Irreversible Electroporation (Nanoknife). Thought: Combining Nanoknife with Coley's Toxins?

For almost two years, I've been keeping track of an ablation technology that offers significant advantages over traditional ablation techniques. Those of you who have prostate, liver, lung, kidney, lymph node, bone or pancreatic cancer should definitely invest time into studying this. I'm sure it has its limitations, but you need to pay attention because the articles and papers seem to indicate it may be an additional option in cases where surgery or RFA/Cryo may not be suitable.

"IRE technology allows for extreme precision. While targeted soft-tissue cells are killed, blood vessels and other important structures in the area remain functional. The body is able to naturally rid itself of the dead cells. In regenerating organs, such as the liver, the dead cells are replaced with healthy cells".

It's very similar to Radio Frequency Ablation (RFA). However, conceptually, this tumor ablation technology offers very important intrinsic advantages that are especially important when one is looking for a tumor-debulking procedure that's more compatible with immunotherapy.

Standard RFA (radio frequency ablation) generally kills everything in the kill-zone, including blood vessels and nerves. IRE supposedly does not damage blood vessels and nerves. This is a KEY advantage.

With intact blood vessels, your immune system can come and "clear out" dead cancer cells. This means much faster healing. In addition, it may also promote training of the immune system to recognize tumors (this is my own hypothesis). Furthermore, preservation of nerves is an obvious advantage - less pain, and preserved function.

Nanoknife website

Here's the main website for Nanoknife: http://www.angiodynamics.com/products/nanoknife . On the right column, you'll see many scientific documents as well as the user manual.

In addition, here are some relevant news articles:

1. New NanoKnife® Procedure Treats Pancreatic and Liver Cancers with Electric Fields at Cellular Level
   Dr. Watkins used IRE to treat a typically fast growing and fatal tumor, pancreatic cancer. This marked both the first use of IRE at SBUMC and the first-ever use of the technique on a pancreatic tumor. Another pancreatic cancer patient is scheduled for the procedure during March 2010. “Our first IRE patient had her six-week follow-up PET scan in early February, and the initial report showed no activity, making her a radiographic complete response at this point,” Dr. Watkins said. “Hopefully, she’ll have a durable response, which only time will tell, but from a local disease standpoint, the technology did just what we had hoped.”
2. NanoKnife giving patients hope Treatment's aim to kill cancer cells using electrical impulses
   "The system is minimally invasive and has been used to treat prostate, liver, lung, kidney, lymph node, bone and pancreatic cancers. Someone with multiple lesions in different organs wouldn't be a candidate, Hays said." (note: combined with active immunotherapy, I would still contend it may be worthwhile for reduction of tumor load in a patient with metastatic disease)
   
3. Doctors tout NanoKnife for easy tumor removal
   "A University of Miami doctor recently removed two cancerous tumors from a patient's liver using only three needle-like probes, a computer and a powerful burst of electricity.... The patient, Maria Gomez of Delray Beach, went home the next day with little pain and no bleeding. She has a good chance of avoiding the liver transplant that was being considered before the operation in early January, says Dr. Govindarajan Narayanan, chief of vascular interventional radiology at the UM Miller School of Medicine."
4. BAPTIST HEALTH Debuts NanoKnife Treatment for Lung Cancer (Jan 05, 2010)
   "IRE is a remarkable new minimally-invasive cancer treatment that kills tumors in a completely new way," said David Hays, MD, Section Chief, Interventional Radiology Department at BAPTIST HEALTH. "The tumor cells are killed but the surrounding framework of the organ is left intact. IRE expands our options for Interventional Oncology treatments and further enables our collaboration with medical professionals to provide the best possible treatment for our patients with cancer."

Additional links:

1) Nanoknife was "invented", by this electrical engineering professor from Univ. of Berkeley: http://me.berkeley.edu/announcements/rubinsky_nanoknife.htm

2) He has research papers on his university website here: http://www.cs.huji.ac.il/~rubinsky/electroporation.htm

3) Clinical trial: http://clinicaltrials.gov/ct2/show/NCT01078415

This clinical trial is for liver cancer and is in Italy

Pros and cons

The minimal invasiveness and superior healing profile offered by IRE will help minimize the following side effects:

• Postoperative pain
• Ablation “shock” syndrome
• Ischaemic necrosis
• Cavity formation
• Fever
• Long stay in hospital
• Prolonged recuperation after
• Drains
• Wounds
• Infection

The possible limitations of IRE are:

• Cardiac arrhythmia without synchronization (this should be avoidable)
• Electrode track tumour “seeding” (no worse from RFA or Cryoablation)
• Possibility of pancreatic duct leakage
• Electrical effect on brain (this may be a limiting factor for brain tumors)
• Unsuitable for tumors larger than 5cm

Combining Nanoknife with Coley's Toxins?

OK, I'm no oncologist and I'm the first to admit that my understanding is extremely limited. However, for a long time, I've been wondering about something for a long time:-

When a surgeon or interventional radiologist tells you that your cancer is inoperable, what does that really mean? Is it inoperable because it's metastatic, and that operating on one tumor would be "useless" because the others will kill you anyway? Or is it inoperable because attempting to extract that specific tumor would result in some life-threatening complication?

That brings me to IRE's size limitation. I've seen here and there that IRE has a size limitation of tumors < 5cm or so. Some places say 4, others, 6. But the idea is there's a size limitation in that vicinity. Now, why can't repeat applications be done? Again, is it because ablation portions of a tumor at a time would result in a life threatening complication? Or is it because they're afraid of the increased risk of tumor seeding with repeat needle insertions?

If tumor seeding is the concern, then would it still apply to a cancer patient who's given no other options and left to die? What about combining repeat IRE ablations with active immunotherapy such as Coley's Toxins? The hope would be that active treatment with Coley's Toxins would wipe out any microscopic tumor along the needle tracts. One could pre-treat the patient with Coley's, then ablate some of the bulkier tumors with IRE, then go back to Coley's. The fast healing and minimal complications intrinsic to IRE would allow as short a gap as possible in between Coley's.

Again, my knowledge of surgical and ablation complications is extremely limited. I need to understand this better. When I learn more, I'll update this document. I'll try to get on this ASAP.