Novel irreversible electroporation ablation (Nano-knife) versus radiofrequency ablation for the treatment of solid liver tumors: a comparative, randomized, multicenter clinical study

Abstract

Irreversible electroporation (IRE) is a soft tissue ablation technique that uses short electrical fields which induce the death of target cells. To evaluate the safety and efficacy of an IRE-based device compared to regular radiofrequency ablation (RFA) of solid liver tumors, in this multicenter, randomized, parallel-arm, non-inferiority study, 152 patients with malignant liver tumors were randomized into IRE (n = 78) and RFA (n = 74) groups. The primary endpoint was the success rate of tumor ablation; the secondary endpoints included the tumor ablation time, complications, tumor recurrence rates and treatment-related adverse events (TRAE). The success rate of tumor ablation using IRE was 94.9% and was non-inferior to the RFA group (96.0%) (P = 0.761). For the secondary endpoints, the average ablation time was 34.29 ± 30.38 min for the IRE group, which was significantly longer than for the RFA group (19.91 ± 16.08 min) (P < 0.001). The incidences of postoperative complications after 1 week (P = 1.000), 1 month (P = 0.610) and 3 months (P = 0.490) were not significantly different between the 2 groups. The recurrence rates of liver tumor at 1, 3 and 6 months after ablation were 0 (0.0%), 10 (13.9%) and 10 (13.3%) in the IRE group and 2.9%, 7.3% and 19.7% in the RFA control group (all P > 0.05), respectively. For safety assessments, 51 patients experienced 191 AEs (65.4%) in the IRE group, which was not different from the RFA group (73.0%, 54/184) (P = 0.646). In 7 IRE patients, 8 TRAEs (7.9%) occurred, the most common being edema of the limbs (mild grade) and fever (severe grade), while no TRAEs occurred in the RFA group. This study proved that the excellent safety and efficacy of IRE was non-inferior to the regular radiofrequency device in ablation performance for the treatment of solid liver tumors. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1800017516.

Keywords: ablation; hepatocellular carcinoma; irreversible electroporation-based ablation (IRE); liver cancer; radiofrequency.

Figure 1

IRE procedure (A, B) During the operation, four 19G ablation probes were used to puncture the edges of the lesion. The active tip length (ablation area) was 15 mm, the voltage-to-distance ratio was 1,500-1,800 V/cm, and the pulse length was 90 μs. (C) The probes were pulled back twice to make segmental ablation. (D) Immediate postoperative enhanced scan showed decreased enhancement in the ablation area and a scattered gas density shadow, and no damage was found in the surrounding portal vein structure.

Figure 2

Schematic diagram of pulse waveform used with the device.A single pulse width was 90 μs or 100 μs and the number of ablation pulses in a single group was generally 70-100. The pulse was released during the absolute refractory period of the cardiac cycle with synchronous detection by ECG in the whole ablative period. In the ablation process, the pulses were discharged from positive and negative direction alternatively, and the absolute value of pulse discharge voltage in one group was the same.

Figure 3

Flowchart of the study.