SBRT Sequential Surufatinib Combined With Immunotherapy for Biliary Tract Carcinoma

Inclusion Criteria:

• To be enrolled in this study, patients must meet all of the following criteria:

1. The subjects voluntarily joined the study and signed the informed consent, withgood compliance and follow-up;

2. Age 18-75 years old (including 18 and 75 years old), gender is not limited;

3. Patients with unresectable or untreated recurrent BTC confirmed byhistopathology or cytology (including intrahepatic, extrahepatic, andgallbladder cancers);

4. Have not received any anti-tumor therapy before;

5. Have at least one measurable lesion (according to RECIST 1.1 standards);Magnetic resonance imaging (MRI) enhancement or computed tomography (CT)enhancement were used to accurately measure the diameter ≥10mm, andconventional CT scan was used to measure the diameter at least 20mm.

6. Normal liver volume (total liver volume minus tumor GTV volume) exceeds 1000cc;

7. The maximum diameter of the tumor is less than 10cm, allowing up to 3 satellitefoci. Satellite foci were defined as being less than 2cm and within 1cm of thegross tumor.

8. No serious organic diseases of heart, lung, brain and other organs;

9. The main organs and bone marrow functions are basically normal:

10. Blood routine: white blood cells ≥ 4.0 x 10^9/L, neutrophils ≥ 1.5 x 10^9/L,platelets ≥ 80 x 10^9/L, hemoglobin ≥ 90g/L;

11. International Standardized ratio (INR) and activated partial thromboplastintime (APTT) ≤1.5× upper limit of normal (ULN);

12. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serumtotal bilirubin ≤ 1.5 x ULN after internal/external drainage of obstructivejaundice;

13. Renal function: serum creatinine ≤ 1.5x ULN, creatinine clearance (CCr) ≥ 50mL/min;

14. Normal cardiac function with left ventricular ejection fraction (LVEF)≥50% asmeasured by two-dimensional echocardiography; Fertile male or female patientsvolunteered to use effective contraceptive methods, such as double barriermethods, condoms, oral or injectable contraceptives, and Iuds, during the studyperiod and within 6 months of the last study medication. All female patientswill be considered fertile unless the woman has undergone natural menopause,artificial menopause or sterilization.

Exclusion Criteria:

• The study proposal shall be excluded if any of the following criteria are met:

1. Have received any antitumor therapy in the past (except simple surgicalresection);

2. The tumor directly invades the stomach, small intestine or colon;

3. The maximum diameter of the lesion exceeds 10cm, or the satellite lesion doesnot meet the above definition criteria;

4. Have had other malignancies within the past 5 years, except basal cell orsquamous cell carcinoma of the skin after radical surgery, or carcinoma in situof the cervix;

5. There are extra-hepatic metastases (excluding local regional lymph nodes);

6. Normal liver volume is less than 1000cc;

7. The patient currently has hypertension that cannot be controlled by drugs, asfollows: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90mmHg;

8. Urine routine indicated urinary protein ≥2+, and 24-hour urinary protein volume >1.0g;

9. Patients whose tumors are judged by the investigators to be at high risk ofinvading vital blood vessels and causing fatal massive bleeding during thefollow-up study;

10. Patients with evidence or history of significant bleeding tendency within 3months prior to enrollment (bleeding within 3 months> 30 mL, hematemesis,stool, stool blood), hemoptysis (within 4 weeks > 5 mL fresh blood); Patientswith a history of hereditary or acquired bleeding or coagulation disorders haveclinically significant bleeding symptoms or definite bleeding tendencies within 3 months, such as gastrointestinal bleeding and hemorrhagic gastric ulcers;

11. Clinically significant cardiovascular disease, including but not limited toacute myocardial infarction, severe/unstable angina pectoris, or coronaryartery bypass grafting within 6 months prior to enrollment; New York HeartAssociation (NYHA) Grades for Congestive Heart Failure >Level 2; Ventriculararrhythmias requiring medical treatment; Electrocardiogram (ECG) showed QTCinterval ≥480 ms.

12. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);

13. Women who are pregnant (positive pregnancy test before medication) orbreastfeeding;

14. Any other medical condition, clinically significant metabolic abnormality,physical abnormality or laboratory abnormality, in which, in the investigator'sjudgment, there is reason to suspect that the patient has a medical conditionor condition that is not suitable for the use of the investigational drug (suchas having seizures and requiring treatment), or that would affect theinterpretation of the study results or place the patient at high risk;

15. Known human immunodeficiency virus (HIV) infection; Known history of clinicallysignificant liver disease, including viral hepatitis [Known hepatitis B virus (HBV) carriers must rule out active HBV infection, i.e., positive HBV DNA (>1×104 copies /mL or >2000 IU/ml); known hepatitis C virus infection (HCV) andHCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis];

16. The presence of any active, known or suspected autoimmune disease (includingbut not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemiclupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis,vasculitis, glomerulonephritis, uveitis, pituitaries, hyperthyroidism, etc.);

17. Allergy or suspected allergy to the investigational drug or similar drugs;According to the investigators' judgment, the patients had other factors thatmight affect the study results or lead to the forced termination of the study,such as alcoholism, drug abuse, other serious diseases (including mentalillness) requiring combined treatment, serious laboratory abnormalities, andfamily or social factors that would affect the safety of the patients.