Clinical Study of Radiotherapy Combined With Donafenib for Neoadjuvant Treatment of Patients With HCC With Portal Vein Carcinoma Thrombosis

Inclusion Criteria:

• Age 18 ~ 75 years (inclusive of cut-offs), male or female. Histologically confirmed HCC or meeting the AASLD guidelines for clinical diagnostic criteria for HCC.

Patients with primary HCC without prior systemic therapy (except antiviral therapy) or local therapy and at least 1 measurable lesion meeting the definition of mRECIST criteria.

Chinese primary liver cancer staging (CNLC) IIIa, Cheng's portal PVTT staging type II/III, tumor confined to a single liver lobe, tumor load <50%.

Liver function Child-Pugh score of 5-7. Eastern Cooperative Oncology Group (ECOG) physical status (PS) score 0-1. Expected survival of not less than 3 months. HBV-infected patients with HBV-DNA of ≥104copies/ml within 14 days prior to enrollment, followed by antiviral therapy (entecavir recommended) down to <104copies/ml before study entry, and continued antiviral therapy and monitoring of liver function and serum HBV-DNA levels.

Have adequate organ function reserve and laboratory test values within 14 days prior to treatment must meet the following criteria.

Routine blood tests. Hb≥100 g/L ANC ≥ 1.5×109 /L PLT ≥ 75×109 /L Biochemical examination. ALB ≥28g/L ALT and AST <5×ULN TBIL ≤1.5×ULN Creatinine ≤1.5×ULN or creatinine clearance (Ccr) ≥50 mL/min Creatinine clearance needs to be calculated by the Cockcroft-Gault formula. Men. Creatinine clearance = ((140 age) × body weight (kg))/(72 × serum creatinine (mg/dL)) Females: Male calculation × 0.85. Basic normal electrolytes or normal with treatment. Urine protein <2+ or quantitative 24-hour urine protein test ≤1.0 g/L (for patients with urine protein ≥2+, quantitative 24-hour urine protein test must be ≤1.0 g/L to be enrolled).

Coagulation function. International standard ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN Activated partial clotting time (aPTT) ≤ 1.5 x ULN Patients were voluntarily enrolled, able to provide written informed consent, and able to understand and comply with the trial protocol for medication administration and follow-up.

Exclusion Criteria:

• Pre-existing or co-morbidities.

  1. pathologically confirmed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrous lamellar-like hepatocellular carcinoma.
  2. recurrent hepatocellular carcinoma.
  3. previous local treatment (including hepatectomy, liver transplantation, TACE, HAIC, radiotherapy, etc.) or systemic treatment (except antiviral therapy)
  4. multiple (number of nodules >3) or diffuse intrahepatic nodules
  5. presence of inferior vena cava carcinoma thrombosis, hepatic vein carcinoma thrombosis or bile duct carcinoma thrombosis, extrahepatic metastases or tumor load >50%.
  6. the presence of other malignancies within 5 years, unless the patient has received potentially curative treatment and there has been no evidence of the presence of that disease within 5 years, except that this time requirement (i.e., within 5 years) does not apply to patients with successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other carcinoma in situ
  7. A prior history of serious psychiatric illness.
  8. medical conditions affecting the absorption, distribution, metabolism or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.) Pre-existing or combined medication/treatment.
  9. Have undergone major surgery (as determined by the investigator) within 4 weeks prior to enrollment.
  10. Patients who have received other systemic antitumor therapy prior to enrollment, including other herbal medicines with antitumor indications, for less than 2 weeks or 5 drug half-lives (whichever is longer) after completion of treatment until dosing in this study, or who have not recovered to ≤ CTCAE grade 1 from adverse events caused by preoperative therapy.

  11. Concomitant administration of drugs that may prolong QTc and/or induce tip-twisting ventricular tachycardia (Tdp) or that affect drug metabolism.

      Safety.

  12. Patients with a known or suspected history of allergy to tyrosine kinase inhibitor (TKI) drugs or to excipients of the study drug.
  13. Presence of uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion.
  14. presence of active bleeding or coagulation abnormalities, bleeding tendency or being treated with thrombolytic, anticoagulant or antiplatelet therapy
  15. history of gastrointestinal bleeding within the previous 4 weeks or a definite propensity for gastrointestinal bleeding (e.g., known localized active ulcer lesions, fecal occult blood ++, gastroscopy if persistent fecal occult blood +), or other conditions that may cause gastrointestinal bleeding as determined by the investigator (e.g., severe fundic/esophageal varices).
  16. Gastrointestinal perforation, abdominal fistula or abdominal abscess within the previous 6 months
  17. thrombosis or thromboembolic event within the previous 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.
  18. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within the previous 6 months, congestive heart failure (New York Heart Association NYHA class >2), arrhythmias that are poorly controlled or require pacemaker therapy, hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) that is not controlled by medication.

  19. Active infection, including. Positive for HIV (HIV) (HIV1/2 antibodies). Active hepatitis C (positive HCV antibodies or HCV-RNA ≥ 103 copies/ml and abnormal liver function).

      Active co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). Active tuberculosis. Other uncontrollable active infections (CTCAE V5.0 > grade 2).

  20. Other significant clinical and laboratory abnormalities that, in the opinion of the investigator, affect the safety evaluation, e.g., uncontrolled diabetes mellitus, chronic kidney disease, grade II or higher peripheral neuropathy (CTCAE V5.0), abnormal thyroid function, etc.

  21. Pregnant or lactating women, and female or male patients of childbearing potential who are unwilling or unable to use effective contraception.

      Other.

  22. History of alcohol, psychotropic or other substance abuse within the previous 6 months.
  23. having received another drug or medical device clinical trial within 4 weeks prior to enrollment
  24. Inability to follow the study protocol for treatment or scheduled follow-up.
  25. Any other person who, in the opinion of the investigator, cannot be enrolled in the study.