A Dose Escalation Trial of Radiation Therapy (RT) for Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

* Eligible patients include those with HCC based on the diagnostic criteria of European Association for the Study of the Liver (EASL), either confirmed cyto-histologically or confirmed non-invasively (restricted to cirrhotic patients) by radiological criteria (two coincident imaging techniques and focal lesion \> 2 cm with arterial hypervascularization) or combined criteria (one imaging technique associated with AFP, focal lesion \> 2 cm with arterial hypervascularization, and AFP levels \> 400 ng/ml).
* They have Child-Pugh grade A cirrhosis and are HBsAg-positive for more than 6 months.
* These patients are not feasible for other conventional treatment modalities of treatment including surgery, transarterial embolization, ethanol injection, and radiofrequency ablation.
* No systemic anti-cancer therapy with high priority is available.
* All of the above 3 criteria should be judged by the caring physician.
* All intrahepatic disease must be encompassed within the radiation fields, except intrahepatic diseases outside the radiation field(s) have been controlled by other treatment modalities before radiotherapy.
* Karnofsky Performance Scale ≧ 80.
* Age \> 18.
* Adequate bone marrow function, defined as follows:

  * Absolute neutrophil count (ANC) \> 1,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
  * Platelets \> 20,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
  * Hemoglobin \> 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of blood transfusion or other intervention to achieve Hgb \> 8.0 g/dl is acceptable.)
* Previous liver resection, embolization, or ablative therapy is permitted.
* Chemotherapy and/or targeted agent therapy must be completed at least 2 weeks prior to radiation.
* Women of childbearing potential and male participants must practice adequate contraception.
* Patient must sign informed consent prior to study entry.
* Pretreatment evaluations for eligibility include:

  * A complete history and general physical examination
  * For women of childbearing potential, a serum or urine pregnancy test must be performed within 72 hours prior to registration INR, total bilirubin, albumin, alkaline phosphatase, AST, ALT within 1 week prior to study entry
  * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

Exclusion Criteria:

* Prior invasive malignancy, other than HCC, (except nonmelanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
* Tumor thrombosis in the main trunk of portal vein, hepatic vein, or inferior vena cava.
* Child-Pugh grade B or C cirrhosis.
* Extrahepatic metastasis.
* Clinical ascites that requires diuretic treatment or paracentesis for symptom relief.
* Serum alanine aminotransferase (ALT) level \> 5X normal upper limits or total bilirubin level \> 3.0.
* Active hepatitis (serum ALT level \> 5X normal upper limits) or clinically significant liver failure.
* Positivity of anti-HCV, pregnancy, nursing women, or women of childbearing potential, and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.