Patients on this study will self administer Prednisone for three days before starting Radiation Therapy (RT) and continue to take 60 mg/day during the first three fractions of RT.

Inclusion Criteria:

• Patients with hepatocellular carcinoma are eligible for this trial. Hepatocellular carcinoma is defined as having at least one of the following:

  1. Biopsy proven hepatocellular carcinoma (HCC); or
  2. A discrete hepatic tumor(s) as defined by the AASLD criteria (80) - for cirrhotic patients, >1cm with arterial hypervascularity and venous or delayed phase washout on contrast enhanced CT or MRI.

• Patients must have recovered from the acute effects of prior liver-directed therapy (e.g., RT, RFA, or TACE), and a minimum of 4 weeks must have passed since the last procedure and protocol therapy.

• Patients must have a performance status of ≤2.

• Patients must be 18 years of age or older.

• Patients with at least one of the following:

  1. ALBI score equal to (-1.81) or higher (worse). This value was calculated as the equivalent ALBI score for CP score equal 7 in Cousins et al study's cohort(59).
  2. Lesion(s) with a cumulative treatment diameter of ≥ 4cm.
  3. CP score equal to 7 or higher (worse).

• Patients must understand and be willing to sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks.

Exclusion Criteria:

• Any serious disease, comorbidity or intercurrent illness which precludes delivery of radiation therapy, as determined by the treating investigator.

• Any contraindication to the administration of steroids, including

  • Documented hypersensitivity to prednisone or any component of the formulation.
  • Systemic fungal infection.
  • Patients with uncontrolled infections or with chronic infections requiring antibiotics.

Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.

• Uncontrolled hyperglycemia.

  • Patients with insulin -dependent diabetes.
  • Patients with decompensated liver disease, defined as: clinical ascites requiring paracentesis, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage.
  • Active gastrointestinal bleeding within 30 days of enrollment.