Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Korea Cancer Center Hospital74 enrolled

Overview

The standard treatment for hepatocellular carcinoma (HCC) is surgery, such as, by hepatic resection or liver transplantation, but less than 20% of HCC patients are suitable for surgery. In the remaining patients with inoperable and advanced HCC, trans-arterial chemo-embolization (TACE) has been widely used but TACE alone rarely produces complete response and commonly develops recurrence. Recently several small studies reported high tumor response and local control rate after stereotactic body radiotherapy (SBRT) alone or with TACE for inoperable HCC. A single institution phase II trial with SBRT for inoperable HCC after incomplete TACE at Korea Cancer Center Hospital showed promising results: the overall response rate of 73% and 2-year local control rate of 95%. They reported severe gastrointestinal toxicity of 11% because there was no normal tissue constraint for gastrointestinal tract and dosage to gastrointestinal tract was restricted to the lowest levels possible. In addition, they found that the presence of gastroduodenal ulcer before SBRT was significantly influenced on severe gastrointestinal toxicity. Based on this study, we will conduct a multicenter phase II trial on maintenance of treatment results and reduction of severe treatment related toxicity below 5%. To achieve this, we strictly apply normal tissue constraints. Secondly, we will do Esophagogastroduodenoscopy (EGD) before SBRT to evaluate gastroduodenal ulcer. After then, we will apply the normal tissue constraint of gastrointestinal tract according to gastroduodenal ulcer.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatocellular Carcinoma

Interventions

Stereotactic body radiotherapyRADIATION

Total stereotactic Body radiotherapy (SBRT) doses will be 60 Gy in 3 fractionations. Patients receive 3 fractionations separated by \>48 hours. At least 700 ml of normal liver (entire liver minus cumulative GTV) should not receive a total dose of \> 17 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 \> 17 Gy. In patients without gastroduodenal ulcer on Esophagogastroduodenoscopy (EGD) before SBRT, D2ml of gastrointestinal tract should not exceed 35 Gy. In patients with gastroduodenal ulcer on EGD before SBRT, D2ml of gastrointestinal tract should exceed 28 Gy. (D2ml: minimum dose to 2 ml of gastrointestinal tract)

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients ≥ 20 years of age * Initially diagnosed or recurrent hepatocellular carcinoma (HCC) * Unresectable HCC * Inaccessible to local ablative treatment * Cirrhotic status of Child Pugh class A or B7 * Eastern Cooperative Oncology Group performance status 0 or 1 * Tumor size \< 10cm * The volume of uninvolved must be at least 700 ml * Incomplete response after trans-arterial chemo-embolization of 1-5 * A single lesion or multiple lesions including portal vein tumor thrombosis included in radiation field with one or consecutive sessions of SBRT * No evidence of an uncontrolled lesion at any other site * No evidence of complications of liver cirrhosis * No evidence of uncontrolled inter-current illness * Patient or guardian must be able to provide verbal and written informed consent Exclusion Criteria: * Patient with previous history of abdominal radiation * Direct invasion to esophagus, stomach or colon by HCC

Locations (7)

Inje University Haeundae Paik Hospital

Busan, South Korea

Dongnam Institute of Radiological & Medical Sciences

Busan, South Korea

Soon Chun Hyang University Hospital Cheonan

Cheonan, South Korea

Catholic University Incheon St. Mary's Hospital

Incheon, South Korea

Inha University Hospital

Incheon, South Korea

Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences

Seoul, South Korea

Soon Chun Hyang University Hospital Seoul

Seoul, South Korea

Outcomes

Primary Outcomes

Treatment related toxicity-free survival

From the date of SBRT to the date of treatment related toxicity or last follow-up; Treatment related toxicity will be evaluated by the following criteria. 1. Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0; 2. Classic radiation induced liver disease; 3. Non-classic Classic radiation induced liver disease; 4. Worsening of Child-Turcotte-Pugh score; 5. Worsening of MELD score

Time frame: 1 year

Secondary Outcomes

Overall survival

From the date of SBRT to the date of death or last follow-up

Time frame: 2 years

Progression free survival

From the date of SBRT to the date of first failure or last follow-up

Time frame: 2 years

Intrahepatic recurrence free survival

From the date of SBRT to the date of Intrahepatic recurrence or last follow-up

Time frame: 2 years

Patterns of failure

Patterns of failure (local, intrahepatic, or systemic)

Time frame: 2 years

Systemic failure free survival

From the date of SBRT to the date of systemin failure or last follow-up

Time frame: 2 years

Local control rate

From the date of SBRT to the date of local failure or last follow-up

Time frame: 2 years