Irreversible Electroporation in Locally Advanced Pancreatic Cancer: Potential Improved Overall Survival

Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA, .
Annals of Surgical Oncology (Impact Factor: 3.93). 11/2012; 20(S3). DOI: 10.1245/s10434-012-2736-1
Source: PubMed


Locally advanced unresectable pancreatic adenocarcinoma (LAC) is characterized by poor survival despite chemotherapy and conventional radiation therapy. We have recently reported on the safety of using irreversible electroporation (IRE) for the management of LAC. The purpose of this study was to evaluate the overall survival in patients with LAC treated with IRE.

A prospective, multi-institutional evaluation of 54 patients who underwent IRE for unresectable pancreatic cancer from December 2009 to October 2010 was evaluated for overall survival and propensity matched to 85 matched stage III patients treated with standard therapy defined as chemotherapy and radiation therapy alone.

A total of 54 LAC patients have undergone IRE successfully, with 21 women, 23 men (median age, 61 (range, 45-80) years). Thirty-five patients had pancreatic head primary and 19 had body tumors; 19 patients underwent margin accentuation with IRE and 35 underwent in situ IRE. Forty-nine (90 %) patients had pre-IRE chemotherapy alone or chemoradiation therapy for a median duration 5 months. Forty (73%) patients underwent post-IRE chemotherapy or chemoradiation. The 90 day mortality in the IRE patients was 1 (2 %). In a comparison of IRE patients to standard therapy, we have seen an improvement in local progression-free survival (14 vs. 6 months, p = 0.01), distant progression-free survival (15 vs. 9 months, p = 0.02), and overall survival (20 vs. 13 months, p = 0.03).

IRE ablation of locally advanced pancreatic tumors remains safe and in the appropriate patient who has undergone standard induction therapy for a minimum of 4 months can achieve greater local palliation and potential improved overall survival compared with standard chemoradiation-chemotherapy treatments. Validation of these early results will need to be validated in the current multi-institutional Phase 2 IDE study.

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    • "We and other authors have recently demonstrated the safety of the use of IRE around vascular and ductile structures on chronic large animal models [4–6]. Subsequent to those studies we have recently published organ specific safety and efficacy data with the use of IRE in liver and pancreas [7–9]. As with any novel technology in clinical practice, initial experience can be used to tailor subsequent indications, applications and strategies to limit the morbidity of the procedure. "
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    ABSTRACT: Background Irreversible electroporation (IRE) has recently been added as an additional therapeutic ablative option in patients with locally advanced cancers (LAC) involving vital structures. IRE delivers localized electric current by peri-tumoral discrete probes to attain irreversible changes in cell membrane leading to cell death. The aim of this study was to evaluate the long-term effects of IRE in the treatment of locally advanced tumors. Methods A prospective IRB approved evaluation of 107 consecutive patients from 7 institutions with tumors that had vascular invasion treated with IRE from 5/2010 to 1/2012. LAC was defined as primary tumor with <5 mm from major vascular structure based on pre-operative dynamic imaging or intra-operative criteria. Results IRE as utilized in LAC in the liver (N = 42, 40%) and pancreas (N = 37, 35%), with a median number of lesions being 2 with a mean target size of 3 cm. IRE attributable morbidity rate was 13.3% (total 29.3%) with high-grade complications seen in 4.19% (total 12.6%). No significant vascular complications were seen, and of the high-grade complications, bleeding (2), biliary complications (3) and DVT/PE (3) were the most common. Complications were more likely with pancreatic lesions (p = 0.0001) and open surgery (p = 0.001). Calculated local recurrence free survival (LRFS) was 12.7 months with a median follow up of 26 months censured at last follow up. The tumor target size was inversely associated with recurrence free survival (b = 0.81, 95% CI: 1.6 to 4.7, p value = 0.02) but this did not have a significant overall survival impact. Conclusions IRE represents a novel therapeutic option in patients with LAC involving vital structures that are not amenable to surgical resection. Acceptable to high local disease control and the long LRFS can be achieved with this therapy in combination with other multi-disciplinary therapies.
    Full-text · Article · Jul 2014 · BMC Cancer
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    ABSTRACT: Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally evaluated in tissue mimicking phantoms, ex vivo tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils were evaluated to enable active catheter-tracking and prescription of thermometry slice positions. Interstitial and intraluminal ultrasound applicators could be used to ablate (t43>240min) tumors measuring 2.3-3.4 cm in diameter when powered with 20-30 W/cm2 at 7 MHz for 5-10 min. Endoluminal applicators with planar and curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to 20-25 mm deep from the stomach wall within 5 min. POC devices were fabricated and successfully integrated into the MRI environment with catheter tracking, real-time thermometry and closed-loop feedback control.
    No preview · Article · Feb 2013 · Proceedings of SPIE - The International Society for Optical Engineering
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    ABSTRACT: Irreversible electroporation (IRE) has shown promise for ablation of lesions in proximity to vital structures in the preclinical and now clinical setting. Studies of patients undergoing IRE for treatment of metastatic colorectal cancer to the liver were reviewed for patient and tumor characteristics, treatment-related complications, and local recurrence-free survival (LRFS) for ablated lesions. LRFS was calculated according to the Kaplan–Meier method, with secondary analyses stratified by procedural approach (laparotomy, laparoscopy, percutaneous) and tumor histological characteristics. Initial IRE success has been achieved in 95 % of treatments. The LRFS rates at 3, 6, and 12 months were 97.4 %, 94.6 %, and 59.5 %. There was a trend toward higher recurrence rates for tumors larger than 4 cm (hazard ratio 3.236, 95 % confidence interval 0.585-17.891; p = 0.178). IRE is a safe and effective treatment for metastatic colorectal cancer to the liver near vital structures. Continued evaluation is needed to determine optimal probe design and techniques.
    No preview · Article · Jun 2013 · Current Colorectal Cancer Reports
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