= 23), ccc (n = 2), other (n = 22); 3.8 cm percutaneous (ns) open (ns) 18 ns ns scheffer et al., 2014 10 / 10 crlm (n = 10), 2.4 cm open (n = 10) 0 88.9 ns thomson et al., 2011 25 / 63 hcc (n = 17), crlm (n = 15), other (n = 31); 2.5 cm percutaneous (n = 25) 3 51.6 56.5 hepatic ire appears to be safe, even when performed near vessels and bile ducts with an overall complication rate of 16%, with most complications being needle related (pneumothorax and hemorrhage).the coldfire-2 trial with 50 patients showed 76% local tumor progression-free survival after 1 year. whilst there are no studies comparing ire to other ablative therapies yet, thermal ablations have shown a higher efficacy in that matter with around 96% progression free survival. therefor bart et al. concluded that ire should currently only be performed for only truly unresectable and non-ablatable tumors. pancreas table 2: irreversible electroporation clinical data in the pancreas author, year no. of patients stage of disease and median largest tumor diameter approach median follow-up (mo) median overall survival (mo) local recurrence (%) tumor downstaging caused by ire belfiore et al., 2017 29 lapc, ns percutaneous 29 14.0 3 3 patients flak et al., 2019 33 lapc, 3.0 cm (88% after chemotherapy or radiation therapy) percutaneous (n = 32), open (n = 1) 9 18.5 (diagnosis), 10.7 (ire) ns 3 patients kluger et al., 2016 50 lapc t4, 3.0 cm open 8,7 12.0 (ire) 11 ns lambert et al., 2016 21 lapc, 3.9 cm open (n = 19), percutaneous (n = 2) ns 10.2 ns ns leen et al., 2018 75 lapc, 3.5 cm (after chemotherapy) percutaneous 11.7 27.0 (ire) 38 3 patients månsson et al., 2016 24 lapc, ns (after chemotherapy) percutaneous ns 17.9 (diagnosis), 7.0 (ire) 58 2 patients månsson et al., 2019 24 lapc, 3.0 cm (before chemotherapy) percutaneous ns 13.3 (diagnosis) 33 0 martin et al., 2015 150 lapc, 2.8 cm (after chemo- or radiation therapy) open 29 23.2 (diagnosis), 18 (ire) 2 ns narayanan et al., 2016 50 lapc, 3.2 cm 6 1.3 (after chemo- or radiation therapy) percutaneous ns 27 (diagnosis), 14.2 (ire) ns 3 patients paiella et al., 2015 10 lapc, 3.0 cm open 7.6 15.3 (diagnosis), 6.4 (ire) ns ns ruarus et al., 2019 50 lapc (n = 40) and local recurrence (n = 10), 4.0 cm (68% after chemotherapy) percutaneous ns 17.0 (diagnosis), 9.6 (ire) 46 0 patients scheffer et al., 2017 25 lapc, 4.0 cm (52% after chemotherapy) percutaneous 12 (7–16) 17.0 (diagnosis), 11.0 (ire) ns ns sugimoto et al., 2018 8 lapc, 2.9 cm open or percutaneous, ns 17.5 17.5 (diagnosis) 38 0 patients vogel et al., 2017 15 lapc, ns open 24 16 (diagnosis) ns ns yan et al., 2016 25 lapc, 4.2 cm open 3 ns 2 ns zhang et al., 2017 21 lapc, 3.0 cm percutaneous 1 ns ns ns animal studies have shown the safety and efficacy of ire on pancreatic tissue. the overall survival rates in studies on the use of ire for pancreatic cancer provide an encouraging nonvariable endpoint and show an additive beneficial effect of ire compared with standard-of care chemotherapeutic treatment with folfirinox (a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) (median os, 12–14months). however, ire appears to be more effective in conjunction with systemic therapy and is not suggested as first-line treatment. despite that ire makes adjuvant tumor mass reduction therapy for lapc possible, ire remains, in its current state, a high risk procedure requiring additional safety data before it can be used widely. prostate table 3: irreversible electroporation clinical data in the prostate author, year no. of patients gleason score pretreatment or concurrent treatment adverse events, 1/2/3/4/5 functional outcome (% of patients) oncologic efficacy (no. of patients) comments onik and rubinsky (2010) 16 3+3: n = 7 3+4: n = 6 4+4: n = 3 ns nr at 6 months: urinary incontinence 0% erectile dysfunction 0% local recurrence, n = 0; out-of-field occurrence, n = 1 adequate flow in nvb postoperative van den bos et al. (2016) 16 3+3: n = 8 4+3: n = 3 4+4: n = 2 radical prostatectomy 4 weeks after ire 15/8/1/0/0 ns 15 patients showed complete fibrosis or necrosis of ablation zone electrode configuration completely enveloped ablation, leaving no viable cells in 15 patients van den bos et al. (2018) 63 3+3: n = 9 3+4: n = 38 4+3: n = 16 concurrent turp (n = 10) grade 1: 24% grade 2: 11% grade 3–5: 0% at 12 months: urinary incontinence 0%; erectile dysfunction 23% local recurrence, n = 7; out-of-field recurrence, n = 4 safe and effective guenther et al. (2019) 429/471 3+3: n = 82 3+4/4+3: n = 225 4+4: n = 68 5+3/3+5: n = 3 >4+4 = 42 pretreated with: radical prostatectomy (n = 21), radiation therapy (n = 28), turp (n = 17), hifu (n = 8) adt (n = 29) 93/17/7/0/0 at >=12 months: urinary incontinence 0%; erectile dysfunction 3% after up to 6y: local recurrence, n = 20; out-of-field recurrence, n = 27 comparable 5-year recurrence free survival to radical prostatectomy with improved urogenital outcomes valerio et al. (2014) 34 3+3: n = 9 3+4: n = 19 4+3: n = 5 4+4: n = 1 ns 12/10/0/0/0 at 6 months: urinary incontinence 0%; erectile dysfunction 5% local residual disease, n = 6; only one histologic verification. out-of-field recurrence, ns average ablation volume of 12ml ting et al. (2016) 25 3+3: n = 2 3+4: n = 15 4+3: n = 8 4+4: n = 0 none grade 1: 35% grade 2: 29% grade 3–5: 0% at 6 months: urinary incontinence 0%; erectile dysfunction, unknown local recurrence, n = 0; out-of-fieldrecurrence, n = 5 (with histologic verification) good oncological control achieved with low toxicity blazevski et al. (2020) 50 3+3: n = 5 3+4: n = 37 4+3: n = 6 4+4: n = 2 ns grade 1: 10 grade 2: 9 grade 3–5: 0% incontinence 2% (study only focused apical lesions); erectile dysfunction 6% local recurrence, n=1 out-of-field recurrence, ns study only focused on apical lesions (difficult to treat with other methods without causing impotence and incontinence). focal ablation using ire for pca in the distal apex appears safe and feasible. the concept of treating prostate cancer with ire was first proposed by gary onik and boris rubinsky in 2007. prostate carcinomas are frequently located near sensitive structures which might be permanently damaged by thermal treatments or radiation therapy. the applicability of surgical methods is often limited by accessibility and precision. surgery is also associated with a long healing time and high rate of side effects. using ire, the urethra, bladder, rectum and neurovascular bundle and lower urinary sphincter can potentially be included in the treatment field without creating (permanent) damage. ire has been in use against prostate cancer since 2011, partly in form of clinical trials, compassionate care or individualized treatment approach. as for all other ablation technologies and also most conventional methods, no studies employed a randomized multi-center approach or targeted cancer-specific mortality as endpoint. cancer-specific mortality or overall survival are notoriously hard to assess for prostate cancer, as the trials require more than a decade and usually several treatment types are performed during the years making treatment-specific survival advantages difficult to quantify. therefore, the results of ablation-based treatments and focal treatments in general usually use local recurrences and functional outcome (quality of life) as endpoint. in that regard, the clinical results collected so far and listed in table 3 shown encouraging results and uniformly state ire as a safe and effective treatment (at least for focal ablation) but all warrant further studies. the largest cohort presented by guenther et al. with up to 6-year follow-up is limited as a heterogeneous retrospective analysis and no prospective clinical trial. therefore, despite that several hospitals in europe have been employing the method for many years with one private clinic even listing more than one thousand treatments as of june 2020, ire for prostate cancer is currently not recommended in treatment guidelines. kidney while nephron-sparing surgery is the gold standard treatment for small, malignant renal masses, ablative therapies are considered a viable option in patients who are poor surgical candidates. radiofrequency ablation (rfa) and cryoablation have been used since the 1990s; however, in lesions larger than 3 cm, their efficacy is limited. the newer ablation modalities, such as ire, microwave ablation (mwa), and high-intensity focused ultrasound, may help overcome the challenges in tumor size. the first human studies have proven the safety of ire for the ablation of renal masses; however, the effectiveness of ire through histopathological examination of an ablated renal tumor in humans is yet to be known. wagstaff et al. have set out to investigate the safety and effectiveness of ire ablation of renal masses and to evaluate the efficacy of ablation using mir and contrast-enhanced ultrasound imaging. in accordance with the prospective protocol designed by the authors, the treated patients will subsequently undergo radical nephrectomy to assess ire ablation success. later phase 2 prospective trials showed good results in terms of safety and feasibility for small renal masses but the cohort was limited in numbers (7 and 10 patients respectively), hence efficacy is not yet sufficiently determined. ire appears safe for small renal masses up to 4 cm. however, the consensus is that current evidence is still inadequate in quality and quantity. lung in a prospective, single-arm, multi-center, phase ii clinical trial, the safety and efficacy of ire on lung cancers were evaluated. the trial included patients with primary and secondary lung malignancies and preserved lung function. the expected effectiveness was not met at interim analysis and the trial was stopped prematurely. complications included pneumothoraces (11 of 23 patients), alveolar hemorrhage not resulting in significant hemoptysis, and needle tract seeding was found in 3 cases (13%). disease progression was seen in 14 of 23 patients (61%). stable disease was found in 1 (4%), partial remission in 1 (4%) and complete remission in 7 (30%) patients. the authors concluded that ire is not effective for the treatment of lung malignancies. similarly poor treatment outcomes have been observed in other studies. a major obstacle of ire in the lung is the difficulty in positioning the electrodes; placing the probes in parallel alignment is made challenging by the interposition of ribs. additionally, the planned and actual ablation zones in the lung are dramatically different due to the differences in conductivity between tumor, lung parenchyma, and air. coronary arteries maor et el have demonstrated the safety and efficiency of ire as an ablation modality for smooth muscle cells in the walls of large vessels in rat model. therefore, ire has been suggested as preventive treatment for coronary artery re-stenosis after percutaneous coronary intervention. pulmonary veins numerous studies in animals have demonstrated the safety and efficiency of ire as a non-thermal ablation modality for pulmonary veins in context of atrial fibrillation treatment. ire's advantages in comparison with rf-ablation and cryoablation are: well defined ablation area and the lack of peripheral thermal damage. therefore, ire has been suggested as a part of novel treatment for atrial fibrillation. other organs ire has also been investigated in ex-vivo human eye models for treatment of uveal melanoma and in thyroid cancer. successful ablations in animal tumor models have been conducted for lung, brain, heart, skin, bone, head and neck cancer, and blood vessels.