SBRT or TACE for Advanced HCC

Inclusion Criteria:

• HCC (biopsy or radiological diagnostic (>1 cm, enhancing in arterial phase andwash-out in later phases).
• Number of lesions: not more than 3 lesions
• Lesion size: up to 10 cm for a single lesion (and up to 10 cm cumulative diameter, ifthere is more than 1 lesion)
• Child-Pugh A or B (<7) on examination within 6 weeks prior to study entry
• BCLC Stage A/B
• Must be fit (eligible) for SBRT and TACE
• Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) orif these options are not available
• Distance between GTV (lesion) and luminal structures (including esophagus, stomach,duodenum, small or large bowel) is >10 mm
• All blood work obtained within 2 weeks prior to study entry with adequate organfunction defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelets ≥50,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention toachieve Hgb ≥ 8.0 g/dl is acceptable.)
• Total bilirubin < 2 mg/dL
• Prothrombin time/INR < 1.4 (unless on Coumadin/Warfarin)
• Albumin ≥ 28 g/L
• AST (and ALT) < 5 times ULN
• Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min
• Left-ventricular ejection fraction >50% (cardiac ejection fraction should bemeasured in case of history of cardio-vascular disease.
• May have had previous surgery, ethanol injection and RFA to the liver

Exclusion Criteria:

• • Not suitable for clinical trial or follow-up
• Prior invasive malignancy (except non-melanomatous skin cancer) unless diseasefree for a minimum of 2 years (Note that carcinoma in situ of the breast, oralcavity, or cervix are all permissible). No active cancer therapy.
• Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE)
• Non-enhancing HCC on CT or CT-angio or
• Portal vein thrombosis/macroscopic venous invasion
• Arterio-portal and arterio-venous fistulas observed on pre-study imaging (if itis found during the TACE, the fistula may be embolized before injection of thedrug).
• Evidence of metastatic disease including nodal or distant metastases.
• Previous TACE or radiation to the liver (including SIRT)
• Life-threatening condition (including untreated HIV and active hepatitis B/C)
• Detectable HBeAg and HBV viral load > 20,000 IU/mL or
• HBeAg-negative chronic hepatitis B and HBV viral load >2,000 IU/mL
• If HBV-DNA copy is higher than 500 copies/ml, anti-viral therapy, such asEntecavir followed by observation for 2 weeks.
• If anti-HCV antibody is positive (may be false positive) and increased HCVviral load indicating active disease. Active HCV should be treatedsufficiently before inclusion in the study. Below 2 million copies permilliliter (mL) is related to chronic hepatitis C that does not needantiviral therapy.
• Patients with active hepatitis B or C should be on treatment for at least 4weeks before inclusion in the trial
• On sorafenib or other antineoplastic drug therapy within 7 days before inclusion (not accepted until time of progression).
• Pregnancy or women of childbearing potential require a negative pregnancy testwithin 28 days