last 6 months prior to study entry Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry A bleeding episode within 6 months prior to study entry due to any cause. Thrombolytic therapy within 28 days prior to study entry. Known bleeding or clotting disorder. Uncontrolled psychotic disorder

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior solid organ transplantation.
• Immunodeficiency diseases (including HIV) or autoimmune diseases require systemic immunosuppressive therapy (prednisone dosage>10mg per day)
• Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation.