A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma

Abstract

Background: At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors. By high-frequency pulse, the tumor cell membrane can be irretrievably perforated, resulting in the destruction of the intracellular environment, which can preserve important structures in the treatment area. However, there are no randomized controlled clinical trials comparing the efficacy of IRE with traditional local ablation in the treatment of liver cancer.

Aims: This study aims to conduct a randomized controlled clinical trial comparing the efficacy of IRE with RFA in the treatment of liver cancer.

Methods: We will conduct a multicenter, randomized, parallel-controlled non-inferiority clinical trial to compare the efficacy and safety of IRE and RFA for hepatocellular carcinoma (HCC). One hundred and ninety patients with HCC from five academic medical centers will be enrolled. The patients will be randomized into treatment arm (IRE) and control arm (RFA). The primary outcome is the progress -free survival (PFS) and the key secondary outcome is the Overall survival (OS).

Results: Forty-eight patients had been recruited from 5 centers, of which, 33 patients (median age, 59.1 years) with 38 tumors had completed the 1-month follow-up and 21 patients have complete the 3-month follow up, with 2.3 months median follow up period. The mean largest tumor diameter is 3.9 cm. No end point was observed for PFS or OS in both groups, and the complete ablation rate was 100% in both groups. The lesions in the IRE group showed obvious shrinkage 1 month after procedure. One major adverse event (AE) was occurred in the control group.

Conclusion: This is the first randomized controlled clinical trial to compare the clinical effects of IRE and RFA. The preliminary results suggest that both RFA and IRE are effective in the treatment of HCC, which can provide strong evidence for the use of IRE in HCC and provide more options for the treatment of patients with HCC.

Clinical trial registration: ClinicalTrials. gov, identifier NCT05451160.

Keywords: Ablation; HCC; Irreversible electroporation (IRE); Protocol; Radiofrequency ablation (RFA).

Fig. 1

Mechanisms of local ablative methods for treatment of hepatocellular carcinoma RFA: radiofrequency ablation; MWA: microwave ablation; IRE: irreversible electroporation. This figure was drawn from Figdraw website (https://www.figdraw.com/static/index.html)

Fig. 2

Flow chart of the study

Fig. 3

IRE positioning and IRE machine. (A. B) electrodes and equipment of IRE. (C. D. E) 2–4 electrodes positioning

Fig. 4

Probe position and patient posture during procedure

Fig. 5

Ultrasound-guided IRE procedure for HCC. (A) Pre-ablation contrast-enhanced MRI revealed a hepatocellular carcinoma. (B&C) Ultrasound and Contrast-enhanced ultrasound showed a tumor located in S6 (arrow). (D&E) Ultrasound-guided IRE with a two-electrode configuration, and the head and tail end of the active tip of the electrodes can have punctuated enhancements (arrow). (F) The contrast-enhanced MRI results of one-month after the ablation revealed the tumor shrank obviously and no enhancement after ablation (arrow)