Stereotactic Ablative Radiotherapy for Hepatocellular Carcinoma With Major Portal Vein Invasion

Study Overview
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Brief Summary
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Recently, several studies reported promising outcomes of patients after external beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis. However, conventional EBRT is composed of many fractions (20-35 fractions). On the other hand, stereotactic ablative radiotherapy is a newly emerging treatment method to deliver a high dose of radiation to the target using a few fractions with a high precision within body. SABR increases radiation biologic effect for tumor, makes patients more comfortable due to reduction of the number of hospital visit, and enables patients to receive another treatment more quickly. This study will evaluate SABR effect with 40 Gy in 4 fractions for HCC with major portal vein tumor thrombosis.

Official Title
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Multicenter Phase II Study of Stereotactic Ablative Radiotherapy for Hepatocellular Carcinoma With Major Portal Vein Invasion

Conditions
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Hepatocellular Carcinoma, Portal Vein Tumor Thrombus

Intervention / Treatment
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* Radiation: Stereotactic ablative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 20 years of age Initially diagnosed or recurrent hepatocellular carcinoma (HCC) Eastern Cooperative Oncology Group performance status 0 or 1 HCC with major portal vein tumor thrombosis (tumor thrombosis in the main portal vein or 1st branch of portal vein) Cirrhotic status of Child Pugh class A or B7 Patients can have extra-hepatic disease; provided the hepatic disease is the highest burden, the extra-hepatic disease is low burden and potentially treatable with radiotherapy, chemotherapy and target agent etc; patient survival is expected to be at least 6 months. Patient or guardian must be able to provide verbal and written informed consent Exclusion Criteria: Prior trans-arterial chemo-embolization ≥4 after diagnosis of major portal vein tumor thrombosis Severe complication caused by liver cirrhosis eg. variceal bleeding, poorly controlled ascites, hepatic encephalopathy) Uncontrolled inter-current illness except liver cirrhosis

Ages Eligible for Study
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Minimum Age: 20 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: Stereotactic ablative radiotherapy<br>Stereotactic ablative radiotherapy for HCC patients with major portal vein tumor thrombosis (tumor thrombosis in the main portal vein or 1st branch of portal vein) | Radiation: Stereotactic ablative radiotherapy<br>* The HCC patients with major portal vein tumor thrombosis (tumor thrombosis in the main portal vein or 1st branch of portal vein) will be included in this study. Total stereotactic ablative radiotherapy (SABR) doses will be 40 Gy in 4 fractionations. Patients receive 4 fractionations separated by >48 hours. At least 700 ml of normal liver (entire liver minus cumulative GTV) should not receive a total dose of > 19.2 Gy in three fractions. If volume of normal liver does not exceed 700 ml, at least 70% of normal liver should not receive a total dose of > 19.2 Gy. Dose of spinal cord do not exceed 26 Gy. Dose of esophagus, stomach and intestine do not exceed 35 Gy.<br>* Other names: Stereotactic body radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor stabilization rate | Tumor stabilization rate was based on the combined number of patients with complete response(CR), partial response(PR), and stable disease(SD) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the date of SABR to the date of death or last follow-up | 6 months, 1 year and 2 year | 
| Tumor progression free survival | From the date of SABR to the date of first failure or last follow-up | 6 months, 1 year and 2 year | 
| Treatment related toxicity | Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0; Classic radiation induced liver disease; Non-classic Classic radiation induced liver disease; Worsening of Child-Turcotte-Pugh score; Worsening of MELD score | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Stereotactic ablative radiotherapy, Stereotactic body radiotherapy, Portal vein tumor thrombus