A Dose-finding, Safety and Preliminary Efficacy Study of Stereotactic Radiosurgery for Hepato-cellular Carcinoma and Metastatic Disease to the Liver.

Inclusion Criteria:

1. Hepatocellular carcinoma (as defined by biopsy or alpha-fetoprotein (AFP) greater
than 1000ng/dL with appropriate imaging) or liver metastases from colorectal cancer
or other tumor (as defined by biopsy or elevated CEA or a positive PET scan in
conjunction with a mass on CT or MRI in a patient with previously resected cancer).
Patients with at least one measurable liver lesion and no more than 3 are eligible if
they meet all other eligibility criteria including the dose constraints on the
composite plan.

2. ECOG performance status of 0-1.

3. Patients are not candidates for definitive surgical resection because of tumor
location, hepatic function, or other medical or personal reasons.

4. Patients with HCC who are being considered for liver transplant may be entered as a
bridge to transplant if it is considered by the transplant team that an ablative
therapy would be of value while awaiting transplant.

5. If cirrhosis is present, patients will have Child-Pugh score of A or B (see Appendix
A in the Master Protocol).

6. Patients will have tumors not optimally treated with radio-frequency ablation by
interventional radiology, or by GI/transplant surgery. This could be for reasons of
size, tumor location, or other reasons.

7. Ability to place fiducial markers in the vicinity of the tumor to allow for
radiographic tracking of respiratory motion and tumor localization. Fiducial
placement will generally be done by interventional radiology.

8. Estimates of hepatic tolerance must meet the criteria as defined in Section III. This
eligibility will not be able to made definitively until the patient has agreed to
participate. in the study and the appropriate scan analyses and dosimetry have been
performed. No more than one decrement in dose from the planned dose level will be
allowed for an individual patient because of exceeding the maximal liver doses before
the patient is declared ineligible for study.

9. Adequate bone marrow and renal function as assessed by the following:

- Absolute neutrophil count (ANC) > 1000/mm3

- Platelet count > 80,000/mm3

- Creatinine < 2.0 mg/dL OR Creatinine clearance > 45 mL/min based on
Cockcroft-Gault formula).

10. Patients with extra hepatic metastatic disease are eligible if it is the opinion of
the treating physician that local therapy to the liver may produce worthwhile
clinical benefits

11. Patient is able to understand fully the potential risks and benefits of this approach
and signs an appropriate informed consent.

12. Male and female of >18 years of age. Male or female patients capable of reproduction
must agree to use medically acceptable methods of contraception, such as an
intrauterine device, diaphragm, with spermicide, condom with spermicide or
abstinence. Inclusion of females of childbearing potential requires a negative
pregnancy test within 14 days prior to study initiation.

Exclusion Criteria:

1. Child-Pugh Class C cirrhosis

2. Patients with clinically apparent CNS disease.

3. Medical or psychiatric illness that would not allow the patient to tolerate the
proposed treatment including inability to lie flat for an extended period of time,
severe claustrophobia or other reasons.

4. Uncontrolled or significant cardiovascular disease including: myocardial infarction
within 6 months, uncontrolled angina within 6 months, Class III-IV New York Heart
Association (NYHA) congestive heart failure, grade 3 cardiac valve dysfunction

5. Evidence of decompensated liver disease as evidenced by: clinically significant
ascites refractory to diuretic therapy) evidence of hepatic encephalopathy,
coagulopathy not corrected by conservative measures.

6. A history of CTC Grade 3 bleeding esophageal or gastric varices within the past 2
months. Prior variceal bleed permitted if patient has undergone banding or
sclerotherapy and there has been no evidence of bleeding for 2 months. Patients at
risk for varices (based on the following: known history of esophageal or gastric
varices; evidence of hepatic cirrhosis and/or portal hypertension including
biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be
screened for esophageal varices. If varices are identified that require intervention
(banding), patient will not be eligible until varices adequately treated.

7. Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious disease) illness must
not be enrolled into this study.

8. Uncontrolled intercurrent illness.

9. Inability to comply with study and/or follow-up procedures.

10. A patient with Child-Pugh Class A will not be eligible for study if the liver dose
constraint described in Section 3.2 cannot be met after two decrements in dose per
fraction as described above.

11. A patient with Child-Pugh Class B will not be eligible for study if the liver dose
constraint described in Section 3.2 cannot be met after two decrements in dose per
fraction as described above.