Efficacy and Safety of SBRT Plus Gemcitabine, Cisplatin, and Sintilimab as First-Line Treatment for Unresectable Biliary Tract Cancer

According to current clinical guidelines, first-line treatment for advanced biliary tract cancer (BTC) is the gemcitabine plus cisplatin (GC) regimen combined with immunotherapy, which has been shown to improve patient outcomes. Additionally, the combination of radiotherapy and immunotherapy may synergistically enhance antitumor efficacy. Therefore, this study aims to assess the efficacy and safety of first-line treatment with radiotherapy in combination with sintilimab and gemcitabine/cisplatin versus sintilimab in combination with gemcitabine/cisplatin in patients with previously untreated, unresectable locally advanced or metastatic BTC.

Inclusion Criteria: 1. Patients voluntarily provide written informed consent, with authorization obtained from the patient or legal representative prior to any protocol-related procedures. 2. Age ≥ 18 years and ≤ 75 years; both female and male 3. Histologically or cytologically confirmed, unresectable advanced or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma. 4. No prior systemic anti-tumor treatment for BTC. Patients who developed recurrent disease \>6 months after surgery with curative intent and, if given, \>6 months after the completion of neo/adjuvant therapy (chemotherapy and/or radiation) will be eligible. 5. At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline. 6. ECOG performance status of 0 or 1. 7. Life expectancy ≥12 weeks. 8. Adequate organ and bone marrow function within 14 days prior to initiation of study treatment, defined as follows: a.Hematology (without transfusion, granulocyte colony-stimulating factor \[G-CSF\], or other correction treatment within 14 days prior to screening): i.Hemoglobin \[HB\] ≥ 90 g/L; ii.Absolute neutrophil count \[ANC\] ≥ 1.5 × 109/L; iii.platelet count (PLT) ≥ 75 × 109/L b.Biochemistry Examination (without albumin infusion within 14 days prior to screening): i.Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (for patients with Gilbert's syndrome, ≤ 3 × ULN) ii.alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN; iii.serum creatinine (Cr) ≤ 1.5 × ULN or clearance of creatinine (CCr) ≥ 50 mL/min (Cockcroft-Gault formula); * Male: Creatinine clearance rate = \[(140 - age) × weight\] / (72 × serum Cr) * Female: Creatinine clearance rate= \[(140 - age) × weight\] / (72 × serum Cr) × 0.85 (Weight unit: kg; serum Cr unit: mg/dL) 9. Patients with evidence of hepatitis B virus (HBV) infection, defined as detectable HBV DNA (≥10 IU/mL or above the lower limit of detection according to local laboratory standards) and positive HBsAg and/or anti-HBc, must receive antiviral therapy prior to study drug administration in accordance with institutional practice to ensure adequate viral suppression. Antiviral therapy must be continued throughout the study period and for at least 6 months after the last dose of study treatment. Patients who are anti-HBc positive but HBV DNA negative (\10 mg prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to first dose of study intervention. 13. History of gastrointestinal bleeding within 6 months prior to study treatment, documented predisposition to gastrointestinal hemorrhage, or known hereditary or acquired bleeding (e.g., coagulopathy) or thrombotic tendency. 14. Major surgery (excluding biopsy) with incomplete recovery from surgery or surgical complications, or incomplete wound healing, prior to start of study intervention, or anticipated need for major surgery during the study period. 15. Receipt of live attenuated vaccine within 28 days prior to first dose of study intervention, or anticipated need for live attenuated vaccine during study treatment or within 60 days after last dose. 16. Any other condition judged by the investigator to potentially interfere with study outcomes or lead to premature study termination, including alcohol or drug abuse, severe comorbidity requiring concomitant therapy (including psychiatric illness), severe laboratory abnormality, or family or social factors affecting patient safety or data collection.