Hypofractionated Proton Beam Radiotherapy for Hepatocellular Carcinoma

This phase II study is to evaluate the effectiveness of hypofractionated proton beam therapy (PBT) for HCC patients in hepatitis B endemic area.

The primary endpoint is local progression free survival. The trial is a single arm phase II trial with the historical arm. The expected 3-year local progression free survival for patient with HCC patients treated with proton beam therapy would be 80%. With a power of 80% and a type I error level of 10%, evaluable 40 patients are required to reject that the null hypothesis that true 3-year local progression free survival rate is ≤65%. Considering the 10% unevaluable patients due to loss of follow up, a total 45 eligible patients for each arms will be enrolled.

Inclusion Criteria:

• HCC 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
• HCC patients who were not prospective suitable or refused for any other treatment, such as surgery or local ablation therapy, or recurrent or residual tumor after other treatments.
• without evidence of extrahepatic metastasis
• All target tumors must be encompassable within single irradiation field (15x15 cm maximum)
• 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 2 on the Eastern Cooperative Oncology Group (ECOG) score
• WBC count ≥ 2,000/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 25,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit of normal; no ascites)
• no serious comorbidities other than liver cirrhosis
• written informed consent

Exclusion Criteria:

• evidence of extrahepatic metastasis
• age < 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 3 to 4 on the Eastern Cooperative Oncology Group (ECOG) score
• multicentric HCCs, except for those with the following two conditions: *multinodular aggregating HCC that could be encompassed by single clinical target volume and within single irradiation field (15x15 cm maximum) *lesions other than targeted tumor that were judged as controlled with prior surgery and/or local ablation therapy.