Adjuvant Therapy for High-Risk Intrahepatic Cholangiocarcinoma: A Real-World Study

Inclusion Criteria:

• Histologically confirmed ICC within 12 weeks after curative resection
• Any T stage; N0/N+; M0.
• At least one high-risk factor:

Preoperative tumor penetration of the liver capsule or extrahepatic direct invasion; Preoperative imaging showing multifocal lesions or a single lesion >5 cm; Vascular invasion (preoperative or postoperative pathology); Regional lymph node metastasis.

• No prior systemic therapy for ICC.
• ECOG performance status 0-2.
• Expected survival ≥3 months.
• Adequate organ function.
• Agreement to use effective contraception (or surgical sterilization) during the study and for 120 days after the last dose.
• Signed informed consent and anticipated good compliance with the study protocol.

Exclusion Criteria:

• Immunosuppressive therapy within 28 days prior to enrollment (excluding topical/inhaled corticosteroids or physiologic steroid doses ≤10 mg/day prednisone equivalent).
• Systemic anticancer herbs/immunomodulators (e.g., thymosin, interferons) within 4 weeks, except for pleural effusion control.
• Uncontrolled cardiovascular disease:

Unstable angina/myocardial infarction Arrhythmias with QTc ≥450 ms (men) or ≥470 ms (women) NYHA Class III-IV heart failure or LVEF <50%

• Active infections (IV antibiotics/antivirals required) or fever >38.5°C within 4 weeks; or major surgery within 3 weeks.
• Active autoimmune/immunodeficiency diseases (e.g., hepatitis, pneumonitis, rheumatoid arthritis), except:

Hypothyroidism on stable hormone replacement Type 1 diabetes with controlled glucose Uncontrolled asthma requiring systemic bronchodilators (resolved childhood asthma allowed).

- Active infections: HIV/AIDS

HBV (DNA ≥500 IU/mL) or HCV (RNA-positive) unless:

HBV DNA <500 IU/mL + antiviral therapy ≥14 days

• Prior/proposed organ transplantation (excluding corneal grafts).
• Concurrent interventional trials or investigational drugs within 4 weeks without recovery to Grade ≤1 toxicity.
• Hypersensitivity to study drug components.
• Allogeneic transplant history/plans.
• Uncontrolled psychiatric/substance abuse disorders.
• Refractory hypertension (≥140/90 mmHg despite treatment).
• Clinically significant bleeding/thromboembolism:

GI bleeding within 3 months Thrombotic events within 6 months (stroke, DVT/PE)

• Coagulopathy (INR >1.5, PT >ULN+4s, aPTT >1.5×ULN) or anticoagulant use.
• Proteinuria ≥++ on dipstick or 24-h urine protein ≥1 g.
• Other high-risk conditions per investigator judgment.