A PHASE I TRIAL OF STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH HEPATIC METASTASES
UTSW IRB# 062004-005
Principal Investigator: Robert Timmerman, MD
Coordinator: Jennifer Sheppard
Contact Number: (214) 648-5536

OBJECTIVES: Stereotactic Radiotherapy (also called radiosurgery) is the use of several x-ray beams that are focused directly at tumors while protecting the healthy tissue from radiation exposure as much as possible.  The purpose of this research is to determine the maximum dose of this type of radiotherapy that a patient can safely have when the cancer has spread from the original area to the liver. In addition, we want to learn about the side effects of this treatment when given to the liver. The effects of stereotactic radiotherapy on liver tumors will be checked by CT scans and/or MRI scans and PET scans. These scans are all ways of measuring whether the liver tumor has grown, stayed the same, or reduced in size. This research is being done because cancers that have spread to the liver are difficult to treat and may be incurable with the usual radiotherapy.  The stereotactic method of treating liver tumors may or may not be shown to be better that the treatment that is currently available.  Number of Participants:  39 (UTSW study only)

KEY INCLUSION CRITERIA:

• Histologically proven primary cancer.
• Eligible patients must have appropriate staging studies identifying them as AJCC stage IV with up to five liver metastases. Patient may have other sites of metatastic disease.
• All eligible patients must have liver metastases that are visualized on either CT scans and/or MRI of the abdomen.
• The cumulative total dose to at least 2/3 of the liver and surrounding normal tissues including esophagus, stomach, and small bowel, must not exceed 15 Gy.
• There must be no other antineoplastic treatment given concomitantly with radiotherapy.
• Patient may have previous history of systemic therapy more than 1 month prior to the start of Accuray treatment to the liver.
• If Cyberknife is chosen for treatment delivery, patients must agree to percutaneous or laparoscopic biopsy of the metastasis and placement of three to five fiducials.
• Patients must be past their 18^th birthday at the time of registration.
• The patients' Karnofsky performance status must be > 60%.
• Patients must have the following laboratory parameters: 
  * Albumin >3 g/dL
  * Alkaline Phosphatase <1.5 X Upper limits of Normal (ULN)
  * SGOT, SGPT <1.5 X ULN
  * Total Bilirubin <1.5 X ULN
  * g-GGT <1.5 X ULN
  * PT<1.5 X ULN
  * PTT <1.5 X ULN
  * a-feto protein: no specific requirement
  * Hemoglobin>10 g/dL
  * Platelets >100,000/ µm³
  * ANC >1,000/mm 
• Patients must have expected life expectancy >3 months.

• All patients must be willing and capable to provide informed consent to participate in the protocol.

• Patient unable to cooperate with requirements of the protocol.
• Patients with prior radiation to the liver or upper abdomen who, after the protocol treatment, will have cumulative dose to the liver and normal tissues greater than the constraints of the protocol.
• Prior history of diagnosed inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease.
• Patients with active peptic ulcer disease.
• Patients with hepato-renal syndrome.
• Pregnant or lactating women are ineligible. Women/men of reproductive potential may not participate unless they agree to use an effective contraceptive method such as condom/diaphragm and spermicidal foam, intrauterine device(IUD), or prescription birth control pills.
• Patients with malignant ascites.
• Patients with metastatic germ cell or hematologic malignancy to the liver.

SCHEMA
Eligible Patient (Patients with up to 5 metastatic liver tumors)
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Stereotactic Radiosurgery

Total dose is given in three fractions of stereotactic radiosurgery. Entire treatment will delivered within 12 days.
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Assess toxicity and response to treatment
determined by CT scans or MRI