SIR FOUNDATION RESEARCH FORUM by Derek West, MD, MS


tends to conserve vital structures such as blood vessels within the ablation zone. This occurs primarily because the collagen and elastic matrices within these structures are unaffected by IRE[5].


Currently, IRE has been used in ablative therapies in liver, kidney, lung, prostate and pancreas. The use of IRE in pancreatic adenocarcinoma is particularly promising, as these patients have few treatment options. In 2012, Narayanan et al published a retrospective review of CT-guided percutaneous IRE treatment of 14 patients with unresectable pancreatic adenocarcinoma. For this cohort of patients, the event-free survival (EFS) was 6.7 months, and the 6 month overall survival was 70 percent. Compared to the EFS of metastatic disease patients were removed, the EFS of localized disease patients was significantly longer. No severe complications were observed [6]. Although it is a small cohort, this study demonstrated acceptable safety and efficacy of the procedure. Further, in the largest retrospective PDAC IRE study to date, Martin et al examined the 90-day outcomes, local failure and overall survival. IRE was successfully performed in all patients. Thirty-seven percent of patients sustained complications, with a median grade of 2 (range, 1–5). Median length of stay was 6 days (range, 4–36 days). With a median follow-up of 29 months, 6 patients (3 percent) experienced local recurrence. Median overall survival was 24.9 months (range: 4.9–85 months) [7].


More recent electroporation work has suggested that reversible and irreversible electroporation may be synergistic in cancer therapy. Electrochemotherapy (ECT) is the administration of chemotherapy during electroporation. Similar to gene therapy, the goal of ECT is to increase the intracellular uptake of chemotherapeutic agents. Since the effective electrical field strength experienced by a cell during electroporation is distance dependent,


tumor cells that are far enough away from the electrode site do not receive lethal field strength doses. As a result, the treatment area is limited and micro-metastases may not be treated, leading to tumor recurrence. However, these cells may receive reversible level electroporation, sensitizing them to chemotherapeutics. Thus, the combination of electroporation and chemotherapy could work synergistically to destroy cancer cells.


Since the first clinical study on electrochemotherapy was published in 1991, ECT in cutaneous cancers has been reported as highly effective [8–11]. As such, ECT is routinely used in Europe in the treatment of cutaneous and subcutaneous tumors. More recently, electrochemotherapy has been used successfully for liver metastases and in PDAC. While it has not been fully validated, there is strong evidence that ECT will become a clinical treatment option for our oncology patients in the near future.


In summary, electroporation has demonstrated itself to be more than just another ablative technique. It has the potential to shift the paradigm of interventional oncology ablative treatment. Whether it is used in IRE or in ECT, we have only begun to explore its uses and potentials.


References


1. Kotnik T, et al., Electroporation-based applications in biotechnology. Trends Biotechnol, 2015. 33(8): 480–8.


2. Neumann E, et al., Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J, 1982. 1(7): 841–5.


3. Davalos RV, Mir IL, and Rubinsky B, Tissue ablation with irreversible electroporation. Ann Biomed Eng, 2005. 33(2): 223–31.


Electroporation RELATED RESOURCES


4. Rubinsky B, Irreversible electroporation. Series in biomedical engineering,. 2010, Berlin: Springer. xiv, 312


5. Yu H and Burke CT, Comparison of percutaneous ablation technologies in the treatment of malignant liver tumors. Semin Intervent Radiol, 2014. 31(2): 129–37.


6. Narayanan G, et al., Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma. J Vasc Interv Radiol, 2012. 23(12): 1613–21.


7. Martin RC, 2nd, et al., Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation: Safety and Efficacy. Ann Surg, 2015. 262(3): 486–94.


8. Mir LM, et al., [Electrochemotherapy, a new antitumor treatment: first clinical trial]. C R Acad Sci III, 1991. 313(13): 613–8.


9. Mali B, et al., Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol, 2013. 39(1): 4–16.


10. Escoffre JM and Rols MP, Electrochemotherapy: progress and prospects. Curr Pharm Des, 2012. 18(23): 3406–15.


11. Matthiessen LW, et al., Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncol, 2012. 51(6): 713–21.


SPRING 2016 | IR QUARTERLY 19


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