hypofractionated proton beam radiotherapy for inoperable hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma

Summary: this phase ii study is to evaluate the effectiveness of hypofractionated proton beam therapy (pbt) for hepatocellular carcinoma 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 will be enrolled.

Eligibility criteria:
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