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Simple Summary: Locoregional therapies play an ever-increasing role in contemporary oncology. This review provides an up-to-date, informed analysis of locoregional therapies harnessing electric pulses. Irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are integral to the therapeutic strategy in several solid tumours, ranging from skin cancers to visceral and bone metastases. Still, despite consolidated credibility and a favourable trade-off between efficacy and side effects, these therapies face fragmentation, as shown by differences in the stage of development and regulatory approval worldwide. Here, leading experts convened at the 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provide a coherent, updated snapshot of this field. Hopefully, these techniques' common scientific and technological ground will allow researchers to overcome knowledge barriers and develop synergistic strategies to improve patient outcomes. The 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies. [ABSTRACT FROM AUTHOR]

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pretreatment information and evaluation, treatment choices, as well as follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Electrochemotherapy (ECT) combines a cytotoxic agent with locally applied electric pulses to enhance its antitumor effect. Over the last 15 years, ECT has been safely applied to patients with skin metastases in combination with other oncologic treatments and, more recently, with systemic immunotherapy. In this study, we aimed to investigate the effectiveness of ECT in combination with pembrolizumab. We compared patient outcomes after the following treatments: (a) pembrolizumab, (b) pembrolizumab and ECT, and (c) ECT alone. The combined application of pembrolizumab and ECT was safe and more efficacious in preventing further growth of cutaneous metastases than pembrolizumab alone. The patients treated with pembrolizumab and ECT experienced lower disease progression rates and longer survival than those who received pembrolizumab. ECT may boost the effect of pembrolizumab by acting as an in situ vaccination against cancer cells. Further studies are required to confirm these findings. Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation. [ABSTRACT FROM AUTHOR]