Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study

Abstract

Objective: We aimed to determine the safety and efficacy of irreversible electroporation (IRE) combined with chemotherapy for unresectable pancreatic carcinoma (stage III/IV).

Methods: We prospectively enrolled 54 patients (30 men; median age 61.0 years; range 41-73 years) undergoing IRE with or without chemotherapy for pancreatic cancer between July 2015 and August 2016. Kaplan-Meier estimates were used to analyze progression-free survival (PFS) and overall survival (OS). Safety was assessed based on the occurrence of adverse events.

Results: All patients successfully underwent IRE. Major IRE-related complications were observed in four patients (7.4%). Gastrointestinal hemorrhage only developed in cases undergoing IRE via the open method, and was successfully managed with interventional embolization and/or vascular ligation. Any minor complications in the cases were alleviated within 14 days after symptomatic treatment. Overall, the performance status score decreased from 1.06 to 0.89 at 3 months after IRE (P<0.05). Among those with stage III disease, after a median follow-up of 18.8 months (range 9.6-28.7 months), the median OS from diagnosis was 16.2 and 20.3 months in the IRE and IRE + Chemo groups, respectively. Among those with stage IV disease, after a median follow-up of 13.3 months (range 3.7-23.1 months), the median OS from diagnosis was 11.6 and 13.56 months in the IRE and IRE + Chemo groups, respectively. The OS was significantly poorer in the IRE group than in the IRE + Chemo group (log-rank test, P=0.0398).

Conclusion: Patients with pancreatic carcinoma could benefit from IRE, which improved the OS in certain patients who had also undergone chemotherapy. Although some severe complications were noted, IRE was generally well tolerated.

Keywords: ablation; irreversible electroporation; overall survival; pancreatic carcinoma; progression-free survival.

Figure 1

Flowchart for the selection of the open vs percutaneous approach for irreversible electroporation ablation. Abbreviation: CT, computed tomography.

Figure 2

A 70-year-old woman with T4N1M0, stage III, pancreatic head and neck carcinoma. Notes: Enhanced computed tomography shows a pancreatic tumor measuring 6.9×4.8 cm (A, B). Irreversible electroporation (IRE) is performed (C, D). At 3 months after IRE, the tumor has shrunk to 3.5×2.1 cm, and vascular retention is noted (E, F). The red arrows indicate the tumor and the blue arrows indicate the IRE probes.

Figure 3

A 60-year-old man with T4N1M0, stage III, pancreatic head carcinoma. Notes: At 21 days after irreversible electroporation treatment, enhanced computed tomography shows a low-density, liquefied, necrotic area inside the tumor and a high- density shadow in the stomach and duodenum (A). Celiac artery angiography shows no obvious signs of active bleeding (B). Subsequent gastroscopy shows gastroduodenal artery rupture, and surgical ligation of the blood vessels is performed to stop the bleeding (C).

Figure 4

A 59-year-old man with T4N1M1, stage IV, pancreatic body carcinoma. Notes: Portal vein embolization is noted 9 days after irreversible electroporation (IRE). Computed tomography scans show the appearance of portal vein thrombosis (blue arrows) before (A) and after (B) IRE.

Figure 5

Error bar chart showing the performance status (PS) score before and after irreversible electroporation (IRE). Note: *Significant difference (P<0.05).

Figure 6

Kaplan–Meier survival curves showing OS from diagnosis in patients with stage III (A) and IV disease (B), as well as PFS from diagnosis in patients with stage III (C) and IV disease (D). Abbreviations: Chemo, chemotherapy; IRE, irreversible electroporation; OS, overall survival; PFS, progression-free survival.