Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC

Study Overview
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Brief Summary
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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality and the sixth most prevalent cancer in the world. Standard treatments for early-stage HCCs include resection, liver transplantation, and percutaneous ablation, with 5-year survival rates of over 50 percent. Less than one-third of patients, however, are candidates for hepatic resection, and the use of radiofrequency ablation (RFA) may be significantly limited in cases with unfavorable tumor location and poor visibility on images, which increase the risk of technical failures and complications after RFA. Recent advancements in radiotherapy and imaging have made it possible to deliver optimal radiation doses on the tumor site while minimizing exposure to normal organs. Stereotactic body radiation therapy (SBRT) is a method of high-precision radiation therapy that concentrates high-dose radiation to HCC in a short period of time to maximize the therapeutic effect on the tumor and minimize the side effects on normal tissues. Prospective and retrospective studies on SBRT for HCC have demonstrated its efficacy for local tumor control in small HCC. On the basis of these promising clinical results, a number of studies have compared the efficacy of RFA and SBRT. However, there is no strong evidence from randomized controlled trials comparing SBRT and RFA. In order to evaluate and compare the local efficacy and clinical outcomes of SBRT and RFA in patients with recurrent HCC, we conduct this non-inferiority trial.

Detailed Description
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A total of 178 subjects are randomly assigned to one of two treatment groups (89 patients in the body stereotactic radiotherapy group and 89 patients in the radiofrequency ablation group). If the assigned treatment method is technically infeasible, patients are allowed to be treated with the other method. RFA: When localization of the lesion is difficult under image guidance, when it is difficult to secure a safe needle path, when there is a risk of collateral thermal damage to adjacent organs, and when it is difficult to prevent it. SBRT: When irradiation with 45 Gy (daily dose of 15 Gy) is infeasible due to the maximum tolerance dose of normal organs.

Official Title
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A Phase III Randomized Controlled Non-inferiority Trial to Compare Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Radiation: Stereotactic Body Radiotherapy
* Procedure: Radiofrequency Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient over the age of 18 primary or recurrent HCC that is not suitable for surgery HCCs with a longest diameter of ≤3cm and ≤2 lesions no evidence of intrahepatic or extrahepatic residual disease except for target lesions Child-Pugh class A or B hepatic function no macroscopic vascular invasion or extrahepatic metastasis written informed consent Exclusion Criteria: Eastern Cooperative Oncology Group performance status score 3 or 4 uncontrolled ascites, variceal bleeding, or hepatic encephalopathy previous history of liver transplantation an active gastric or duodenal ulcer within 3 months before screening pregnant woman uncontrolled other malignancies except for HCC within 2 years before screening platelet count <50,000/µl Patients who are judged by the researcher to be difficult to conduct clinical research

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RFA group<br>RFA are performed under local anesthesia or monitored anesthesia care with either a 15-gause or 17-gause internally cooled electrode, depending on the size of the tumor. RFA procedures are continued by modifying the output power based on the location and size of the tumor until the entire tumor and border area sizes of greater than 0.5 cm are included in the detected target lesion on ultrasound or CT. | Procedure: Radiofrequency Ablation<br>* - RFA are performed under local anesthesia or monitored anesthesia care with either a 15-gause or 17-gause internally cooled electrode, depending on the size of the tumor.<br>|
| Experimental: SBRT group<br>A total dose of 45 Gy is presecribed using 15 Gy per fraction over 3 consecutive days. | Radiation: Stereotactic Body Radiotherapy<br>* Verify the setup position and respiration of patients as in the simulation CT image. To precisely align the tumor prior to each treatment, cone-beam CT and gated fluoroscopy using the On-board Imager mounted on the linear accelerator are performed. The Real-time Position Management system is used to monitor the accuracy of breathing phase during treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local progression-free survival rate, per-protocol (PP) | Local progression-free survival rate, PP | At year 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate, intention-to-treat (ITT) | Progression-free survival rate, intention-to-treat (ITT) | At year 2 | 
| Overall survival rate, ITT | Overall survival rate, ITT | At year 2 | 
| Intrahepatic progression-free survival rate, PP | Intrahepatic progression-free survival rate, PP | At year 2 | 
| Intrahepatic progression-free survival rate, ITT | Intrahepatic progression-free survival rate, ITT | At year 2 | 
| Progression-free survival rate, PP | Progression-free survival rate, PP | At year 2 | 
| Progression-free survival rate, ITT | progression-free survival rate, ITT | At year 2 | 
| Adverse reaction rate, PP | Adverse reaction rate, PP | At year 2 | 
| Adverse reaction rate, ITT | adverse reaction rate, ITT | At year 2 | 
| Adverse reaction rate ≥ Gr 3, PP | Adverse reaction rate ≥ Gr 3, PP | At year 2 | 
| Adverse reaction rate ≥ Gr 3, ITT | Adverse reaction rate ≥ Gr 3, ITT | At year 2 | 
| Change of Child-Pugh score , PP | Change of Child-Pugh score , PP | At year 2 | 
| Change of Child-Pugh score, ITT | Change of Child-Pugh score, ITT | At year 2 | 
| Local progression-free survival rate according to the tumor location, PP | Local progression-free survival rate according to the tumor location, PP | At year 2 | 
| Local progression-free survival rate according to the tumor location, ITT | Local progression-free survival rate according to the tumor location, ITT | At year 2 |