A US multicenter registry on NanoKnife (irreversible electroporation, IRE) for pancreatic cancer was published in The Oncologist on 14 October 2026. Among 99 patients with stage III pancreatic cancer whose treatment included IRE after chemotherapy, median overall survival from diagnosis was 28 months, compared with 15 months for 38 patients who received standard care without IRE.
This article explains who the treatment was for, what the numbers show, side effects, and where IRE is available, using the figures exactly as reported.
Evidence level · NanoKnife is FDA-cleared in the US for soft tissue ablation, and in February 2026 its European indications were expanded to tumours of the pancreas, liver, kidney and prostate. The DIRECT study (NCT03899649) is an observational comparison of real-world patients; randomised trials are the next step to confirm the benefit. In Japan the device is not yet approved and a liver cancer study is under way. This is general information, not a recommendation.
What is new: the US DIRECT registry
DIRECT is a registry of patients with stage III pancreatic ductal adenocarcinoma run under an FDA investigational device exemption. The senior author is Robert C.G. Martin of the University of Louisville, with researchers from 12 US institutions including UC San Diego Moores Cancer Center, Miami Cancer Institute, Columbia University, Mayo Clinic, Washington University Siteman Cancer Center, NYU Langone and the University of Iowa. The study was sponsored by the device maker, AngioDynamics.
The team compared 99 patients treated with an IRE-based strategy with 38 patients who received standard care (chemotherapy, radiation and so on) without IRE. Propensity-score overlap weighting was the main analysis, and several other methods were used to check that the results pointed the same way.
What NanoKnife (IRE) is
Radiofrequency and microwave ablation destroy tumours with heat, which limits their use next to large blood vessels or bile ducts. IRE instead sends very short, strong electrical pulses between needle electrodes placed around the tumour, opening tiny pores in cancer cell membranes so that the cells die. Vessel walls and ducts are relatively preserved, which is why IRE has been studied in pancreatic cancer that wraps around major vessels.
The procedure is done under general anaesthesia with full muscle relaxation, and pulses are timed to the heartbeat. In this study 87 of 99 patients were treated during open surgery and 12 through the skin (percutaneously). See our RFA guide and IVR guide for background.
Who the patients were
- Stage: biopsy-confirmed AJCC stage III pancreatic ductal adenocarcinoma (locally advanced, not spread to distant organs)
- Fitness: ECOG 0–1 and able to tolerate general anaesthesia
- Response to chemotherapy: no progression after three months of standard chemotherapy
- Prior treatment: FOLFIRINOX in 51% (IRE) and 58% (standard care); prior radiation in 38% and 3%
In other words, IRE was not used on its own from the start; it was added as a local treatment after chemotherapy had stabilised the disease. Pancreatic Cancer UK likewise notes that IRE may suit some people with locally advanced cancer, and that heart conditions such as atrial fibrillation or a pacemaker may make it unsuitable.
Results: survival and side effects
| Measure | IRE-based strategy (99) | Standard care (38) |
|---|---|---|
| Median survival from diagnosis | 28 months (95% CI 23–33) | 15 months (12–21) |
| Median survival from enrolment* | 18 months | 10 months |
| Median progression-free survival from enrolment* | 9 months | 6 months |
| Risk of death (main analysis) | Hazard ratio 0.28 favouring IRE (95% CI 0.12–0.48) | |
| Mean survival within 24 months | 21.22 months | 16.24 months (difference 4.99) |
| Time from diagnosis to enrolment | 8 months | 4 months |
Martin RCG et al., The Oncologist 2026 (online 14 October), abstract. *Figures from the medRxiv preprint of the same study (May 2026).
When IRE was counted from the time it was given (a time-dependent analysis), the result pointed the same way with a hazard ratio of 0.59. Patients in the IRE group had a longer interval from diagnosis to enrolment, so more of them may have been patients who tolerated chemotherapy well. The authors therefore describe an IRE-based strategy as associated with longer survival and call for randomised trials to confirm the effect.
| Side effects (after enrolment)* | IRE-based strategy | Standard care |
|---|---|---|
| Any adverse event | 80% | 95% |
| Grade 3 or higher | 56% | 71% |
| Chemotherapy-related | 22% | 68% |
| IRE-related | 29% | Abdominal pain 8%, fatigue 5%, nausea, pancreatic fistula and vomiting 3% each |
*From the medRxiv preprint. A pancreatic fistula is a leak of pancreatic fluid, usually managed with a drain and medication.
Liver metastases: long-term results from three centres
Long-term IRE results are also being reported in other organs. On 23 September 2026 CVIR, the journal of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), published results from Amsterdam UMC, King's College Hospital London and Miami Cancer Institute for 162 patients (219 tumours) with colorectal liver metastases unsuitable for surgery or thermal ablation (median follow-up 33.7 months).
| Measure | 1 year | 3 years | Note |
|---|---|---|---|
| Local control (with repeat treatment) | 97.4% | 94.8% | Per tumour |
| Local progression-free, tumours ≤3 cm | 77.5% | 60.3% | Clearly better than tumours over 3 cm |
| Overall survival | 89.3% | 44.6% | 24.2% at 5 years, 14.0% at 10 years |
van der Lei S et al., Cardiovasc Intervent Radiol 2026 (online 23 September), abstract.
Adverse events occurred in 23.0% of procedures, 72.7% of them mild (grade 1–2), with no procedure-related deaths and a median hospital stay of one day. The authors conclude that IRE is a feasible and safe option at expert centres, and that recurrences could often be retreated to achieve durable local control.
Where it is available and regulatory status
| Region | Status | Source checked |
|---|---|---|
| United States | FDA 510(k) clearance for soft tissue ablation; prostate tissue ablation added in December 2024. No pancreas-specific indication; offered at individual centres | Urology Times, 2024 |
| Europe | Indications expanded in February 2026 to soft tissue ablation of liver, kidney, prostate and pancreas tumours | Interventional News, 2026 |
| United Kingdom | Described as suitable for some people with locally advanced pancreatic cancer; use alongside surgery is done within research | Pancreatic Cancer UK |
| Japan | Device not yet approved. Tokyo Medical University Hospital is running a clinical study in liver cancer unsuitable for surgery or RFA (target 45 patients) | jRCT registry (jRCTs032190083) |
Insurance coverage and costs vary by country, hospital and plan; international patients are often not covered by the host country's public insurance.
When looking at hospitals abroad, ask how many IRE procedures they perform each year, whether they use the open or percutaneous approach, and whether surgeons, oncologists and radiologists decide together.
What to check and questions to ask
- Study type: an observational study, not a randomised trial. Patients who tolerated chemotherapy well may be over-represented in the IRE group, so read the numbers as an association.
- Sequence: patients had chemotherapy first and no progression; stage IV disease was not included.
- Heart: because electrical pulses are used, tell the team about arrhythmias or a pacemaker.
- Funding: DIRECT was sponsored by the device maker, and conflicts of interest are disclosed.
Questions to ask your doctors:
- My cancer is stage III; given the vessel involvement, could IRE be considered?
- How many months of chemotherapy come first, and how does IRE compare with radiotherapy for me?
- Will it be open or percutaneous, and how long is the hospital stay?
- How many IRE procedures has this hospital done, and how are complications such as fistula or bleeding managed?
- When are follow-up CT scans and tumour markers done, and when does chemotherapy resume?
Related reading: PELICAN randomised trial of RFA for pancreatic cancer, five questions before an RFA consultation and how to check a study's phase.
Frequently asked questions
Which stage of pancreatic cancer is NanoKnife used for?
It has mainly been studied in locally advanced (stage III) pancreatic cancer that cannot be removed surgically. DIRECT included stage III patients without progression after three months of chemotherapy, and median survival from diagnosis in the IRE group was 28 months.
How is NanoKnife different from radiofrequency ablation?
RFA destroys tumours with heat, while NanoKnife uses short, strong electrical pulses to open pores in cancer cell membranes. Because it does not rely on heat, it can be tried for tumours next to large vessels or bile ducts.
How common are side effects?
In the DIRECT preprint, IRE-related adverse events occurred in 29% of patients, most often abdominal pain (8%), fatigue (5%) and nausea, pancreatic fistula or vomiting (3% each). Grade 3 or higher events overall were 56% with IRE and 71% with standard care.
Is it available in Japan?
The NanoKnife device is not yet approved in Japan, so it is not part of routine care; a liver cancer study is under way at Tokyo Medical University Hospital. For pancreatic cancer, hospitals in the US and Europe are the realistic options to explore.
This article summarises published papers and public information for general understanding and is not medical advice. Please discuss treatment decisions with doctors who have examined the patient.
Sources (checked 21 October 2026)
- Martin RCG 2nd, White RR, Bilimoria MM, Narayanan G, Kluger MD, et al. Association of Irreversible Electroporation Treatment with Overall Survival in Stage III Pancreatic Ductal Adenocarcinoma: DIRECT Registry Results. The Oncologist. 2026 Oct 14:oyag416. doi:10.1093/oncolo/oyag416 (PubMed 42872478)
- DIRECT Registry preprint. medRxiv, May 2026 (NCT03899649)
- van der Lei S, Dijkstra M, Ruiz EM, et al., Meijerink MR. Irreversible Electroporation for Colorectal Liver Metastases: Long-term Outcomes from a Transatlantic Multicenter Study. Cardiovasc Intervent Radiol. 2026 Sep 23. doi:10.1007/s00270-026-04617-x (PubMed 42778637)
- Interventional News. AngioDynamics expands European indications for NanoKnife system (24 February 2026)
- Urology Times. FDA grants clearance to NanoKnife System for prostate tissue ablation (9 December 2024)
- Pancreatic Cancer UK. Who can have irreversible electroporation (IRE)?
- Japan Registry of Clinical Trials. Efficacy of irreversible electroporation for hepatocellular carcinoma not eligible for resection or RFA (jRCTs032190083)