Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Recurrent Small Hepatocellular Carcinoma: a Randomized, Open-label, Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- Local progression-free survival (LPFS)
研究概览
简要总结
Recurrence rate of hepatocellular carcinoma (HCC)after resection is as high as 65.0%-83.7%.The recurrence of HCC is the most important factor affecting prognosis. Reasonable and effective treatment of recurrent lesion can significantly improve the long-term treatment efficacy of HCC. The recurrent lesion is usually detected when it's small and is the best indication for local treatment. Local ablation therapy represented by radiofrequency ablation (RFA) is one of the main treatments for recurrent small HCC. Our previous study showed that for recurrent small HCC(≤5cm), RFA has the efficacy equivalent to re-excision, with the advantages of small trauma, quick recovery, low cost, and high quality of life. With the advancement of radiotherapy equipment and the development of precise radiotherapy technology, stereotactic radiotherapy (SBRT) has become one of the routine treatments for HCC, especially for small HCC. Retrospective controlled studies have shown that SBRT is similar to RFA in treating small HCC, and the local control rate may be better than RFA. This project is to conduct a prospective, open, randomized, controlled clinical study of RFA versus SBRT for the treatment of recurrent small hepatocellular carcinoma (single lesion ≤ 5 cm, without extra-hepatic metastasis or vascular invasion). The primary endpoint is local progression-free survival (LPFS), and secondary endpoints are progression-free survival (PFS), overall survival (OS), local control rate (LCR), and safety. Data analysis will be performed according to intention-to-treat (ITT) principles. Subgroup analyses will be conducted according to the predefined stratification factor (tumor diameter ≤ 2 cm vs. 2-5 cm) and other baseline characteristics. The results of these study will help to further improve the long-term treatment efficacy of HCC and establish a rational and effective treatment model for HCC.
详细描述
Recurrence rate of hepatocellular carcinoma (HCC)after resection is as high as 65.0%-83.7%.The recurrence of HCC is the most important factor affecting prognosis. Reasonable and effective treatment of recurrent lesion can significantly improve the long-term treatment efficacy of HCC. Resection is the preferred treatment for recurrent HCC. Although liver surgery has been progressing in recent years, the alteration of anatomical structure after the first operation, the reduction of liver volume, and the mostly multi-centered origin recurrent lesions, lead to low surgical resection rate, difficult operation, high risk, multiple complications, and high recurrence rate of resection surgery. Salvage liver transplantation is difficult to apply widely due to donor shortages and other problems.
Local ablation, represented by radiofrequency ablation (RFA), is the third major treatment for liver cancer after surgical resection and transcatheter arterial chemoembolization (TACE). Many studies， by us and domestic and foreign scholars， have shown that the long-term efficacy of RFA in the treatment of small HCC is close to that of surgical resection, with a 5-year survival rate of 50%-60%. Therefore，RFA has been recommended as a frontline treatment for small HCC by many international guidelines. The recurrent lesion is usually detected when it's small and is the best indication for RFA. Our previous study showed that for recurrent small HCC(≤5cm), RFA has the efficacy equivalent to re-excision, with the advantages of small trauma, quick recovery, low cost, and high quality of life.
With the development of radiotherapy equipment and the precision imaging technology, especially the emergence of stereotactic radiotherapy (SBRT), the status of radiotherapy in the treatment of HCC is increasing. SBRT is defined as the use of external irradiation technology, which is divided into several fractions, and the high dose of radiotherapy is accurately delivered into the tumor. As a result, tumor is subjected to high dose and the normal tissue around the tumor is exposed to relatively low dose. Compared with conventional fractionated radiotherapy (CRT), SBRT possessed fewer segmentation times (1 to 6 F), higher fractional doses (5 to 20 Gy), and steeper gradients at the edge of the target region, so it has stronger biological effect. Meanwhile, SBRT can also protect the normal organs better, especially for the radiotherapy of smaller tumors. Multiple clinical studies and meta-analyses have shown that SBRT is superior to traditional CRT in the treatment of HCC, and the side effects are lower in the acute phase. SBRT has become a mainstream technology for HCC, and has been recommended as a routine local treatment for HCC by National Comprehensive Cancer Network (NCCN) guidelines and NCI radiotherapy guidelines.
Both RFA and SBRT have been recommended by the NCCN guidelines as a routine local treatment for liver cancer. They are also widely used in the treatment of liver cancer, and their therapeutic efficacy and safety have been widely approved. However, which treatment of recurrent small HCC is superior is still unknown.This project is to conduct a prospective, open, randomized, controlled clinical study of RFA versus SBRT for the treatment of recurrent small HCC (single lesion ≤ 5 cm, without extra-hepatic metastasis or vascular invasion). The primary endpoint is local progression-free survival (LPFS), and secondary endpoints are progression-free survival (PFS), overall survival (OS), local control rate (LCR), and safety. Data analysis will be performed according to intention-to-treat (ITT) principles. Subgroup analyses will be conducted according to the predefined stratification factor (tumor diameter ≤ 2 cm vs. 2-5 cm) and other baseline characteristics. The results of these study will help to further improve the long-term treatment efficacy of HCC and establish a rational and effective treatment model for HCC.
Patients enrolled in this clinical trail received either SBRT or RFA depending on the randomization allocation. Eligible subjects are stratified by maximum tumor diameter (≤ 2 cm vs. 2-5 cm) and randomly assigned in a 1:1 ratio to receive either SBRT or RFA using a computer-generated random assignment system.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-75 years;
- •Diagnosed with HCC: The diagnosis of HCC will be confirmed according to the " Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition) " formulated by the National Health Commission of China and the Barcelona Clinic Liver Cancer (BCLC) strategy for prognosis prediction and treatment recommendation of the European Association for the Study of the Liver (EASL);
- •Recurrent small HCC: Single hepatocellular carcinoma ≤ 5 cm that recurs after previous curative resection or thermal ablation, with the recurrence time ≥ 3 months from resection/ablation, and without extrahepatic metastasis or vascular invasion at recurrence;
- •No contraindications for RFA and SBRT treatment;
- •Karnofsky performance score (KPS) ≥ 90;
- •Liver function Child-Pugh class A;
- •Normal liver volume greater than 800 cm3;
- •Expected survival time longer than 6 months;
- •The function of important organs meets the following requirements: a. white blood cell ≥ 3×109/L; b. hemoglobin ≥ 80 g/L; c. platelets ≥ 50×109/L; d. blood creatinine ≤ 1.5 times the upper limit; e. prothrombin time (PT) ≤ 3 seconds above control;
- •Subject has signed the informed consent form and agreed to the treatment and follow-up schedules according to this protocol;
- •Subject must have the ability to understand and voluntarily sign the written informed consent form prior to starting any specific procedure in the study.
排除标准
- •Presence of extrahepatic metastasis or intrahepatic vascular invasion;
- •More than one recurrent lesion, or maximum diameter > 5 cm;
- •Concomitant severe cardiac, pulmonary, renal, or other major organ dysfunction, severe infection or other comorbidities, unable to tolerate treatment;
- •History of other malignancies;
- •History of allergic reactions to relevant drugs;
- •History of organ transplantation;
- •During pregnancy or lactation;
- •Unable to undergo one of the treatments (RFA or SBRT);
- •Concomitantly receiving other anti-tumor therapy (including immunotherapy and targeted therapy);
- •Other factors that may affect patient enrollment and evaluation results;
- •Refusal to comply with the study protocol requirements for follow-up and refusal to sign the informed consent form.
结局指标
主要结局
Local progression-free survival (LPFS)
时间窗: From date of randomization until the date of first documented local tumor progression or date of death from any cause, whichever came first, assessed up to 2 years.
LPFS is defined as the time from randomization to local tumor progression or death from any cause. Local tumor progression was defined as progressive disease occurring within 1 cm of the margin of the ablation region or within 1 cm of the margin of the PTV for SBRT.
次要结局
- Progression-free survival (PFS)(From date of randomization until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed up to 2 years.)
- Safety and adverse events(Acute complications are defined as adverse events occurring within 90 days after treatment; late complications are defined as adverse events occurring after 90 days of treatment completion.)
- 1-,2-,and 3-year local control rate (LCR)(1, 2, or 3 years after treatment completion.)
- Overall survival (OS)(From date of randomization until the date of death from any cause, assessed up to 2 years.)
研究者
Chen Min-Shan
Clinical Pro.
Sun Yat-sen University