Transarterial Chemoembolization vs CyberKnife for Recurrent Hepatocellular Carcinoma

• CyberKnife (Device), also known as CK: Standard of Care
• TACE (Procedure), also known as Transcatheter arterial chemoembolization: Standard of Care
• CT Contrast (Drug), also known as contrast dye: Standard of Care
• doxorubicin (Drug), also known as Adriamycin, hydroxydaunorubicin: Standard of Care
• Epirubicin (Drug), also known as Ellence, Pharmorubicin, Epirubicin Ebewe: Standard of Care
• 5-fluorouracil (Drug), also known as 5-FU, f5U, Adrucil, Carac, Efudix, Efudex, Fluoroplex: Standard of Care
• Mitomycin C (Drug), also known as Mutamycin, MTC: Standard of Care
• Gemcitabine (Drug), also known as Gemzar: Standard of Care
• Cisplatin (Drug), also known as cisplatinum, cis-diamminedichloroplatinum(II), CDDP, Platinol, Platinol-AQ: Standard of Care
• SMANCS (Device), also known as styrene maleic acid neocarzinostatin, poppyseed oil: Standard of Care

Primary outcomes

• Freedom from local progression at 6 months and 12 months [6 months and 12 months]

Secondary outcomes

• Progression-free survival [at 6, 12 and 18 months]
• Overall survival [at 6, 12, 18 months and up to 3 years]
• Serum AFP levels [1 month, 3 months, 6 months, 12 months and 18 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Confirmed hepatocellular carcinoma by one of the following:

  * Histopathology
  * One radiographic technique that confirms a lesion >=2 cm with arterial enhancement with washout on delayed phase
* Hepatic lesion in patients for whom surgical resection is not possible or would not result in an opportunity for cure
* Radiographic evidence of persistent, progressive or recurrent disease in an area previously treated with TACE. This evaluation should be determined after 6 weeks of initial TACE
* Multi-specialty evaluation whereby the recurrent liver lesion was deemed by both the attending radiation oncologist and interventional radiologist amenable to treatment by the respective modality

  * Eligible patients must undergo an IV contrast CT scan of the liver within 6 weeks of enrollment onto the study; a contrast enhanced liver MRI may be substituted for the IV contrast CT of the liver.
  * A recent serum AFP must also be obtained within 4 weeks of enrollment.
* Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension. Multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 7.5cm as long as the dose constraints to normal tissue can be met
* Eastern Clinical Oncology Group performance status 0, 1 or 2
* Patients with liver disease classified as Child Pugh class A/B; if Child's class B, score must be 8 or less
* Albumin >= 2.5 g/dL
* Total bilirubin <= 3 mg/dL
* INR <= 1.5
* Creatinine <= 2.0 mg/dL
* Age >= 18 years old
* Life expectancy>= 6 months
* Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Prior radiation for the recurrent liver tumors
* Prior radiotherapy to the upper abdomen
* Prior RFA to index lesion
* Liver transplant
* Tumors >= 7.5 cm in greatest axial dimension
* Portal vein thrombus
* Large varices within 2 cm of index lesion (seen on cross section imaging)
* Contraindication to receiving radiotherapy
* Active gastrointestinal bleed within 2 weeks of study enrollment
* Ascites refractory to medical therapy
* Women who are pregnant
* Administration of any systemic chemotherapy within the last 1 month
* Presence of multifocal lesions located in different lobes of the liver or extrahepatic metastases
* Participation in another concurrent SYSTEMIC treatment protocol
* Prior history of malignancy other than HCC

• Albert Koong, Principal investigator, Stanford University