The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is one of the most significant prognostic factors for poor prognosis, without treatment, their survival is less than 3 months. In the HCC patients who combined with PVTT, Radiation therapy (RT) showed 50% of local control and about 10 months survival duration. Despite the standard treatment of the HCC combined with PVTT is sorafenib, but Korean Liver Cancer Study Group (KLCSG) recommend RT as an alternative option in those patients. Investigators previously reported the retrospective study that the scheduled interval Trans-catheter Arterial Chemo-embolization (TACE) followed by RT for HCC combined with PVTT and 60% of the patients showed objective response without significant elevation of complication. However, the prospective outcomes of TACE followed by RT for HCC are scantly reported. Based on those background, we start this prospective study to evaluate the clinical outcomes and adverse event in the RT after TACE in the unresectable HCC patients who combined with PVTT.

Inclusion Criteria:

1. Patients must have a diagnosis of HCC by at least one criterion listed below (korean liver cancer study group (KLCSG) guideline 2009) 1.1 Pathologically (histologically or cytologically) proven diagnosis of HCC 1.2 Liver nodule in high risk group 1.2.1 If alpha fetoprotein (AFP) ≥200 ng/mL , ≥ 1 typical HCC enhancing pattern on dynamic contrast enhanced CT or MRI 1.2.2 If AFP<200 ng/mL, ≥2 typical HCC enhancing pattern on dynamic contrast enhanced CT, MRI, and angiography 1.3 ≥ 2 cm nodule in liver cirrhosis (LC), ≥ 1 typical HCC enhancing pattern on dynamic contrast enhanced CT or MRI

2. Patients must have a diagnosis of PVTT 2.1 Early arterial enhancement and delayed washout on multiphasic CT or MRI

3. Eastern cooperative oncology group performance status 0 1 2

4. Age ≥ 20 and 70 or less

5. Unsuitable for resection or transplant or radiofrequency ablation (RFA)

6. Unsuitable for or refractory to TACE or drug eluting beads (DEB)

7. Agreement of study-specific informed consent

8. Assessment by radiation oncologist and medical oncologist or hepatologist within 28 days prior to study entry?

9. Child-Pugh score A-B within 7 days prior to study entry

10. Normal liver (Liver minus gross tumor volume) ≥ 700 cc

11. Blood work requirements

    • Absolute neutrophil count (ANC) ≥ 1,500 /mm3, Platelet ≥ 70,000/mm3, Hgb ≥ 8 g/dl
    • Liver function test (LFT): Total bilirubin<3.0 mg/dL, International normalized ratio(INR) < 1.7, Albumin ≥ 2.8g/dL, Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT)< 6 X normal
    • Serum creatinine < 1.5 X normal, or creatinine clearance ≥ 60 mL/min

12. Male, consent contraception at least 6 months

13. Childbearing potential woman, consent contraception at least 6 months

14. Life expectancy more than 12 weeks

15. Stable breathing more than 5 minutes

Exclusion Criteria:

• 1. Complete obstruction of main portal vein 2. Pregnant and/or breastfeeding woman 3. Previous upper abdominal RT history 4. Uncontrolled active co-morbidity 5. Another primary cancer history within 2 years 6. Uncontrolled ascites or hepatic encephalopathy 7. Connective tissue disease which known as radiation hypersensitivity 8. Uncontrolled moderate to severe gastroduodenal ulcer or esophagogastric varices