This single center, open-label, uncontrolled, non-randomized observational study in patients with advanced HCC. The patients qualify either to a local treatment with transarterial chemoembolization (TACE) or to a systemic treatment with the multikinase inhibitor sorafenib. The aim of this feasibility study is to get a comprehensive image and molecular fingerprint of individual tumors, with the intention to govern therapy decisions. Furthermore, to improve the care of patients that get progressive disease under treatment, the investigators have to improve the investigators understanding of the development of therapy resistance, which will improve patient care at the time point of progressive disease. Therefore, the data of 20 patients in each group will be used to identify molecular and / or image patterns, that can be used to predict treatment responses and thus govern an optimized individual cancer treatment for patients with advanced HCC.

A single-center, open-label, uncontrolled, non-randomized clinical trial. The two treatment groups to receive:

Group A Transarterial Chemoembolization (TACE): 20 patients that are treated with TACE will get an image and molecular fingerprint of the tumor prior to the first treatment with TACE, a second image fingerprint between week 2 - 4 after the first treatment with TACE, and a third image and molecular fingerprint at the time point of progressive disease.

Group B Sorafenib: 20 patients that are treated with Sorafenib will get an image and molecular fingerprint of the tumor prior to the first treatment, between week 2 and 3 after the start of treatment and at the time point of progressive disease.

Inclusion Criteria:

All inclusion criteria must be met at the time of screening unless otherwise specified:

1. Male or female ≥ 18 years.

2. Written informed consent obtained prior to any trial specific procedure.

3. Advanced stage hepatocellular carcinoma, BCLC class B for Group A and BCLC class B or C for Group B (refer to Appendix 3 for BCLC classification).

4. Child-Pugh class A and B. Only patients with Child-Pugh index class B of not more than 7 will be included. Patients with untreatable ascites or hepatic encephalopathy > Grade 1 are excluded (see exclusion criteria; (refer to Appendix 4 for Child Pugh classification)).

5. Indication for TACE or sorafenib treatment confirmed by an interdisciplinary tumor board.

6. ECOG performance status 0, 1 or 2 (refer to Appendix 2 for definitions of ECOG grades).

7. Life expectancy of 12 weeks or more.

8. Adequate hematological parameters, as demonstrated by:

   • Hemoglobin ≥ 9.0 g/dl (SI units: 5.6 mmol/l);
   • WBC ≥ 3.0 x 109/l;
   • Absolute neutrophil count ≥1,500/mm3;
   • Platelets ≥ 75 x 109/l;
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upper limit of normal range (ULNR);
   • Bilirubin ≤ 3 mg/dl;
   • Serum creatinine ≤ 1.5 mg/dl (SI units: 132 µmol/l);
   • Prothrombin Time (PT) International Normalized Ratio (INR) ≤ 1,5;
   • Serum potassium, magnesium and calcium within normal range.

9. Safe contraception in females of childbearing potential during the entire study using an established treatment with hormonal contraceptives for at least 2 months prior to start of screening.

10. For females of child bearing potential (without using hormonal contraceptives for at least 2 months prior to start of screening) a double contraception method is requested during the entire study meeting the criteria for an effective method of birth control. That means at least two effective birth control methods such as condoms, diaphragms or intra-uterine devices must be used.

11. Male patients with partners of child bearing potential are requested to use barrier contraception in addition to having their partner use another method of contraception during the trial and for 3 months after the last dose. Male patients will also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms.

12. Able to comply with all the requirements of the protocol.

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for study participation:

1. Renal failure requiring hemo- or peritoneal dialysis.
2. Known central nervous system (CNS) tumors including symptomatic brain metastasis.
3. Patients with no adequate treatment for gastrointestinal bleeding and esophagus varices within 14 days prior to study entry.
4. Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy > Grade I (see Child-Pugh index, Appendix 4).
5. History and current cardiovascular complications, including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, a condition requiring anti arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
6. Current evidence of any severe internal, psychiatric or neurologic disease.
7. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
8. Pregnant or breastfeeding women.
9. Active alcohol and/or drug abuse.

Patients aged ≥ 18, of both genders, with advanced stage hepatocellular carcinoma, for Group A BCLC class B (intermediate stage, performance status-ECOG 0, multinodular HCC), for Group B BCLC class B or C (advanced stage, performance status-ECOG 1-2, invasive tumor pattern (vascular invasion/extra hepatic spread)).

Number: Up to 20 patients to receive therapy with TACE (Group A) and up to 20 patients to receive Sorafenib as first-line systemic therapy (Group B).