SBRT + TACE for Primary Hepatocellular Carcinoma

Patients who are poor surgical candidates could potentially benefit from non-surgical
alternatives such as stereotactic body radiation therapy (SBRT). SBRT is an ideal approach
to minimize radiation exposure to the normal liver while maximizing the dose to the tumor.
Transarterial chemoembolization (TACE) is the combined use of intra-arterial chemotherapy
and particulate arterial embolization. This technique is typically used to make unresectable
liver lesions amenable to resection, for palliation in cases of extra-hepatic spread or
recurrence, or for symptomatic relief. The combination of intraarterial chemotherapy with
vessel embolization makes logical sense since primary and secondary liver tumors derive up
to 95% of their blood supply from the hepatic artery, while the normal liver gains the
majority of its blood supply from the portal system. Thus, using transarterial
chemoembolization it is possible to achieve high intratumor drug concentrations followed by
local ischemia, allowing uninvolved liver to be spared. This study is to determine that
these standard of care therapies combined to improve the quality of life for the patient
population.

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age

2. A life expectancy of at least 12 weeks with a Karnofsky performance status of at
least 70 (Appendix III)

3. HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria. All of the
following criteria must be met or a biopsy is required: • Known cirrhosis or chronic
HBV or HCV infection, • Hypervascular liver masses >2 cm, and either serum AFP > 400
ng/ml, or • AFP >three times normal and doubling in value in the antecedent 3 months.

4. The target lesion(s) can be accurately measured in at least one dimension according
to RECIST and must have a combined maximum tumor volume of ≤ 180 cm3.

5. No prior radiotherapy to the liver.

6. Previous systemic chemotherapy or non-radiation local therapy (such as surgery,
hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous
ethanol injection or cryoablation) is allowed. The lesion must however have shown
criteria of progression based on RECIST. Local therapy must be completed at least 4
weeks prior to the baseline scan.

7. Cirrhotic status of Child-Pugh class A or B (Appendix I)

8. Patient's lesions are deemed unresectable.

9. Patient's tumor burden or medical comorbidities disqualify them for transplant OR the
patient qualifies for transplant but refuses the operation OR patients planned for
TACE as a bridge to transplant operation.

10. Platelet count ≥ 60 x 109/L, Hemoglobin ≥ 8.5 g/dL, WBC ≥ 2000/μL International
normalized ratio (INR) ≤ 1.5 or a PT/PTT within normal limits. Patients who are being
therapeutically anticoagulated with an agent such as Coumadin or heparin will be
allowed to participate provided that no prior evidence of underlying abnormality in
these parameters exists.

11. Other baseline labs must meet the following criteria: total bilirubin <3mg/dl,
albumin>2.5mg/dl, and liver enzymes less than three times the upper limit of normal.
Creatinine must also be <1.8mg/dl or a creatinine clearance >50ml/min.

12. Must be aware of the neoplastic nature of his/her disease and willingly provide
written, informed consent after being informed of the procedure to be followed, the
nature of the therapy, alternatives, potential benefits, side-effects, risks and
discomforts.

Exclusion Criteria:

1. Renal failure requiring hemo- or peritoneal dialysis

2. Uncontrolled inter-current illness (except Hepatitis) including, but not limited to
ongoing or active infection (> grade 2 National Cancer Institute [NCI]-Common
Terminology Criteria for Adverse Events [CTCAE] version 3.0), congestive heart
failure (> New York Heart Association (NYHA) class 2), active coronary artery disease
(CAD), cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers
or digoxin), uncontrolled hypertension and any condition which could jeopardize the
safety of the patient and his/her compliance in the study . Myocardial infarction
more than 6 months prior to study entry is permitted.

3. A history of variceal bleeding where the varices have not been eradicated or
decompressed by shunt placement.

4. History of an active connective tissue disorder.

5. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

6. Pregnant or breast-feeding patients are excluded from this study because abdominal
radiation therapy has potential for teratogenic and/or abortifacient effects.

7. Total portal vein occlusion.

8. Extensive liver tumor burden, defined as more than 75% of the liver.

9. Previous or current malignancies of other histologies within the last 5 years, with
the exception of cervical carcinoma in situ and adequately treated basal cell or
squamous cell carcinoma of the skin.

10. Patients with uncontrolled distant disease will be excluded from this protocol. Those
with controlled systemic disease will still be eligible.