In this guest commentary, Marcovalerio Melis, MD, FACS, discusses irreversible electroporation for locally advanced pancreatic cancer, following a presentation on the topic delivered at the Gastrointestinal Cancers Symposium by Robert C.G. Martin, MD, PhD, FACS, from University of Louisville. Melis is an associate professor of surgery at NYU Langone's Perlmutter Cancer Center and serves as chief of surgical oncology at New York Harbor Healthcare System VAMC.
Radical resection remains the only treatment with curative intent for malignancy of the hepato-pancreato-biliary. Unfortunately, pancreatic cancer is resectable in only about 10% to 20% of the cases. The vast majority of those malignancies present instead at a locally advanced stage, where either metastases to other organs or invasion/proximity of the tumor to vital structures prevent resection with negative margins.
Of the nonresectable pancreatic cancers, nearly half present with involvement of the celiac axis or the superior mesenteric artery, which preclude curative treatment. Locally advanced unresectable pancreatic cancer is associated with poor prognosis (median overall survival about 12 months) despite use of chemotherapy and/or conventional radiation therapy.
Even many of those patients who are potentially candidates for surgery will present with tumors that at time of diagnosis are abutting mesenteric or celiac vessels. Those tumors, defined as “borderline resectable,” are at high risk for resection with positive microscopic margins. For this reason, borderline resectable cancers are treated with chemotherapy and/or radiation therapy prior to attempting radical resection. Even after neoadjuvant treatment, however, risk for positive resection margins remains significant.
At this time, there is a relevant need for alternative treatments of pancreatic cancer not amenable to radical surgical treatment.
Conventional thermal ablation techniques (radiofrequency and microwave) rely on the indiscriminate use of thermal energy to induce necrosis of tumor cells, a process that can result in damage to nearby structures including blood vessels, bile ducts and nerves. In addition, the blood flow of large vessels creates a heat sink effect that severely inhibits the ability to ablate cancer cells in the vicinity of large vessels. These limitations are especially relevant to the malignancies of the pancreas, which typically lie immediately adjacent to the superior mesenteric vessels, the portal vein and the common bile duct.
Furthermore, the use of ablative therapies in the pancreas has largely been avoided altogether due to the possibility of thermal injury–induced pancreatitis.
Irreversible electroporation (IRE) is a novel ablation technique that utilizes targeted delivery of high-voltage millisecond electrical pulses resulting in permanent disruption of the cellular membranes and subsequent apoptosis. This process leads to cell death, but does not injure the extracellular matrix, thus allowing cellular tumor ablation while preserving structural components of tissues; therefore, collagen-based structures such as vessels or the pancreatic duct are not disrupted.
Furthermore, because IRE is not based on thermal damage of cancer cells, the heat-sink phenomenon is not a concern, and even lesions abutting large vessels can be ablated with radical intent. Preliminary studies on swine and then humans have shown the feasibility and safety of this procedure on liver and pancreas, with no damage of major vessels and pancreatic duct, and no incidence of pancreatitis.
IRE could be an alternative therapy when neither surgery nor traditional ablation can be used for tumors of the pancreas. IRE may offer an additional treatment option to patients that otherwise would hold no hope for long-term survival and would be traditionally treated with palliative intent with external radiation or systemic chemotherapy. Until recently, there has been a lack of data on early outcomes (eg, periprocedural morbidity and mortality rates, effectiveness of ablation) and long-term survival of patients with nonresectable pancreatic cancer treated with IRE.
During the recent ASCO Gastrointestinal Cancers Symposium in San Francisco, Martin presented his experience with IRE, a technique of which he has been a pioneer. He has developed a new clinical algorithm that includes use of IRE in both patients with borderline resectable and patients with unresectable pancreatic cancer (see Figure 1).
Figure 1: Marcovalerio Melis, MD, FACS; reprinted with permission.
For patients with unresectable pancreatic cancer, IRE is used as the main treatment modality (“in situ” ablation). For patients with borderline resectable pancreatic cancer, IRE can be used in addition to surgical resection to “sterilize” from any remnant cancer cells the peripancreatic structures and connective tissues that are not removed by the surgeon.
Martin had previously shown that in 54 patients with locally advanced pancreatic cancer, addition of IRE can improve local progression-free (14 vs. 6 months), distal progression-free (15 vs. 9 months), and OS (20 vs. 13 months) when compared with chemoradiation alone.
Martin has now accumulated multi-institutional data on 200 patients with locally advanced pancreatic cancer. In this new report, OS was 28.3 months for patients with borderline resectable pancreatic cancer, and 23.2 months in patients with unresectable pancreatic cancer. Those numbers compare favorably with the survival of patients treated with chemoradiation alone, which is 13 months in historical controls.
In summary, IRE appears to be a very promising technique that may be used as part of a multidisciplinary treatment strategy in properly selected patients with pancreatic cancer. The initial favorable results of IRE presented by Martin need to be validated in upcoming randomized trials.
Currently, IRE is offered in few tertiary referral centers, including the Perlmutter Cancer Center at NYU Langone.
Martin RCG. “Innovative Surgical Option: Irreversible Electroporation.” Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.
Disclosures: Melis reports no relevant financial disclosures.