SAN DIEGO – A surgical technique for ablating pancreatic tumors improved overall survival for individuals with locally advanced pancreatic cancer when combined with optimized chemotherapy and radiation therapy.
Pancreatic cancer is the fourth-leading cause of cancer death in the United States. It often is not detected until disease is advanced, with a 5-year survival rate of less than 6%. Further, the pancreas has tight anatomic association with such major vessels as the superior mesenteric artery and the celiac trunk, meaning that the primary tumor of advanced pancreatic cancer is difficult to resect with conventional surgical techniques.
Dr. Robert Martin
Irreversible electroporation (IRE) is an Food and Drug Administration–approved surgical technique that delivers multiple targeted high-voltage charges of short duration – 70-90 microseconds – to tumor tissue. Cell death occurs slowly by apoptosis over 6-8 weeks, thus avoiding a large inflammatory response and allowing macrophages to help clear cell debris, Dr. Robert Martin of the University of Louisville (Ky.) said at the annual meeting of the American Surgical Association.
Previous work by Dr. Martin and others showed IRE to be safe for appropriately selected patients with locally advanced pancreatic cancers. For this study, Dr. Martin and his colleagues maintained an approved, prospective soft-tissue ablation registry for patients (n = 200; median age, 62 years) with locally advanced pancreatic cancer treated in participating centers from 2010 to 2014.
Participating patients received chemotherapy, radiation, or both as initial treatment according to the protocol of individual institutions. At 4-6 weeks after completing initial treatment, patients were assessed using a triple-phase CT scan and tumor markers. Those who showed no metastatic disease and whose tumors were stable were considered for IRE. Patients were generally well nourished and without multiple comorbidities.
The IRE procedure was performed with (n = 50) or without (n = 150) conventional tumor resection, depending on surgeon judgment. Complete tumor ablation occurred in all 50 patients who received resection and marginal IRE and in 148 of 150 who received IRE alone. Of the patients who had surgery, 20 experienced a total of 49 complications; of those who had IRE alone, 54 had a total of 100 complications. The overall grade of complications was 2, and mean length of stay was 6 days.
The disease progressed in 29% of the 200 patients, with a median overall survival of 28.3 months for those who had resection and IRE and 23.2 months for those receiving IRE alone. Patients receiving standard care survived a median of 13 months (P = .01).
IRE had a reasonable level of safety and demonstrated excellent local control of tumor growth, noted discussant Dr. Jeffrey Drebin, chair of the department of surgery at Penn Medicine, Philadelphia. He asked, however, whether the study would have benefited from an intention-to-treat analysis, since not all patients with locally advanced disease will be candidates for optimized chemotherapy.
Dr. Martin noted that, as better neoadjuvant treatments have come along, “we are taking far more patients to the operating room … because we are rewarded by being able to resect their tumors.”
He called for “cautious optimism” regarding the role of IRE. The next step should include validation of the study results in the United States, first through a single-arm study and then in a randomized controlled trial comparing IRE to radiation therapy. Full assessment of efficacy also will hinge on identifying appropriate imaging techniques for precise documentation of tumor response.
An attitude of “persistent nihilism” in treating pancreatic cancer can pose a barrier to the willingness of patients and providers to try multimodality, aggressive treatment, he said. “Precise management of locally advanced pancreatic cancer with trimodality treatment can lead to improvement.”
Dr. Martin reported compensation from Angiodynamics. The other authors reported no disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.