Sequential Irreversible Electroporation for Locally Advanced Pancreatic Cancer

Abstract

Pancreatic cancer is a lethal disease, with locally advanced pancreatic cancer (LAPC) having a dismal prognosis. For patients with LAPC, gemcitabine-based regimens, with or without radiation, have long been the standard of care. Irreversible electroporation (IRE), a non-thermal ablative technique, may potentially prolong the survival of patients with LAPC. In this article, the authors present a case of LAPC of the uncinate process (biopsy proven pancreatic neuroendocrine carcinoma) with duodenal invasion. The patient had a combination of chemotherapy and radiation therapy but was found to have stable disease. He then underwent intra-operative IRE with cholecystectomy, Roux-en-Y gastrojejunostomy and hepaticojejunostomy. He subsequently underwent percutaneous IRE 13 months post open IRE. The patient also completed peptide receptor radionuclide therapy and has been started on Lanreotide. Following combination therapy, the pancreatic tumor showed significant reduction in size, with patient survival at 53 months post-diagnosis at the time of writing.

Pancreatic cancer is a highly lethal disease, with locally advanced pancreatic cancer (LAPC) having a dismal prognosis. Approximately 30% of patients present with LAPC, defined as greater than 180° circumference tumor encasement of the superior mesenteric or celiac artery, or non-reconstructable venous involvement [1].

For patients with LAPC, gemcitabine-based regimens, with or without radiation, have long been the standard of care. The use of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy has improved survival, but the overall prognosis remains poor. Irreversible electroporation (IRE), a non-thermal ablative technique, may potentially prolong the survival of patients with LAPC [2,3].

A 59-year-old man with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 presented with LAPC of the uncinate process (biopsy proven pancreatic neuroendocrine carcinoma) with duodenal invasion (Figure 1A,B). The patient underwent a combination of chemotherapy and radiation therapy but was found to have stable disease.

The initial plan was for debulking pancreaticoduodenectomy (Whipple’s procedure) with marginal accentuation IRE. Intra-operatively, it was found that there was extensive local invasion. The procedure was thus converted to intra-operative IRE (Figure 2) with cholecystectomy, Roux-en-Y gastrojejunostomy and hepaticojejunostomy. Following open IRE, perforation of the duodenum was encountered (Figure 3), but the patient remained asymptomatic, likely due to gastrojejunostomy. The pancreatic mass 1 year post open IRE showed reduction in size (Figure 4A,B). The patient subsequently underwent percutaneous IRE 13 months post open IRE (Figure 5). The patient also completed peptide receptor radionuclide therapy and has been started on Lanreotide.

Following the combination therapy, the pancreatic tumor showed significant reduction in size (Figure 6A,B), with patient survival at 53 months post-diagnosis at the time of writing.

Given the poor survival of patients with LAPC, even without early distant metastases, several groups are focusing on combining systemic chemotherapy with local ablative therapies. IRE is a non-thermal ablative technique in which high-voltage electrical pulses are applied between needle electrodes. The pulses irreversibly damage the cellular membrane by creating nanopores, inducing programmed cell death [4]. IRE has been shown to be promising in terms of overall survival for patients with LAPC [3]. In addition, percutaneous IRE seems to prolong survival compared with standard of care, as demonstrated in the PANFIRE-2 study [2].

This case demonstrates that sequential IRE may play a role in sustained local tumor response and control for LAPC (pancreatic neuroendocrine carcinoma).