Electric Fields, Not Heat: Non-Thermal Ablation Shows Promise for Hard-to-Treat Liver Cancer

Hepatocellular carcinoma, the most common form of primary liver cancer, remains one of the world’s deadliest malignancies and the second leading cause of cancer-related death. For patients diagnosed early, the curative menu is short: liver transplantation, surgical resection, or thermal ablation, in which radiofrequency or microwave energy is used to cook the tumour to death. But a substantial minority of patients fall through the gaps. Their tumours may sit dangerously close to bile ducts, major blood vessels, the gallbladder or bowel, making heat-based treatment either unsafe or ineffective. For these individuals, a team at a tertiary liver centre in London has now reported encouraging long-term results with a strikingly different approach: destroying tumours with bursts of high-voltage electricity rather than heat.

The technique, known as irreversible electroporation, or IRE, works on an entirely different physical principle from conventional ablation. Between two and six thin needle-electrodes are placed around the tumour, and short, intense electric pulses are fired between them. The resulting electric field is strong enough to destabilise the cell membrane itself, punching nanoscale pores into the lipid bilayer. These pores allow the cell’s contents to leak out and trigger apoptosis, a form of programmed cell death, rather than the coagulative necrosis produced by burning or freezing tissue. Because the mechanism is predominantly non-thermal, the collagen scaffolding of ducts and vessels within the treated zone is largely preserved, a property that makes the technique attractive precisely where thermal energy would be most hazardous.

Crucially, IRE also sidesteps the so-called heat sink effect, the Achilles heel of radiofrequency and microwave ablation. When a tumour abuts a large blood vessel, flowing blood continuously carries heat away from the ablation zone, leaving a rim of viable tumour cells that can seed recurrence. Since IRE does not rely on raising tissue temperature, blood flow confers no such protection, and the ablation zone remains predictable even immediately adjacent to major vessels. The technique is not entirely free of thermal effects, the authors caution; temperature rises have been documented near the needle tips during long pulses at very high voltages, a detail that must inform needle placement. Still, the absence of a clinically meaningful heat sink is the central reason IRE has carved out a niche for tumours hugging the portal triad, hepatic veins, inferior vena cava, gallbladder and bowel.

In the new study, published in CVIR Oncology, researchers retrospectively analysed 56 IRE procedures performed in 54 patients at their centre between February 2014 and February 2022. All patients had solitary tumours smaller than three centimetres that a multidisciplinary team had deemed unsuitable for surgery or thermal ablation because the lesions lay within five millimetres of critical structures. The median tumour size was 22 millimetres, and the median age of patients was 61 years. Most had underlying liver disease, with hepatitis C infection and alcohol-related liver disease the most common risk factors, and all patients had well-preserved liver function, classified as Child-Pugh A. Twenty-three patients had already undergone transarterial chemoembolization for larger tumours and still harboured residual disease, while five had recurrent tumours at sites of previous thermal ablation or surgery; the remaining 26 were treatment-naive.

The procedures themselves are technically demanding. Performed under general anaesthesia with deep neuromuscular blockade to eliminate involuntary muscle contraction, they were carried out by interventional radiologists with more than a decade of ablation experience, using CT guidance to position the needles. Accurate probe parallelism, three-dimensional orientation and inter-needle spacing, maintained between 15 and 25 millimetres, are critical to success. Using the NanoKnife system, the team delivered a standard regimen of 90 pulses per electrode pair at voltages between 1000 and 1500 volts, producing currents of 20 to 40 amperes. For larger or irregularly shaped lesions, the electrodes were withdrawn by about a centimetre and a further 90 pulses delivered to extend the ablation margin, a manoeuvre performed in more than three-quarters of cases. Technical success, defined as completion of the full pulse protocol, was achieved in all 56 procedures.

The oncological results were encouraging. On the first follow-up scan four to six weeks after treatment, assessed with the modified Response Evaluation Criteria in Solid Tumours, radiologic complete response was achieved after 83.9 percent of procedures. Neither age, sex, tumour size, adjacent anatomy nor previous treatment significantly influenced the likelihood of complete response. Over a median imaging follow-up of 31.7 months, local recurrence after an initial complete response occurred in 15 of 47 procedures, or 31.9 percent. Mean local tumour progression-free survival was 41.6 months, with 91.5 percent of patients free of local progression at six months, 78.4 percent at one year and 73.7 percent at two years. Notably, outcomes were statistically indistinguishable between treatment-naive patients and those who had undergone prior locoregional therapy, suggesting IRE performs reliably regardless of tumour history.

Safety data were equally important. There were no procedure-related deaths within 30 days, and the overall complication rate was 10.7 percent, with only two major complications, both graded IIIa on the Clavien-Dindo scale: a haemothorax attributed to suspected intercostal artery injury, managed with angiography and chest drainage, and a pneumothorax treated with needle aspiration. Minor complications included transient post-ablation syndrome in two patients and asymptomatic portal vein thrombosis in two others, detected on follow-up imaging. One of these thromboses resolved fully with anticoagulation, while the other led to right lobe atrophy and secondary bile duct damage. The authors point out that although IRE is designed to spare vessels, the tissue swelling that follows treatment can compress adjacent vascular structures and promote thrombosis, and that needles should never be passed directly through vessels. Tumour seeding, a feared complication of needle-based therapies, was not observed, possibly because IRE needles bracket the tumour rather than traversing it.

The findings place IRE within a rapidly evolving therapeutic landscape. The authors note that fewer than 20 percent of patients with early-stage disease are suitable for resection, and donor shortages constrain transplantation, so percutaneous options carry disproportionate weight. Selective internal radiotherapy, in which yttrium-90 microspheres are delivered into the tumour’s arterial supply, has produced excellent results in recent trials, with the LEGACY study reporting three-year overall survival of 86.6 percent and local control above 90 percent for solitary unresectable tumours, and newer single-session workflows eliminating the need for a separate mapping angiogram. Stereotactic body radiotherapy likewise delivers local control rates of 80 to 95 percent at two to three years without requiring anaesthesia, though both alternatives involve radiation exposure, logistical complexity and cost, and both are limited by proximity to radiosensitive organs and by compromised liver function.

IRE, by contrast, demands general anaesthesia, has a genuine learning curve, takes longer than thermal ablation and uses more expensive electrodes. Bracketing a tumour with four to six parallel needles is particularly challenging for central lesions or those near the dome of the liver approached between the ribs, and the study found that tumours larger than two centimetres required significantly more needles than smaller ones. Overlapping treatments with too few needles, the authors warn, yield higher rates of incomplete ablation. These practical constraints mean the technique is best reserved for carefully selected patients: those with small tumours adjacent to bile ducts, the hepatic hilum, gallbladder, bowel or central vasculature, who are unfit for surgery but can tolerate general anaesthesia, and in whom immediate local control is the priority.

For a disease in which anatomical bad luck often forecloses curative treatment, the message from this single-centre experience is quietly significant. With complete response rates comparable to published IRE series and to thermal ablation of perivascular tumours, and safety figures in the same range as heat-based techniques despite the hostile anatomy of the treated lesions, irreversible electroporation appears to be a viable definitive option for a patient group that has long had few. The retrospective design and modest sample size mean randomised comparisons with radioembolization and stereotactic radiotherapy remain desirable, but the study suggests that for small, anatomically treacherous hepatocellular carcinomas, the answer may lie not in turning up the heat, but in switching off the heat altogether.

Subject of Research: Irreversible electroporation as a non-thermal treatment for early-stage hepatocellular carcinoma unsuitable for thermal ablation

Article Title: Irreversible electroporation as a definitive treatment for early-stage HCC unsuitable for thermal ablation: insights from a tertiary liver centre

Article References: Peddu, P., Seneviratne, N., Hashem, E., & Fang, C. (2025). Irreversible electroporation as a definitive treatment for early-stage HCC unsuitable for thermal ablation: insights from a tertiary liver centre. CVIR Oncology, 1(1), Article 17. https://doi.org/10.1007/s44343-025-00018-y

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00018-y

Keywords: hepatocellular carcinoma, irreversible electroporation, thermal ablation, liver cancer, interventional radiology, heat sink effect, locoregional therapy, radiofrequency ablation, microwave ablation, transarterial chemoembolization, radioembolization, stereotactic body radiotherapy