AngioDynamics IRE Slide Deck Outline
ICD-10 Coordination and Maintenance Committee Meeting

Slide 1:

ICD-10 Coordination and Maintenance Committee Meeting

Irreversible Electroporation
A Treatment for Pancreatic and Liver Tumors

March 18, 2015

Presented by: Robert C.G. Martin, II, MD, PhD, FACS

Slide 2: 

Irreversible Electroporation 
A Treatment for Pancreatic and Liver Tumors

Image of University of Louisville.

March 18th, 2015
Disclosures: Paid consultant for AngioDynamics

Robert C.G. Martin, II, MD, PhD, FACS
Sam and Lolita Weakley Endowed Chair in Surgical Oncology Director, Division of Surgical Oncology Director of the Upper GI and HPB Multi-Disciplinary Clinical Professor of Surgery Academic Advisory Dean University of Louisville

Slide 3:

Agenda
 Coding Issue
 Incidence & Statistics related to Pancreatic and Liver Cancer
 About Irreversible Electroporation as a treatment for Pancreatic and Liver Cancer
 Rationale for new ICD-10-PCS code
 ICD-10-PCS Options
 New Technology Add On Payment Application
 Questions / Answers / Discussion

Slide 4:

Irreversible Electroporation (IRE)

Issue:
 The Current ICD-10-PCS codes do not identify the specific technique that induces tumor cell membrane porosity thereby causing auto-programmed cancer cell death (i.e., apoptosis)
 New Technology Add on Payment will be applied for in 2015 for consideration in 2017
 Request new ICD-10-PCS code as soon as code freeze lifts
 Avoid delays in tracking hospital cost and utilization data

Slide 5:

About Pancreatic and Liver Cancer

Slide 6:

Pancreatic Cancer is Projected to Become the 2nd Leading Cause of Cancer Death by 2020!

Pancreatic cancer is the fourth most common cause of death by cancer, but is on the rise.
Pancreatic cancer is projected to become the 2nd leading cause of cancer death in the US by 2020.

The table illustrates the projected cancer deaths in thousands.  The table compares breast, colorectal, prostate, lung and pancreas and demonstrates that pancreatic cancer deaths are on the rise. 

Source: Siegel et al  CA Cancer J Clin 2013; Pancreatic Cancer Action Network 2012
Slide 7:
Pancreatic Cancer
The first table illustrates the 5 year relative survival (%) SEER program, 2002-2008, both sexes by race and cancer site.  Pancreas has the lowest 5 year relative survival % of any cancer site presented on the table.
The second table illustrates the partition of trend in death rates for the time period 2000- 2009, all races, both sexes.  While the death rate for most cancers has decreased over the time period shown, the death rate for pancreatic cancer has increased by 75%
Slide 8:

Pancreatic Cancer 

Pancreatic Cancer Biology

 45,000 cases diagnosed in 2012
 10-20% patients will present with Resectable Stage II disease
 95% of these resected patients will recur in the next 5 years after their resection
 Most will relapse with metastatic disease 
 Approx 30% will recur with only local disease
 Median interval: primary surgery and diagnosis recurrence 10.4 months (range 2.0-19.2 )
 30-35% patients present with Locally Advanced Stage III disease
 Devastating disease with high mortality rate and overall 5 year survival rate lower than 5%
 Recently, an autopsy series of patients with pancreatic cancer identified 30% who succumbed to locally destructive disease without evidence of progression at distant sites
 Historically and nihilistically, with little foundation, little evidence, and with limited success chemo-radiotherapy alone has been and remains a component of LAPC therapy subsequent to a few small studies in the 1980s that used ineffective systemic therapies and older radiation techniques

Slide 9:
Liver Cancer
Liver Cancer Treatment Options
 Complete surgical resection remains the most effective therapy for hepatic malignancy
 Delays in diagnosis or poor underlying liver function mean that the number of patients who are candidates for this potentially curative approach is relatively small
 In patients with HCC: 3040% patients eligible for surgical resection
 Non-surgical candidates with hepatic tumors may receive a liver directed therapy
 Radiofrequency ablation (RFA), ethanol ablation, laser ablation, cryoablation, high intensity focused ultrasound (HIFU), microwave ablation, and stereotactic body radiation therapy

Slide 10:

Liver Cancer

 Thermal ablative technologies limitations: size & location limited the use and effectiveness of these modalities
 RFA studies have demonstrated that the rate of complete tumor necrosis falls below 50% when there are vessels larger than 3mm abutting the tumor, a consequence of the heat sink effect 
 Lesions in a sub capsular location or in close proximity to the gallbladder demonstrate similar difficulty in achieving complete ablation. 
 Similar limitations around safety have also been demonstrated with the other thermal modalities in relation to lesions in proximity to vital structures (i.e., major bile ducts, portal vein, and hepatic veins).

Slide 11:

Irreversible Electroporation (IRE) as a treatment for pancreatic and liver cancers

Slide 12:

Irreversible Electroporation (IRE)

A new treatment modality for locally advanced pancreatic & hepatic tumors
 Series of short, low energy direct current electrical pulses
 Does not rely on heat to ablate tissue
 Creates defects  permanent pores in cell membranes
 Cell death occurs by apoptosis
 This immune mediated cell death allows cellular clearance of debris and creates minimal tissue distortion

Image one illustrates a series of short, low energy direct current electrical pulses
Image two illustrates this immune mediated cell death allows cellular clearance of debris and creates minimal tissue distortion

Slide 13:

Irreversible Electroporation (IRE)

Cell Exposure to Electric Field  Nano Sized Pore Formation
 Exposure to an electric field may result either in permeabilization of cell membrane or its destruction
 Temporary permeabilization can be described as Reversible Electroporation
 Permanent permeabilization can be described Irreversible Electroporation

The image demonstrates a normal liver vs. IRE with Nanopores

Slide 14:

Established Dose Response Curve

The image provides a visual of the dose response curve.  There is also an image of the before and after of a cell membrane. 

Slide 15:

Irreversible Electroporation (IRE)

Comparison of Biological Effects between Thermal Ablation and Irreversible Electroporation (IRE)

The table compares the effects of Thermal Ablation vs. IRE and demonstrates that there are less negative effects when using IRE.

Slide 16:

An IRE System

An IRE System Components
 Generator 
 Single-use disposable electrodes

Features
 19 gauge diameter
 Up to 6 disposable electrodes may be used
 Two electrode lengths available 15cm and 25cm

Image of IRE System  

Slide 17: 

The IRE System

IRE Probe Geometries
 Customizable configurations for various tumor sizes

The images demonstrate the various probe geometries: two probe array, three probe array, four probe array, six probe array.

Slide 18:

Irreversible Electroporation (IRE)

Benefits: Precise Cellular Targeting
 All cells in ablation zone are affected by electrical field- either transiently or permanently
 Fibrous and Collagen Structures are not affected
 Intact adventitia & laminae visible at 2 days with no smooth muscle cells present.
 Endothelium largely repopulates at 2 days.
 Smooth muscle repopulated at 2 weeks.

Image of a diagram showing the cellular layers. 

Slide 19:

Pre-Clinical Data Support IRE is Safe & Effective

Pre-Clinical IRE in Pancreas
 Bower et al  Chronic animal study (14 days)
 No AE, All animals survived, no vascular thrombosis
 Complete ablation
 Charpentier et al  Acute animal study (2 hours)
 No vascular thrombosis  complete ablation
Pre-Clinical IRE in Liver
 Brown et al  Chronic animal study (4 days)
 Optimal probe spacing and number. no AE, effective
 Charpentier et al  Acute animal study
 Safe
Slide 20:

IRE: Established Criteria

Evaluation of learning curve
 Philips et al  IRE of Unresectable Soft Tissue Tumors: learning curve evaluation in the first 150 patients treated
Technical success
 Defined as the ability to successfully deliver all planned accordance with the size and dimension of the lesion
Proximity to critical structures
 Proximity to major vascular/biliary structures or adjacent organs was defined as <5mm in distance
Ablation recurrence
 Persistent viable tumor as defined by dynamic imaging in comparison to pre-IRE scan or tissue diagnosis
Ablation success
 The ability to deliver the planned therapy in the operative room and at 3 months to have no evidence of residual tumor on cross-sectional imaging of treating-teams choice such as CT, MRI or PET (if pre-operative PET avid scan)
Slide 21:

Irreversible Electroporation (IRE)

Current Clinical Use of IRE in the Pancreas
 Treat locally advanced pancreatic cancer (80% use)  Stage III
 Margin accentuation/augmentation therapy (10% use)  Stage IIb
 After patient has undergone appropriate neo-adjuvant therapy
 Treat local recurrent cancer (5% use)
 Metastatic disease to pancreas (5% use)

Slide 22:

Irreversible Electroporation (IRE)

Benefits of IRE in Pancreas
 Can be performed in conjunction with pancreatic resection
 Can be utilized to augment any margin that is considered to be close or positive R1.
 No thermal based modality has demonstrated Safety or Efficacy
 Only current modality that is used is XRT
 Best reported recurrence rate of 4-8%, median OS in Stage III LAPC is 9 months (4-11months)

Slide 23:

Irreversible Electroporation (IRE)

Benefits of IRE in the Liver
 The ability to achieve ablation without damage to surrounding vital structures
 No evidence of heat sink effect despite close proximity to major vascular structures
 No evidence of damage to the portal triad structures
 IRE has a suitable role in the treatment of patients who are less than ideal candidates for current thermal ablation modalities due to tumor location in proximity to vital structures.

Slide 24:

Clinical Experience with IRE for Margin Accentuation

Methods
 Patients with pancreatic cancer who underwent pancreatectomy with margin accentuation with IRE were followed in a prospective IRE approved database from 7/2010 to 7/2013
 Data regarding local recurrence, margin status, and survival were evaluated
Results
 48 patients underwent pancreatectomy
 Pancreaticoduodenectomy (58%), subtotal pancreatectomy (35%), distal pancreatectomy (4%), and total pancreatectomy (4%)
 IRE margin accentuation of the superior mesenteric artery and/or the anterior margin of the aorta
 All patients underwent induction therapy
 25 patients had chemo-radiation therapy, 18 patients had chemotherapy, for a median duration of 6 months (4-13) prior to resection
 A majority (54%) required vascular resection

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Clinical Experience with IRE for Margin Accentuation

Results
 Total of 9 (19%) patients, sustained 21 complications with median grade of 2 (range 1-3)
 Median length of stay of 7 days (range 4-58).
 Median FU of 24 months, 3 (6%) have local recurrence, with a median survival of 23.5 months.
Conclusions
 Simultaneous intra-operative IRE and pancreatectomy can provide an adjunct to resection in patients with locally advanced disease
 Long-term follow up has demonstrated a small local recurrence rate that is far below expected.
 Continued optimization in multi-modality therapy and consideration of appropriate patients could translate into a larger subset that could be effectively treated.

Slide 26:

Clinical Experience with IRE for Stage III LAPC

Image of article from Annals of Surgical Oncology, The Official Journal of the Society of Surgical Oncology. 

Irreversible Electroporation in Locally Advanced Pancreatic Cancer:  Potential Improved Overall Survival

Methods
 Patients with stage III locally advanced pancreatic cancer who underwent IRE for unresectable pancreatic cancer were followed in a prospective IRE approved database from 12/2009 to 10/2010 was evaluated for overall survival and propensity marched to 85 matched stage III patients treated with standard therapy (Chemo or XRT)

Slide 27:

Clinical Experience with IRE for Stage III LAPC

Results
 54 patients underwent IRE successfully
 21 women, 23 men, median age 61 (range 45-80)
 Pancreatic head (35 patients), Pancreatic Body/Neck (19 patients)
 19 patients underwent margin accentuation with IRE, 35 underwent in-situ ablation with IRE
 49 patients (90%) had  pre-IRE chemotherapy alone or chemoradiation therapy for a median duration of 5 months
 40 patients (73%) underwent post-IRE chemotherapy or chemoradiation.  

Slide 28:

Clinical Experience with IRE for Stage III LAPC

Results
 90 day mortality in the IRE patients was 1 (2%)
 Comparing IRE patients to standard therapy, we have seen improvement in:
 Local progression-free survival 
 (14 vs. 6 months, p=0.01)
 Distant progression-free survival 
 (15 vs. 9 months, p=0.02)
 Overall survival 
 (20 vs. 13 months, p=0.03)

The table titled Electroporation in Locally Advanced Pancreatic Cancer demonstrates IRE+chemo/radiation has a longer survival rate than chemo/radiation. 

Slide 29:

Clinical Experience with IRE for Stage III LAPC

Conclusions
 IRE ablation of locally advanced pancreatic tumors remains safe and in the appropriate patient who has undergone standard induction therapy for a minimum of 4 months can achieve greater local palliation and potential improved overall survival compared with standard chemoradiation-chemotherapy treatments

Slide 30:

Image of article from Journal of Surgical Oncology, Safety and Efficacy of Irreversible Electroporation for Hepatic Tumors in Proximity to Vital Structures.

Methods
 Patients undergoing IRE for hepatic tumors were followed on an IRB approved prospective registry over a 2-year period and evaluated for safety and efficacy
 Factors analyzed included patient and tumor characteristics, treatment related complications, and local recurrence free survival (LRFS) for ablated lesions

Slide 31:

Clinical Experience with IRE in Liver

Results
 44 patients underwent 48 total  IRE procedures successfully 
 20 colorectal mets, 14 hepatocellular, and 10 other metastatsis. 
 Five patients had 9 adverse events, with all complications resolving within 30 days
 LRFS at 3, 6, and 12 months was 97.4%, 94.6%, and 59.5%. 
 There was a trend toward higher recurrence rates for tumors over 4 cm 
 (HR 3.236, 95% CI: 0.58517.891; P  0.178).
Conclusions
 IRE appears to be a safe treatment for hepatic tumors in proximity to vital structures. 

Slide 32:

ICD-10-PCS Rationale for Irreversible Electroporation, IRE

 Under Current ICD-10-PCS codes ablation is a term included in the root operation Destruction as, physical eradication of all or a portion of a body part by the direct use of energy, force or destructive agent
 The current ICD-10-PCS codes do not identify the specific technique that induces tumor cell membrane porosity thereby causing auto-programmed cancer dell death (i.e., apoptosis)

Having unique codes to distinctly identify Irreversible Electroporation (IRE) procedures will enable:
 Tracking and measurement of utilization
 Tracking clinically meaningful outcomes measurements
 Clear procedural code option for hospital coders
 Unique codes will help differentiate between Irreversible Electroporation (IRE) and thermal ablative modalities to allow for essential data collection 

Slide 33:

ICD-10-PCS Committee Preliminary Code Options

Option One
Description: Do not create new codes for IRE
Comment:  This option does not enable a means to capture the IRE procedure

Option Two (Selected)
Description: Create qualifier F (IRE) in character 7 of section 0F5to identify IRE versus other destruction techniques.
Comment:  We support this option as this will provide a means to capture the use of IRE.  This option makes sense and is logical as it is within the same root operation as other destructive techniques. 

Option Three
Description: Create new codes in section X New Technology to identify the IRE destruction technique.
Comment:  We do not support this option as there is not enough information on this New Technology option. 

Slide 34:

Clinical Questions

Backdrop of various anatomical drawings of the liver and pancreas. 
