Dose Escalation Study for Primary Hepatocellular Carcinoma

Despite recent advances in early detection and diagnosis, only 30-40% of patients with
hepatocellular carcinoma may benefit from radical therapies. Liver transplantation offers the
best chance for cure. Surgical resection has been the only other potentially curative option,
but the majority of patients are not candidates for resection. This reflects the usual
comorbidity of severe underlying liver disease that either precludes surgery or makes the
surgical approach extremely dangerous.

Inclusion Criteria:

Evaluation by the Surgery and/or Liver Transplant Team has been performed and the patient
is not considered a candidate for either "standard" therapy to target area (upper abdomen)

- Adequate liver function defined as:

- total bilirubin < 3mg/dl, albumin > 2.5 g/dl

- normal PT/PTT unless on anticoagulants

- mild elevation of liver enzymes acceptable (must be less than three times upper
limit of normal)

- Adequate renal function (creatinine < 1.8 mg/dl or creatinine clearance ≥ 50 ml/min)

- Adequate bone marrow reserve:

- ANC count ≥ 1500 mm3

- Platelets ≥ 50,000/mm3

- Hemoglobin > 9 g/dL

NOTE: Lab values must be obtained within 2 weeks prior to being registered for protocol
therapy.

Exclusion Criteria:

- No history of systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis or
scleroderma

- No chemotherapy within 14 days before radiotherapy (chemotherapy may cause transient
hepatitis with hepatomegaly)

- No subsequent chemotherapy planned within 2 weeks of radiotherapy

- No active liver infection

- No acute Hepatitis. Definition of active disease:

- Hepatitis A: Acute hepatitis determined by presence of Anti-HAV- IgM

- Hepatitis B:

1. HBsAg (HB surface Antigen): present in patients with acute and chronic
hepatitis

2. HBV DNA present in patients with active viral replication in amounts greater
than 100,000 copies

3. HBeAg is present in wild type HBV infection and suggests active replication

4. Anti-HBs: Antibody against HBsAg appears after HBV infections and confers
immunity

5. Anti-HBc-IgM: Antibody against HBcAg, fraction IgM, present in acute
infection and often could be detected during periods of high viral
replication in chronic disease

6. Anti-HBc-IgG: is present in chronic disease