Irreversible Electroporation in Pancreatic Cancer

Pancreatic cancer is the deadliest of the gastrointestinal tract with 5-year survival rates of less than 5%. Given common asymptomatic early disease course, most patients (50%) present with an already metastatic disease, while only 20% can undergo potentially curative resection. The remaining 30% present with locally advanced disease, defined as extended vascular encasement, where the risk of surgical therapy often outweighs its benefits. Traditional thermal local ablative modalities (RFA, MWA, or cryotherapy) have the disadvantage that they are not applicable in proximity to vital vascular structures, which are abundant in the peripancreatic region. Irreversible electroporation (IRE) is an emerging non-thermal alternative that induces apoptosis of tumor cells by the delivery of short repetitive impulses of high-voltage electric current. Given its mostly non-thermal modality, IRE is not hampered by a heat-sink effect and is applicable with little risk around vascular structures, bile and pancreatic ducts. Recent research suggests that local tumor destruction through IRE improves overall survival, progression-free survival and quality of life in patients with locally advanced pancreatic cancer

Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy

Systematic review of irreversible electroporation role in management of locally advanced pancreatic cancer

Background: Ablative techniques provide in patients with locally advanced pancreatic cancer (LAPC) symptomatic relief, survival benefit and potential downsizing. Irreversible Electroporation (IRE) represents potentially an ideal solution as no thermal tissue damage occurs. The purpose of this review is to present an overview on safety, feasibility, oncological results, survival and quality of life improvement obtained by IRE. Methods: A systematic search was performed in PubMed, regarding the use of IRE on PC in humans for studies published in English up to March 2019. Results: 15 original studies embodying 691 patients with unresectable LAPC who underwent IRE were included. As emerged, IRE works better on tumour sizes between 3–4 cm. Oncological results are promising: median OS from diagnosis or treatment up to 27 months. Two groups investigated borderline resectable tumours treated with IRE before resection with margin attenuation, whereas IRE has proved to be effective in pain control. Conclusions: Electroporation is bringing new hopes in LAPC management. The first aim of IRE is to offer a palliative treatment. Further efforts are needed for patient selection, as well as the use of IRE for ‘margin accentuation’ during surgical resection. Even if promising, IRE needs to be validated in large, randomized, prospective series

Computer Assistance in the Minimally Invasive Ablation Treatment of Pancreatic Cancer

The insertion of ablation needles towards pancreatic tumors demands excellent anatomical knowledge and interdisciplinary skills from the medical professional. While the placement of a single needle next to the structures at risk surrounding the pancreas is considered a challenging task, irreversible electroporation requires multiple needles to be placed in parallel at a specific location. Minimally invasive procedures complicate the already ambitious procedure, yet the ablation method bears potential to increase the overall survival for patients with locally advanced pancreatic cancer. Current studies require more clinical evidence regarding the efficacy of irreversible electroporation in pancreatic cancer by means of randomized controlled, multicenter trials. However, the ablation treatment is currently applied in expert centers only, which is due to the complex task of the needle placement. Computer-assisted surgery has shown its potential in different fields of applications to improve the targeting of diseased tissue and the confidence of the medical professional. The application of computer-assisted needle navigation for pancreatic cancer ablation holds the prospect to make the procedure more reproducible and safer

Ablation of the locally advanced pancreatic cancer: An introduction and brief summary of techniques

Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option. Ablative techniques use various forms of energy to cause local tissue destruction through necrosis or apoptosis. They are relevant in pancreatic ductal adenocarcinoma as they are a treatment option in non-resectable tumors where their use ranges from symptom control to reducing tumor size for resection. In this narrative review we have grouped and outlined the various ablative methods, classifying them into thermal (Radiofrequency ablation, Microwave ablation, High Intensity Focused Ultrasound ablation, Cryoablation), and non-thermal ablative methods (Irreversible Electroporation (NanoKnife®), Photodynamic Therapy). This is followed by a description and review of the available evidence on survival and complications for each of these ablative methods. According to the literature, thermal ablative methods appear to be more accessible but are implicated with more complications than non thermal ablative methods which show the most promise

Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols

Background: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. Methods: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only

Pancreatic cancer

Cáncer de páncreasCàncer de pàncreesPancreatic cancerThe need for a common education and training track in surgical oncology across Europe has been emphasized. ESSO provides several hands-on courses for skills training and face-to-face discussions. The core curriculum provides a framework for the overall theoretical requirements in surgical oncology. The UEMS/EBSQ fellowship exam is designed to test core competencies in the candidate's core knowledge in their prespecified area of expertise. A core set of points for each cancer type is lacking. Hence, a condensed outline of themed expected to be covered in the curriculum and relevant to an optimal practice in surgical oncology is provided. This article outlines pancreatic cancer

Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial)

Background: We conducted a multicentre phase II trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer (LAPC), (LAPC-1 trial). Methods: Patients with biopsy-proven LAPC treated in four hospitals in the Netherlands between December 2014 and June 2017. Patients received 8 cycles of FOLFIRINOX followed by SBRT (5 fractions/8 Gy) if no tumour progression after the FOLFIRINOX treatment was observed. Primary outcome was 1-year overall survival (OS). Secondary outcomes were median OS, 1-year progression-free survival (PFS), treatment-related toxicity, and resection rate. The study is registered with ClinicalTrials.gov, NCT02292745, and is completed. Findings: Fifty patients were included. Nineteen (38%) patients did not receive all 8 cycles of FOLFIRINOX, due to toxicity (n = 12), disease progression (n = 6), or patients’ preference (n = 1). Thirty-nine (78%) patients received the SBRT treatment. The 1-year OS and PFS were 64% (95% CI: 50%-76%) and 3

Predicting disease recurrence in pancreatic ductal adenocarcinoma

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is one of the most lethal tumour types worldwide. The majority of patients present late with locally advanced or metastatic disease. Therefore, despite advances in operative techniques, perioperative management and oncological treatments, the overall 5-year survival remains <5%. The reason for poor survival is due to disease recurrence even after curative surgical resection for small tumours. Determining factors that lead to disease recurrence may help in identifying those with a poor prognosis so that treatment options can be tailored to each patient. We investigated whether operative technique, clinicopathological factors or specific genetic mutations could influence disease recurrence. Further, we sought to identify a biomarker in the peripheral circulation that could be used as a prognostic marker. We confirmed that a positive medial resection margin and a high frequency of KRAS mutation in the tumour tissue result in early disease recurrence. Further, that the altered expression of five microRNAs may be useful as a blood-based prognostic predictor.Open Acces