Further research into the use of percutaneous irreversible electroporation (IRE) in the treatment of pancreatic cancer is essential, according to Govindarajan Narayanan, chief of Interventional Oncology at the Miami Cancer Institute, and professor of Radiology at Florida International University (USA). He made this call at the Spectrum conference (1–4 November, Miami, USA).
“We now see a signal towards possible survival benefits, so a registry and probably a randomised controlled trial to really understand the role of IRE in pancreatic cancer is definitely an unmet need,” he told conference attendees. He added that a comprehensive mechanism for follow-up criteria and protocols for locally advanced pancreatic cancer patients who have had radiotherapy should also be developed and validated.
Until recently, treatment options for pancreatic cancer were surgery, for which only 10–20% of patients will qualify, radiation or chemotherapy, or a palliative treatment algorithm. Narayanan assessed the role of percutaneous IRE to see whether it can be performed in a minimally invasive and reproducible fashion, and what its impact has been on the signal to survival benefit. “After using this technology in the pancreas for the last nine years,” he said, “there are a few things we have learned.”
He ran through the trials to date that have looked at the safety and efficacy of the procedure. The first two he cited were from his own centre. In 2012, his group did a retrospective series on 14 patients looking at percutaneous IRE for down-staging and control of unresectable pancreatic adeonocarcinoma. They followed this with a further retrospective study in 2017, on percutaneous image guided IRE for the treatment of unresectable locally advanced pancreatic adenocarcinoma. This single centre study of 50 patients, all of whom had biopsy-proven unresectable pancreatic cancer, assessed the safety profile, with a secondary objective of determining overall survival. All patients had had chemotherapy, and 60% had also had prior radiation therapy; follow-up was computed tomography (CT) at one month and every three months thereafter.
The median time from diagnosis to IRE was 11.6 months, and there were serious adverse events in 10 of 50 patients (20%)—seven suffered abdominal pain, and one each had pancreatitis, sepsis, and a gastric leak. Narayanan described the finding of 27 months from time of diagnosis and 14.2 months from IRE as “a healthy median overall survival”. There were no treatment-related deaths, and no 30-day mortality.
“We did a multivariate analysis to see if there was any different predictor that helped with overall survival. We found that tumour size <3cm had significantly longer overall survival than tumour sizes that were >3cm.”
Also in 2017, Hester Scheffer (Amsterdam, The Netherlands) et al published the findings of the PANFIRE study, which looked at ablation of locally advanced pancreatic cancer with percutaneous IRE. “The purpose of this study was to investigate the safety,” explained Narayanan, “but also to look at the quality of life, pain perception and efficacy in terms of time to local progression, event free survival, and overall survival. It found that percutaneous IRE for locally advanced cancer is generally well tolerated, although there were some major adverse events. And preliminary survival data were encouraging.”
An Italian study from Maria Belfiore (Naples, Italy) et al in 2017 outlined the preliminary experience of using percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in 20 patients with locally advanced pancreatic cancer. No major complications occurred—although two patients died three and four months after treatment, this was due to rapidly progressive disease. In the remaining 18 patients, six-month imaging follow-up showed a volumetric decrease in the lesion size of 42.8%, and three patients underwent R0 resection. The investigators concluded that IRE followed by chemotherapy is safe, feasible, and effective in producing short-term control of locally advanced pancreatic adenocarcinoma (LAPC) with a possible down-staging effect to resectable lesions.
In the UK, Edward Leen (London, UK) et al conducted a retrospective review from 2011 to 2016 of 75 patients who had unresectable pancreatic carcinoma and underwent percutaneous IRE after chemotherapy using computerised tomography guidance under general anaesthesia.
Post-procedural immediate and 30-day mortality rates were both zero, and all grade adverse events were 25%. The median in-patient stay was one day, described by Narayanan as “typical of percutaneous IRE; you have a significant advantage there, one to one and a half days stay in the hospital.”
The median overall survival and progression free survival rates post-IRE for LAPC were 27 and 15 months, respectively—“very similar to other results that have been achieved”.
Narayanan pointed out: “Prospective and retrospective studies have established the safety of this procedure, and studies from different centres around the world have shown that this technique is reproducible, with a positive signal towards survival benefit. The US Food and Drug Administration has recently provided a breakthrough designation for IRE in pancreatic cancer.”
He said that further developments would follow, and promised: “We are hoping to have more exciting news in this space very soon.”