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: 30–40% 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-team’s 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: 0.585–17.891; P ¼ 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. 
