Please select the eligibility criteria that correspond to the clinical trial below.
Title: Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of HCC: A Multicenter Randomized Controlled Trial (TRACE Trial)
Brief Summary: Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. In only 10% - 15% of all patients with HCC, tumors are considered resectable at presentation. In contrast to metastatic liver disease, there is no role for systemic chemotherapy in the treatment of HCC. Today only evidence is available for Sorafenib, a tyrosine kinase inhibiting agent. The arsenal of non-surgical therapies can roughly be divided into local ablative, transarterial and systemic therapies. In well selected patients, local ablative therapy can offer favorable long term results.

For patients with disease confined to the liver, but locally more advanced, transarterial treatment modalities are proposed. These therapies exploit the dual blood supply to the liver. HCC derives its blood supply almost entirely from the hepatic artery, while liver parenchyma derives \> 75% of its blood supply from the portal vein. Antitumoral agents, such as cytotoxic drugs or radionuclides, can be delivered in close proximity of the tumor.

Examples of transarterial therapies are: transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial chemoembolization with drug eluting beads (TACE-DEB) and transarterial radioembolization with Iodine-131 or Yttrium-90.

TACE is currently the gold standard for treatment of patients with intermediate stage HCC, with a reported median survival of around 17 months. A novel development in the TACE treatment for HCC is the drug-eluting bead (DEB). Recently performed small clinical trials reported the efficacy of DEBs in the treatment of intermediate stage HCC, which is substantially higher compared to conventional TACE.

Yttrium-90 radioembolization (90Y-RE) is a relatively recently developed technique which implements transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor.

In this study the investigators want to prospectively compare TACE-DEB and 90Y-RE, two novel treatments that both have theoretical and/or proven advantages compared to the use of conventional TACE, in patients with intermediate stage HCC.


Options:
A: Inclusion Criteria:

* Unresectable, multinodular asymptomatic tumor without vascular invasion or extrahepatic spread
* Confirmed Diagnosis of HCC:
* Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria
* HCC can be defined in cirrhotic subjects by one imaging technique (Computed tomography \[CT\] scan, Magnetic resonance imaging \[MRI\], or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter.
* Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria.
* Non-cirrhotic subjects:

For subjects without cirrhosis, histological or cytological confirmation is mandatory

* Documentation of original biopsy for diagnosis is acceptable
* Child Pugh class A without ascites
* Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization:

Exclusion Criteria:

* Patients on a liver transplantation list or with advanced liver disease as defined below:
* Child Pugh B and C
* Active gastrointestinal bleeding
* Encephalopathy
* Ascites
* Lesions having previously been treated with local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or cryoablation can not be selected as the target lesions.
B: Inclusion Criteria:

Eligibility criteria were:

1. Not indicated for resection,
2. Liver function of Child-Pugh class A or B,
3. 3 or fewer lesion, each 3 cm greater and 7.5 cm less in greatest diameter,
4. No portal vein involvement or extrahepatic metastasis,
5. Lesions located at least 5mm away from the hepatic hilum or gall bladder and the common bile duct,
6. Platelet count≥6.0×103/mm3 and the prothrombin activity≥60%, and
7. No previous HCC treatment.

Exclusion Criteria:

Exclusion criteria were:

1. Encephalopathy,
2. Refractory ascites,
3. Active gastrointestinal bleeding,
4. Renal failure.
C: Inclusion Criteria:

* Ages eligible for study: 18 years and above, Genders eligible for study: both
* Patients who have a life expectancy of at least 12 weeks
* Patients with histologically or cytologically documented Hepatocellular Carcinoma (HCC)
* Patients must have at least one tumor lesion that meets both of the following criteria: (1) Accurately measured in at least one dimension according to RECIST (Response Evaluation Criteria in Solid Tumors) (2) Not previously treated with local therapy
* Patients who have an ECOG (Eastern Cooperative Oncology Group) PS (Performance Status) of 0, 1, or 2

Exclusion Criteria:

* Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: "flat tumor"\] \& T1 \[Tumor invades subepithelial connective tissue\]). Any cancer curatively treated \> 3 years prior to entry is permitted
* Renal failure requiring hemo- or peritoneal dialysis
* History of cardiac disease
* Active clinically serious infections
* Known history of human immunodeficiency virus (HIV) infection
* Known central nervous system tumors including metastatic brain disease
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
D: Inclusion Criteria:

* Written informed consent.
* The diagnosis HCC is confirmed by typical appearance on imaging or cytohistological evaluation (liver biopsy).
* Accurate staging:

MRI of the liver CT-scan of the abdomen and thorax bone scintigraphy, only in case of clinical symptoms suggestive of skeletal metastases.

Exclusion Criteria:

* Hypersensitivity to doxorubicin
* Pregnancy or breastfeeding
* Age under 18 years
* Child-Pugh score \>B7
* ECOG performance status (PST) \> 1
* Bilirubin \> 2.6 mg/dl
* AST/ALT \>5x upper limit of normal (ULN)
* \>50% of liver involvement
* Main portal vein (right, left or common trunk) thrombosis
* Extra-hepatic disease
* Previous treatment of study target lesions
* 99mTc-labelled macroaggregated albumin (99mTc-MAA) scintigraphy shows lack of MAA uptake in tumor (photopenic lesion)
* Activity \> 610 MBq and activity reduction would imply a liver target dose \> 80 Gy
* patients who are declared incompetent or suffering from physic disorders that make a comprehensive judgement impossible, such as psychosis.
* Unmanageable intolerance for contrast medium
* Life expectancy \< 3 months or otherwise impossible follow-up
* Inadequate bone marrow, liver and/or renal function
* other contraindications to hepatic embolization procedures.

Answer: D