This document addresses use of the NanoKnife® Oncobionic System (AngioDynamics® Inc., Fremont, CA) which is classified by the U.S. Food and Drug Administration (FDA) as a Class II electrosurgical cutting and coagulation device. This document exclusively addresses all uses of irreversible electroporation (IRE), as a specific form of tissue ablation.
Note: For information related to other ablative techniques for cancer treatment, please see:
Investigational and Not Medically Necessary:
Irreversible electroporation (IRE) is considered investigational and not medically necessary for all indications, including, but not limited to, ablation of soft tissue or of solid organs, such as the liver and pancreas.
The NanoKnife Oncobionic System is a low energy, direct current, nonthermal ablative device system for use in performing a minimally invasive procedure referred to as "irreversible electroporation (IRE)." The NanoKnife received FDA clearance, as substantially equivalent to prior Oncobionic Systems, also manufactured by AngioDynamics, Inc., as a Class II device for, "The surgical ablation of soft tissue" (FDA, 2011).
Use of the NanoKnife Oncobionic System involves the process of using brief and controlled electric pulses to open microscopic pores in a targeted area. By increasing the number, strength, and duration of electric pulses, electroporation can be made permanent or irreversible. It is purported by the manufacturer, AngioDynamics, Inc., that IRE technology allows for extreme precision in targeting soft-tissue cells of interest while blood vessels and other sensitive structures in the area remain functional. However, to date, there is very limited scientific evidence to demonstrate the safety or efficacy of this technology. The first such procedure was performed at Stony Brook University Medical Center (New York) in December 2009 to treat pancreatic cancer.
The published evidence to date has consisted of limited studies using theoretical calculations, in vitro experiments, and statistical models to examine potential uses of this technology (Goldberg, 2010; Miller, 2005; Neal, 2009; Shafiee, 2009). One single-center, prospective, nonrandomized cohort study was performed to investigate the safety of IRE for tumor ablation in 38 humans with advanced malignancy of the liver, kidney, or lung. Transient ventricular arrhythmia occurred in 4 subjects, and electrocardiographically (ECG) synchronized delivery was used subsequently in the remaining 30 participants with occurrence of two further arrhythmias (supraventricular tachycardia and atrial fibrillation). One subject developed obstruction of the upper ureter after IRE. One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension. There was no other evidence of adjacent organ damage related to the electroporation. Only 30-day outcomes were reported. Although not a primary aim of this preliminary study, complete target tumor ablation verified by computed tomography (CT) was achieved in 46 of the 69 tumors treated with IRE (66%). Most treatment failures occurred in renal and lung tumors. Biopsy in 3 subjects showed coagulative necrosis in the regions treated by IRE. The authors concluded, "IRE appears to be safe for human clinical use provided ECG-synchronized delivery is used. Comparative evaluation with alternative ablative technologies is warranted" (Thomson, 2011).
There have been clinical trials of IRE; one is the Pilot Study of Irreversible Electroporation (IRE) to Treat Early-Stage Primary Liver Cancer (HCC), which was sponsored by the manufacturer, AngioDynamics, Inc., and is currently listed as, "Completed" as of November 7, 2016. However, to date, no articles have been published about this study (NCT01078415). Another study listed on 'Clinical trials.gov" indicates this manufacturer-sponsored study is also "Completed," but nothing has been published regarding trial results (NCT01369420). There is currently inadequate evidence in the published literature to support the safety and efficacy of this technology or to demonstrate how treatment with this surgical device will impact clinical outcomes for any condition or indication. Recent publications of small retrospective chart reviews and prospective pilot studies of IRE in the treatment of advanced malignancies of the pancreas and liver have reported limited short-term improvements with high rates of adverse events and trends toward recurrence in larger tumors (over 4 cm) also noted (Cannon, 2013; Kingham, 2012; Martin, 2012; Moir, 2014). A small prospective, single-arm, phase II clinical trial was conducted at two centers to evaluate the safety and effectiveness of IRE as a treatment for lung cancers which failed to meet primary and secondary endpoints. The expected effectiveness was not met at interim analysis, and the trial was stopped prematurely after inclusion of 23 subjects (Ricke, 2015).
The NanoKnife Oncobionic System received initial clearance from the U.S. Food and Drug Administration (FDA) on November 21, 2006 as a tissue ablation system indicated for surgical ablation of soft tissue, including cardiac and smooth muscle (FDA, 2006). Subsequent FDA clearance clarified the indications, "For the surgical ablation of soft tissue" (FDA, 2008). According to the FDA information available online, "It has not received clearance for the therapy or treatment of any specific disease or condition" (510[k] Number: K080376, 2008). The NanoKnife System is classified by the FDA as an electrosurgical cutting and coagulation device (FDA, 2011).
On January 21, 2011 the FDA Center for Devices and Radiological Health (CDRH) issued a warning letter to the manufacturer, AngioDynamics, Inc. regarding the NanoKnife Oncobionic System branding and labeling indications listed on the manufacturer's website. The FDA requested that the words, "treat," "treatment," and "therapy" be removed and replaced with the word "ablation" throughout the labeling for the device, since the FDA clearance is not for any specific disease or condition. The FDA also requested that a precise definition of "Irreversible Electroporation or IRE" be provided, since this term was not part of the initial FDA application (FDA, 2011). The information currently available on the FDA web site for the NanoKnife no longer refers to the terms, "Irreversible Electroporation or IRE" and identifies the device as, "A low energy, direct current, non-thermal ablation device" (FDA, 2011).
Electroporation: The process of using brief and controlled electric pulses to open microscopic pores in a targeted area. By increasing the number, strength, and duration of electric pulses, electroporation can be made permanent or irreversible (IRE). After IRE, the pores in the cells remain open permanently with resultant microscopic damage to cells.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services are Investigational and Not Medically Necessary:
|For the following unlisted codes, when specified as ablation by irreversible electroporation:|
|32999||Unlisted procedure, lungs and pleura|
|47399||Unlisted procedure, liver|
|48999||Unlisted procedure, pancreas|
|53899||Unlisted procedure, urinary system|
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
Ablation, Soft Tissue
Soft Tissue Ablation
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Reviewed||08/03/2017||Medical Policy & Technology Assessment Committee (MPTAC) review. The Rationale and References sections were updated.|
|Reviewed||08/04/2016||MPTAC review. The Rationale and References were updated. Removed ICD-9 codes from Coding section.|
|Reviewed||08/06/2015||MPTAC review. The Rationale and References were updated.|
|Reviewed||08/14/2014||MPTAC review. The Rationale and References sections were updated.|
|Reviewed||08/08/2013||MPTAC review. The Rationale, Background and References were updated.|
|Revised||08/09/2012||MPTAC review. The document was revised to make clear that all uses of IRE are addressed and considered investigational and not medically necessary. Document was retitled: Irreversible Electroporation (IRE). The Scope, Rationale and References were updated.|
|New||08/18/2011||MPTAC. Initial policy development.|