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: 3.94). 11/2012; DOI: 10.1245/s10434-012-2736-1
Source: PubMed

ABSTRACT BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Irreversible electroporation (IRE) is an ablation technique that is being investigated as a potential treatment of pancreatic cancer. However, many of these patients have a metallic stent in the bile duct, which is recognized as a contraindication for IRE ablation. We report a case in which an IRE ablation in the region of the pancreatic head was performed on a patient with a metallic stent which led to severe complications. After the treatment, the patient suffered from several complications including perforation of the duodenum and transverse colon, and bleeding from a branch of the superior mesenteric artery which eventually lead to her death. Therefore, we believe it is important to be aware of this if an IRE ablation close to a metallic stent is considered.
    12/2014; 3(11):2047981614556409. DOI:10.1177/2047981614556409
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Complete tumor extirpation (R0 resection) remains the best possibility for long-term survival in patients with pancreatic adenocarcinoma. Unfortunately, approximately 80% of patients are not amenable to resection at diagnosis either because of metastatic (40%) or locally advanced disease (40%). Recent reports of irreversible electroporation (IRE), a high-voltage, short-pulse, cellular energy ablation device, have shown the modality to be safe and potentially beneficial to prognosis. IRE to augment/accentuate the margin during pancreatic resection for certain locally advanced pancreatic cancers has not been reported. Methods Patients with locally advanced/borderline resectable pancreatic cancer who underwent pancreatectomy with margin accentuation with IRE were followed in a prospective, institutional review board–approved database from July 2010 to January 2013. Data regarding local recurrence, margin status, and survival were evaluated. Results A total of 48 patients with locally advanced pancreatic/borderline cancers underwent pancreatectomy, including pancreatoduodenectomy (58%), subtotal pancreatectomy (35%), distal pancreatectomy (4%), and total pancreatectomy (4%), with IRE margin accentuation of the superior mesenteric artery and/or the anterior margin of the aorta. Most patients had undergone induction therapy with 33 patients (69%) receiving chemoradiation therapy and 18 patients chemotherapy for a median of 6 months (range, 4–13) before resection. A majority (54%) required vascular resection. A total of 9 patients (19%), sustained 21 complications with a median grade of 2 (range, 1–3), with a median duration of stay of 7 days (range, 4–58). With median follow-up of 24 months, 3 (6%) have local recurrence, with a median survival of 22.4 months. Conclusion Simultaneous intraoperative IRE and pancreatectomy can provide an adjunct to resection in patients with locally advanced disease. Long-term follow-up has demonstrated a small local recurrence rate that is lower than expected. Continued optimization in multimodality therapy and consideration of appropriate patients could translate into a larger subset that could be treated effectively.
    Surgery 10/2014; 156(4):910–922. DOI:10.1016/j.surg.2014.06.058 · 3.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Irreversible electroporation (IRE) ablation uses a series of brief electric pulses to create nanoscale defects in cell membranes, killing the cells. It has shown promise in numerous soft-tissue tumor applications. Larger voltages between electrodes will increase ablation volume, but exceeding electrical limits may risk damage to the patient, cause ineffective therapy delivery, or require generator restart. Monitoring electrical current for these conditions in real-time enables managing these risks. This capacity is not presently available in clinical IRE generators.
    CardioVascular and Interventional Radiology 08/2014; DOI:10.1007/s00270-014-0961-7 · 1.97 Impact Factor