Irreversible electroporation of pancreatic adenocarcinoma

Sammanfattning: Pancreatic cancer (PC) is a severe diagnosis with poor prognosis. Radical surgery is the only treatment that can possibly lead to a cure, and even with surgery, the 5-year survival is only 20%–25%. The majority of patients cannot be resected due to metastases or having a tumour that is too advanced locally (LAPC) with encasement of blood-vessels.Short electrical pulses can change the cell membrane, creating reversible pores in it. With a higher current, the pores become permanent, resulting in irreversible electroporation (IRE). This leads to specific cell death, with the chance to save surrounding scaffold material, such as the walls of blood vessels and bile ducts. This led to the theory that IRE might be suitable for treating LAPC.In Paper I, we found that IRE can be safely performed percutaneously with ultrasound guidance in humans with PC, with promising efficacy, since one of the five patients included was downstaged due to the IRE and could be surgically resected. In Paper II, which is an extension of Paper I, we treated 24 patients with LAPC (3 were also included in Paper I) who had received chemotherapy and, after IRE, stable disease was seen. Median overall survival was 17.9 months. Eleven patients had some form of complication, but we still concluded that IRE is reasonably safe in LAPC patients, with promising efficacy. In Paper III, we chose to treat LAPC with IRE followed by adjuvant chemotherapy. We compared the overall survival of our patients with those with LAPC in the National Quality Registry for Pancreatic and Periampullary Cancer. No significant survival gain could be seen in the group that received IRE compared to the registry group (13.3 months versus 9.9 months, p=0.511). In the IRE group, there were six major complications and we found no support for using IRE in this setting. Paper IV examines the response on the tumour marker CA19-9 in PC treated with IRE. We found 35 patients suitable for this analysis. The hypothesis that IRE would lower the CA19-9 value could not be proven. In fact, the CA19-9 was slightly higher one month after IRE (282 U/ml versus 315 U/ml). However, the 25th percentile of patients with the best CA19-9 response had a better survival (p=0.01) compared to the 25th percentile with the worst response, indicating that CA19-9 can be used as a prognostic marker after IRE in PC.