Safety of irreversible electroporation treatment
for metastatic disease in humans
Silk Mikhail; Wimmer, Thomas; Getrajdman, George; Durack,
Jeremy; Sofocleous, Constantinos T.; Solomon, Stephen B.
Interventional Radiology & Image Guided Therapies
Memorial Sloan Kettering Cancer Center. New York, NY
Email:sofoclec@mskcc.org
Agenda
• Background on Ablation Devices
• Physics (RFA, MWA, IRE)
• Pre-Clinical Data
• Clinical Applications
Thermal ablation uses Electromagnetic Spectrum
MWA
300GHZ
300 MHz
R
F
A
3HZ
Thermal ablation uses the EM frequencies of 3 Hz and 300 GHz.
Irreversible Electroporation
• Electroporation
– Electric pulses create
tiny holes in the cell
– Temporary as long as
the energy is low
• 360 V/cm
– Chemotherapy and
Genetic therapy
delivery
• “Irreversible”
– Higher energy
• 680 V/cm1
• Create permanent
holes in the cell
• Cell loses essential
molecules and internal
signals tell the cell to
die
Electroporation
• Reversible electroporation is used to
allow genes and drugs to enter cells
(300-600 V/cm)
• Direct current pulse leads to
elevation of transmembrane
potentials creating permanent cell
membrane pores: ~1,500 V/cm
• Strong electric fields
applied across a cell can
cause:
Irreversible permeabilization
of the cell membrane: “IRE”
How IRE kills cells
Advantages of IRE
• IRE is non-thermal
– Little to no scar tissue formation
– Structural Protein Sparing
• Nerves and bile ducts in the area of ablation have the
potential to heal after treatment
– No heat sink effect
• Compared to thermal techniques where blood flow dissipates
heat. Electric pulses are not effected by blow flow.
Patient Demographics
Table 2. Tumor characteristics
Variable
Data
Total Tumors
43
Table 1. Patient Demographics
Tumor Size
<1 cm
6
Variable
1-2 cm
13
2.1-3 cm
12
>3 cm
12
Total number of
patients included
Age range:
Data
29
42y-81y
Tumor location
Liver
29
Soft Tissue
12
Lung
Sex:
2.3cm
1
Tumor type (%)
Male
16
Female
13
Treated tumor lesions
43
Metastatic Colorectal
26
Metastatic Pancreatic
6
Metastatic Endometrial
3
Metastatic Prostatic
3
Metastatic Leiomyosarcoma
2
Metastatic Hemangiopericytoma
1
Metastatic Ovarian
1
Metastatic Thyroid
1
Multiple IRE electrodes to treat larger
lesions minimum:
2 parallel electrodes spaced 1.5-2 cm
NO Heat Sink Effect
Case close to bile duct and major vein
• Pre-Tx
• Tx
• Post-Tx
• 3 mo. f/u MRI
No tumor for +778 days
Perivascular/periductal Liver Metastases
28 patients/ 65 tumors: 1 arrhythmia; 1 PV thrombosis (3%)
6 months: 92% Complete Ablation
Kingham P et al: IRE for Perivascular Hepatic Malignant Tumors. J Am Coll Surg 2012; 215(3): 379-87
Animal
Lungto
IREbronchus
LUNG
close
Post IRE: GGO
Applicators
1 week
3 weeks
Tumor near airway
• Pre-Tx
• Tx
• Post-Tx
• 3 mo. PET scan
IRE as an Ablation Tool: Potential Advantages
• Non-Thermal:
-Application in Locations non eligible for Thermal Ablation
-Limit recurrences near vessels by avoiding the “heat sink”
effect
• Cellular Kill Mechanism Avoids Damage to:
- Extracellular Matrix. This may result in fewer complications:
Near Bile Ducts, Intestines, Ureters, Bronchi, Vital structures.
51 year old with rectal cancer recurrence near
rectum
NO tumor for +565 days
IRE Rectal Wall
Transmural Necrosis; No Perforation at 14 days
Applications: IRE
Where Thermal ablation is NOT feasible
• Pancreas: Locally advanced adenocarcinoma 100% success
at 90 days. Martin RC e al J Am Coll Surg 2012; 215(3): 361-9
• Perivascular Liver Tumors. Kingham P et al: IRE for Perivascular Hepatic Malignant Tumors. J Am
Coll Surg 2012; 215(3): 379-87
• Prostate: A potential Therapeutic Paradigm Shift. Ward JF Curr Opin Urol
2012; (2): 104-108
• Intracranial: Canine brain Surgery. Garcia PA Conf Proc IEEE Eng Med Biol Soc 2009:
6513-6. and Technol Cancer Res Treat 2011; 10(1): 73-83
• Blood Brain barrier Disruption: Rat Hjoui M et al. MRI study on reversible and irreversible
electroporation induced blood brain barrier disruption. Plos One. 2012;7(8)
• Small Intenstine: Rat: Complete ablation but recovery of
Epithelium in 3 weeks. Phillips MA. Br J Cancer 2012; 31; 106(3): 490-5
Enhancing Irreversible Electroporation
A zone of Reversible
electroporation Surrounds the
Area of IRE
A lethal agent can be targeted
to the reversible zone:
Reversible
Irreversible
Electrochemotherapy
Gene Electrotransfer
Electrochemotherapy : A new technological approach in
treatment of Liver Metastases. Edhemovic et al Technol
Cancer Res Treat 2011 Oct; 10(5):475-85
Treatment Planning of Electroporation-Based medical
Interventions: electrochemotherapy, gene electrotransfer and
IRE Phys Med Biol 2012; 7;57(17)5425-40
Model assumes 360 V/cm
threshold for reversible and 680
V/cm threshold for irreversible
Conclusion
• Unlike Thermal Ablation, IRE, can be performed
in close proximity to bile ducts, major vessels,
bladder, rectum, and nerves, with an acceptable
safety profile.
• Longer term follow up is performed to determine
efficacy.
• Further research will determine the potential of
this new ablation technology
sofoclec@mskcc.org