Adjuvant Stereotactic Body Radiation Therapy After Trans-arterial Chemoembolization in Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The study investigates the adjuvant SBRT following TACE in early and intermediate stages HCC not amenable for surgical resection or orthotopic liver transplant.

Official Title
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Adjuvant Stereotactic Body Radiation Therapy After Trans-arterial Chemoembolization in Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma Non-resectable

Intervention / Treatment
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* Procedure: TACE
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC (diagnosis: histological or radiological) Age: 18-80 Number of lesions 1-3 lesions Size of the lesion (or sum of 2-3 lesions) ≥ 4 cm Sufficient non-tumorous liver volume (≥ 800 cm3) Child Pugh Score: A5-6 or B7 BCLC A or B Patient is illegible or refused surgical resection or orthotopic liver transplant Blood work (within 2 weeks before registration): Absolute neutrophil count (ANC) ≥ 1,500 cells/mm³) Platelets ≥50,000 cells/mm³ AST (and ALT) < 5 times ULN Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min Exclusion Criteria: Evidence of extrahepatic disease (lymph node or distant metastases) Evidence of macroscopic vascular invasion Evidence of an arterio-portal or arterio-venous fistulas History of previous malignancy Active hepatitis B Previous SIRT Previous Sorafenib in the last 8 weeks Pregnant and lactating females

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE+SBRT.<br>If a patient is eligible to participate in the project according to the in- and exclusion criteria, the patient will assigned to 1-2 sessions of TACE followed by SBRT within one month from last TACE session . | Procedure: TACE<br>* 1-2 session TACE before SBRT according to the preference of the interventional radiologist. Goal of TACE is the complete emnbolization of the HCC-nodules. It is allowed to use both conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) according to the interventional radiologist preference.<br>Radiation: SBRT<br>* SBRT should be 1 month after last TACE. This can be extended till 2 months if indicated. However, prolongation of the gap between TACE and SBRT is not encouraged. Treatment center should choose one of fractionation schedule mentioned allowed in the study, in order to achieve a balance between dose applied for tumor control and constraints for OAR PTV Dose in 5 / 8 fractions (Gy) BED (α/β 10Gy) 5x 10 Gy @ 83% isodose = 50 Gy (100 Gy) 8 x 7.5 Gy @ 83% isodose = 60 Gy (105 Gy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year local control rate | After one year from the treatment, the precentage with alive subjects with no signs of local progression (the irradiated lesion). Local progression defined as more than 20% increase in diameter of enhancing tumor on contrast-enhanced CT scan in arterial phase or a new tumor mass within the original tumor volume according to modified RECIST criteria (mRECIST) | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualtiy of life based on EORTC QLQC30 | alive subjects will fill quality of life questionnaires (EORTC QLQC30) before the treatment and after 3,6 and 12 months after. The results before and after the treatment will be presented in comaprsion to the reference data. | 12 Months | 
| 1- year progression free survival | After one year from the end of the treatment, the percentage of alive subjects without the apperance of new hepatic and/or extra-heaptic new lesions outside the SBRT-field. This will be measured using contrast-enhanced CT scan Liver/Abdomen and Thorax | 12 Months | 
| Quality of life based on EORTC QLQ-HCC18 | alive subjects will fill quality of life questionnaires (EORTC QLQ-HCC18) before the treatment and after 3,6 and 12 months after. The results before and after the treatment will be presented in comaprsion to the reference data. | 12 Months |