Transarterial Chemoembolization (TACE) and Stereotactic Body Radiation (SBRT) in Patients With Hepatocellular Carcinoma (HCC) Prior to Liver Transplantation (TREASURE-Tx)

Inclusion Criteria:

1. Written informed consent obtained from the subject prior to performing any protocol related procedures, including screening evaluations.

2. Age ≥ 18 years at time of study entry.

3. HCC diagnosed by histopathology and/or according to EASL or AASLD criteria at an early stage (BCLC A or UNOS T2), without any curative treatment option (resection or ablation) other than liver transplantation as determined by tumor board decision of at least one tumor lesion. Guidance: Patients with prior HCC who had surgery or locoregional treatment and had a complete remission for over 2 years and develop denovo HCC at a location different from previously treated HCC lesion(s) are eligible to participate.

4. Patients planned for liver transplantation after discussion within a multidisciplinary board.

5. Patients eligible to receive a matchReMELD-Na (SE-ReMELD-Na) - Score for hepatocellular carcinoma according to German transplant regulations. Guidance: All listing assessments must be completed before first on-study radiologic tumor assessment (first radiologic tumor assessment in treatment follow-up).

6. Treatment of all lesions by SBRT is feasible as determined by the local physician. The central review board recommendation process has been initiated (i.e. image upload by site).

7. At least one measurable site of disease with spiral CT scan or MRI according to mRECIST for HCC.

8. Sufficient liver function (< Child Pugh B8)

9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

10. Adequate blood count, liver enzymes and renal function:

    1. Hemoglobin ≥ 7 g/dL, absolute neutrophil count ≥ 1000 /µL, platelets ≥ 35000/µL
    2. Total bilirubin and serum albumin as part of Child Pugh requirement
    3. ALAT and ASAT ≤5 x ULN

11. Patients with active HIV Infection must show a CD4 cell count above 200/µL and no detectable HIV RNA for at least three months prior to the study

12. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 14 days prior to start of the study (randomization).

13. Patients of childbearing potential who are sexually active must use an adequate contraceptive method with a failure rate less than 1 % per year. Enrolled patients must agree to use adequate contraception for the duration of study treatment and up to 6 months after the end of the treatment (depending on treatment received), manufactures recommendation (TACE) and local guidelines.

14. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study.
2. Prior local tumor specific treatment of the same tumor nodule within the last 24 months.
3. Histological proven fibrolamellar HCC or mixed HCC/cholangiocarcinoma.
4. Other invasive malignancies within the past 2 years (except for non-melanoma skin cancer or non-invasive bladder cancer).
5. Impaired liver function Child-Pugh Class B > 7.
6. Ongoing or active systemic infection or psychiatric illness/social situations that would limit compliance with study requirements. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
7. Dementia or significantly altered mental status that would prohibit the understanding or rendering of information, consent, and compliance with the requirements of the protocol.
8. Pregnancy and breastfeeding. Should a patient become pregnant, the treating physician has to be informed immediately.
9. Any condition, comorbidity or circumstance that, in the opinion of the investigator, would interfere with evaluation of study treatment or affect patient safety or study results.
10. Weight less than or equal to 30 kg.
11. Prior radiotherapy to the upper abdomen