Stereotactic Radiotherapy (SRT) Liver (COLD 1)

Recruitment & Eligibility

Inclusion Criteria

Primary hepatobiliary confirmed pathologically or via imaging
Liver metastases from colorectal cancer or other solid malignancy, confirmed pathologically
New radiographic liver lesions most consistent with metastases, in a patient with previously pathologically proven solid malignancy and a previously negative liver contrast CT or MRI
The tumor must be unresectable or the patient must be medically inoperable or extra-hepatic metastases must be present
Karnofsky performance status (KPS) > 60
Age > 18 years
Patients must have recovered from the effects of previous surgery, radiotherapy or chemotherapy
Chemotherapy must be completed at least 2 weeks prior to radiation therapy or not planned to be administered for at least 2 weeks
Adequate organ function as assessed as follows:Hemoglobin > 90 g/L, Absolute neutrophil count > 1.5 bil/L, Platelets > 80,000 bil/L, Bilirubin < 3.0 times upper range of normal, INR < 1.3 or correctable with vitamin K, AST or ALT < 6.0 times upper range of normal, Creatinine < 200 umol/L (other than patients who are having dialysis or already have dialysis lines in place for future dialysis for renal failure. These patients may be treated on study with no upper limit on their creatinine.)
Child A liver score
Previous liver resection or ablative therapy is permitted.
Life expectancy > 3 months
Multiple metastases are permitted (volume of uninvolved must be at least 800 cc, and the maximal effective liver volume that may be treated is 80%.
Informed consent form

Exclusion Criteria

Patients with active hepatitis or clinically significant liver failure
Prior radiation therapy to the right upper abdomen, precluding re-irradiation of the liver. (Prior pelvic radiation is permitted, as long as no overlap between pelvic and liver radiation fields occurs.)
Prior uncontrolled, life threatening malignancy within the past year.
Gross (clinically apparent) ascites.
Pregnancy is not permitted, and in women of child bearing age, a pregnancy test and birth control are warranted.

Study & Design

Arm && Interventions

Group	Intervention	Description
Stereotactic RT or highly conformal RT	Stereotactic radiotherapy (SRT) or highly conformal (CRT)	-

Primary Outcome Measures

Name	Time	Method
Phase I: To evaluate feasibility and maximally tolerated dose of SRT	assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years
Phase II: To determine with more confidence the rate and spectrum of all toxicities that occur at the maximally tolerated dose of radiation.	assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years

Secondary Outcome Measures

Name	Time	Method
To evaluate changes in liver function following SRT.	3 to 12 months
To evaluate local control, progression-free survival and survival of patients with unresectable primary hepatobiliary cancer and metastatic liver cancer treated with SRT.	assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years
To evaluate the quality of life.	assessment: pre-treatement, 1, 3, 6,12 months post
To evaluate patterns of breathing at and during RT.	during radiation treatment only
To develop more confidence in a revised normal tissue complication probability (NTCP) model for radiation induced liver toxicity and collect preliminary data to determine how the liver responds to radiation.	at 3 months post RT
To determine whether serum cytokines and P-III-P can help predict RILD.	baseline, during radiation and up to 3 months post radiation

Recruitment & Eligibility