Objectives: Irreversible electroporation (IRE) is a novel non-thermal ablative technique applied in the treatment of unresectable locally advanced pancreatic cancer (LAPC). This paper reports on the initial experience with IRE of unresectable LAPC in our institution. Methods: From October 2013 to March 2018, patients with unresectable LAPC referred for IRE at the Department of Gastrointestinal Surgery, Aalborg University Hospital, were considered for inclusion in the study. Ninety-day morbidity, 30-day mortality, pain score, length of hospital stay (LOS) and overall survival (OS) were recorded. Results: We included 33 patients receiving 40 IRE ablations in total. The median visual analogue scale (VAS)-score was four (range 0–10) two hours after IRE, and one (range 0–8) eight hours after IRE. The median LOS was one day (range 1–13 days). Post-procedural complications occurred in 21 of 40 ablations (53%), of which eight (20%) were major (Clavien–Dindo grade III or more). A proportion of the observed complications might be attributed to disease progression and not IRE per se. Although not statistically significant, we observed increased severity of complications in tumors above 3.5 cm. The 30-day mortality was 5% (2/40). The median OS was 10.7 months (range 0.6–53.8 months) from the initial IRE procedure, and 18.5 months (range 4.9–65.8 months) from time of diagnosis. Conclusions: In our institution, IRE seems as a feasible consolidative treatment of unresectable LAPC with an acceptable safety profile. The oncological outcome of IRE in patients with unresectable LAPC is to be further evaluated in a planned phase 2 clinical trial (CHEMOFIRE-2).

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

Preclinical studies suggest that irreversible electroporation (IRE) increases the effect of immune checkpoint inhibition in pancreatic cancer (PC). Patients with PC received PD-1 inhibitor pembrolizumab and, on day 10, percutaneous IRE of a liver metastasis. Blood samples were analyzed for immune cell subsets and inflammation related proteins. mRNA expression profiling was done in sequential biopsies. Treatment was safe, but the trial was terminated early. The response rate in eight patients was 0% and tumor growth was exponential. A drop in circulating plasmacytoid dendritic cells and a rise in several cytokines and proteins, especially PD-1, after immunotherapy was observed. In liver metastases, immune stimulatory genes were upregulated and immune suppressive genes were downregulated after pembrolizumab, while markers of effector T cells were unchanged. Treatment was safe but showed no efficacy in PC. Immunotherapy induced an immune permissive tumor microenvironment but with no increase in effector cells.

Irreversible electroporation (IRE) is a novel anticancer ablative treatment, which has been proposed to enhance the efficacy of chemotherapy in the periphery of the ablated area by capturing chemotherapy intracellularly. The aim of the current trial was to characterize the ablated lesion to get spatial information about the distribution of captured chemotherapy and in extension to assess the a priori probability of efficacy for the combined intervention. IRE ablations were performed in five pigs with or without concurrent intravenous bleomycin and gadolinium contrast injection. Magnetic resonance (MR) scans were performed to examine the distribution of contrast in the ablated areas and images were segmented to quantify the volumes of the ablations. Pig plasma and tissues were analyzed for bleomycin using quantitative liquid chromatography mass spectrometry. MR images showed a hypointense inner surrounded by a hyperintense outer penumbra effectively doubling the volume of the ablated lesion, when gadolinium contrast and bleomycin were given just prior to IRE. In contrast, the ablations without prior contrast and bleomycin only produced a small or no hyperintense area. Bleomycin was not detectable in any of the examined tissue samples. A contrast enhancing penumbra can be visualized using clinically available MRI aligning with theoretical models. Regions of transient permeability may expand the apparent margins after IRE. However, this study does not provide direct evidence of intracellular bleomycin entrapment and thus results should be interpreted with caution.