Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion

Inclusion Criteria:

• Patients with HCC meeting all of following criteria;

1. Histologically or radiologically confirmed hepatocellular carcinoma based onthe guidelines of the Korean Liver Cancer Association-National Cancer Center 2022

2. Age >= 20

3. Vp2-4 portal vein tumor thrombosis diagnosed by dynamic enhanced computedtomography (CT) or maganetic resonance images (MRI) with below finding 1) anintraluminal filling defect adjacent to the primary tumor in Vp2-4 portal vein

2. an enhancement of the filling defect on arterial phase and a washout onportal/delayed phases.

4. Signed written informed consent

5. at least one or more measurable intrahepatic viable HCC lesions

6. Child-Pugh class A within 2 weeks from screening for study registration

7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration

8. Life expectancy of at least 16 weeks

9. adequate bone marrow and liver function within 2 weeks from screening for studyregistration

• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000/mm3
• Platelet count ≥ 50,000/μL
• Total bilirubin < 2.5 mg/dL
• Serum albumin >2.8 g/dL
• Alanine aminotransferase (ALT) and aspartateaminotransferase (AST) ≤ 5 × upper limit ofnormal (ULN)
• Prothrombin time in INR ≤ 1.8 × ULN
• Serum creatinine ≤ 1.5 mg/dL

10. Women of childbearing potential and men must agree to use highly efficientcontraception since signing of the informed consent form until at least 6months (women) and 7 months (men) after the last study drug administration

11. If other selection conditions are satisfied and the exclusion criteria are notmet, registration is possible even in case of N1 or M1.

12. Registration is possible even in the case of hepatic vein tumor infiltration ifother selection conditions are satisfied and the exclusion criteria are not met

13. no limitation according to the size and number of tumors in the liver.

Exclusion Criteria:

Patients with HCC meeting all of following criteria;

1. previous history of systemic treatment for HCC (If systemic treatment for HCC hasbeen performed at least once, it will not be enrolled in this study.) However,registration is permitted if the previous systemic treatment is for adjuvantpurposes or treatment for other cancers. Also allowed if previous HCC treatment islocal treatment. However, cases with a history of previous upper abdominalradiotherapy (including proton therapy and heavy particle therapy) are excluded.

2. any type of anticancer agent (including investigational) within 2 weeks beforeenrollment

3. Having active brain metastasis or leptomeningeal metastasis need surgery or steroidtherapy

4. Moderate to severe or intractable ascites

5. A history or presence of hepatic encephalopathy

6. Presence of active bacterial infection

7. Untreated active chronic hepatitis B or active hepatitis C

8. History of portal hypertension with bleeding within the past 6 months

9. Prior liver transplant

10. Uncontrolled severe medical comorbidity

11. unhealed wound

12. uncontrolled electrolyte imbalance

13. Non-interruptible therapeutic use of anticoagulants or thrombolytics

14. History of uncontrolled or autoimmune disease, or immunocompromised

15. interstitial lung disease

16. Other malignant disease (a history of treated malignancy -other than HCC- isallowable if the patient's malignancy has been in complete remission, offchemotherapy and without additional surgical intervention, during the preceding twoyears)

17. Mentally retarded/medically incapable of consent