Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma

Inclusion Criteria: * Hepatocellular Carcinoma diagnosed as (i) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level greater than 200 IU/ml and a radiologically compatible feature with HCC in one or more CT/MRI/angiograms, or (ii) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level less than 200 IU/ml, and a radiologically compatible feature with HCC in two or more CT/MRI/angiograms or (iii) histological confirmation * Inoperable HCC or refusal to surgery * Recurrent/residual tumor after other local treatments (local ablation therapy, or transarterial chemoemobolization, etc), or unsuitable/refusal to other treatments. * Patients without evidence of extrahepatic metastasis * The largest diameter of tumor should be less than 7cm, and the number of tumor ≤2 * The targeted tumors is more than 2cm away from the alimentary tract (i.e., stomach, duodenum, esophagus, small and large bowel) * No previous treatment to target tumors by other forms of RT * Liver function of Child-Pugh class A or B7 (Child-Pugh score of ≤7) * Age of ≥18 years * Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) score * Required Entry Laboratory Parameters WBC count ≥ 1,500/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 30,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT \< 5.0× upper limit of normal; no uncontrolled ascites * No serious comorbidities other than liver cirrhosis * Signed informed consent form prior to study entry Exclusion Criteria: * There is evidence of extrahepatic metastasis. * Age of \<18 years * Liver function of Child-Pugh class B8-9 and C (Child-Pugh score of \>7) * Previous history of other forms of RT adjacent to target tumors * Poor performance status of 2 to 4 on the Eastern Cooperative Oncology Group (ECOG) score * Multicentric HCCs, except for those with the following two conditions: (i) multinodular aggregating HCC that could be encompassed by single clinical target volume and within single clinical target volume; (ii) lesions other than targeted tumor that were judged as controlled with prior surgery and/or local ablation therapy. * Pregnant or breast feeding status * Previous history uncontrolled other malignancies within 2 years