Debashish Bose, MD, PhD, FACS, Associate Director of Surgical Oncology, Director, Center for Hepatobiliary Disease, The Institute for Cancer Care at Mercy, Baltimore, talks about how surgeons are evaluating a high-tech tool to increase patients’ odds of survival from pancreatic cancer.
Tell me a little bit about the NanoKnife. Can you describe what it looks like and how it works?
BOSE: The NanoKnife is essentially a way of delivering an electric shock to tissues. This is actually old technology in terms of how long we’ve known about the effect of an electric field on cells. In the past, we tried to get DNA into cells to test what genes do. One of the ways of doing that was to create pores in the cell membrane and then have the DNA get in that way and then close up. We call that reversible electroporation. If you subject the cells to a little stronger field, that pore formation becomes irreversible, which the cell doesn’t like and therefore commits suicide after that. So live cells are affected by this technique. The electricity delivered is not enough to cause tissue damage by heat. So, we think of ways of ablating tissue and one of those ways is to create a burn, essentially. If you give enough electricity, you can cause a burn, right? But if you give just enough, not too much, you’ll cause live cells to form these pores, but the structures around them don’t get destroyed. So, this is one of the keys to understanding why we use NanoKnife. We use it as a local therapy to treat areas which we don’t otherwise want to damage. Other things like blood vessels or bile ducts. One can almost think of it like delivering radiation therapy. It’s a very similar kind of mechanism in terms of what the cells do and not damaging the surrounding tissues.
So, there’s no cutting?
BOSE: Well, no. Everybody should understand that I’m a surgeon so the way I do this is cut you open and put those needles in to create the electric field. Now, it can be done through a percutaneous method. There are people who do it with CT guidance. So, they do a CAT scan and place the needles through the skin and other structures to get to the target tissue. But from a surgical point of view, this is done as an open surgery. So, it is invasive in that sense.
But you’re not actually cutting at the tumor or the cells to excite them?
BOSE: It gets more subtle than that. What we’re talking about is why do we do it? We do it in a couple of different circumstances, one of which is what we call locally advanced pancreatic cancer. That’s a pancreas cancer that by sort of conventional standards we would not be able to remove. With NanoKnife, after doing chemotherapy and radiation to that tumor, we assess whether we can do surgery with NanoKnife. It can take essentially the form of we get in there and all we do is treat it with the NanoKnife and don’t cut anything out, or it can take the form of us cutting out what we can and treating what we’re leaving behind with the NanoKnife. The data so far demonstrates that people with locally advanced pancreatic cancer, whether we treat it with a NanoKnife only or treat and resect some, do better than if we had done nothing at all.
What’s the benefit when you’re talking about these locally advanced cancers?
BOSE: Time. Survival times are better. Right? Have we proven that in a trial? No. The trials are ongoing. But in selected patients, we do feel that using the NanoKnife gives them more time than not doing anything at all. It’s at least on average a good six to eight months compared to historical controls. So, folks with locally advanced pancreatic cancer who get chemotherapy and radiation might live anywhere from 16 to 18 months. The average patient who gets treated with NanoKnife on average gets about 24 months. I have patients who I’ve treated as far back as 2016 who are alive today without evidence of disease. So, for some patients it’s something that does make a difference and it’s something that can help people live longer.
What does that extra time represent for patients?
BOSE: For an individual patient, it’s very hard to predict. Sometimes that means the difference between seeing a grandchild graduate from high school or college. It might mean the difference between seeing a child married or having a baby. It’s just looking for a little extra time. That’s our most precious commodity.
You mentioned the NanoKnife technology has been around for a while. Has it been used in treatment for other types of cancer and only more recently with pancreatic and liver?
BOSE: Yes. I particularly use it for pancreas and liver disease. In the liver you can have cancers that arise primarily in the liver, like hepatocellular carcinoma, but often you have cancer that has spread to the liver. Typically, it would be for something like colon cancer. It spreads to the liver. In patients with colon cancer who have metastatic disease in the liver, everything is about location, location, location. Our ability to remove those tumors has everything to do with where they are and how much disease there is. So, in some patients it may mean that we must take too much liver out to fully remove all the disease. In those patients we’re looking for ways of treating the disease that we’re not going to take out to preserve some liver so that the patient can stay alive. How do we do that? We do that through a variety of methods. The NanoKnife provides us a way of treating tissue that is around sensitive structures where we don’t want to have a burn. Let’s say a tumor is next to a blood vessel that’s important for the liver to survive. We can still treat that tumor with NanoKnife without creating a burn and damaging the tissues around it. So, we use it a fair amount in the liver. NanoKnife has been used in other tissues, as well. It has been looked at for prostate cancer, and that’s still an experimental kind of thing, but it is something that people are looking at. In Europe, there have been some small trials on breast cancers where if you can ablate without causing heat damage, it might make some sense to pursue something like this. It’s still an evolving technology in terms of the contexts in which it is used, but certainly one of the reasons to target pancreatic cancer is because pancreas cancer has always had this glaring problem, which is once it’s too close to these blood vessels there’s not much you can do about it.
Precision is everything in surgery, but you don’t have a whole lot of room to work because of the blood vessels that are close by. Is that the biggest benefit for you, that ability to precisely treat the areas?
BOSE: The benefit is that where I’m worried about leaving disease behind at a microscopic level, whether I can see it or not in the operating room, I can do something about that area, or margins, that I’m worried about.
Can you tell me a little bit about Barbara?
BOSE: When you meet Barbara, you’ll find that she’s a very positive and happy person. She came to us with kind of out of the blue onset of jaundice, which was reflective of her bile duct becoming obstructed by cancer. She came into the hospital, and we got that fixed by placing a tube in the bile duct to stent the area. We looked at her CAT scans and she had a tumor that was encroaching on some critical blood vessels that we couldn’t otherwise remove. She was not looking like someone we could easily do surgery on. But we thankfully have a multidisciplinary team here that functions very well and started her off on chemotherapy in which she had a very good response. In her case, because she had such a great response to chemotherapy, we decided that surgery might be the way to go instead of doing the radiation first. So, we did surgery on her along with NanoKnife along the blood vessels to treat that area that I was worried about. It turns out that once we took it out, her margins were negative, but very close. Her lymph nodes, which is the other kind of indicator of how someone will do, those were also negative. What we could tell under the microscope was that a lot of the cancer had been killed by the chemotherapy. But because we don’t trust pancreas cancer, we followed that up with radiation therapy and she has done extremely well. She turns out to be one of those people who because imaging is imperfect, we don’t know how they’re going to respond to treatment. You hope and pray for all these things to come together the right way, and for her it definitely did. Her disease was not as bad as her imaging suggested, but on top of that she had a great response to chemotherapy. So now we would consider her to be in one of the more favorable categories in terms of her statistical chance of surviving. On average, a patient like her should get at least three years before we see potentially any further progression of disease and that progression could either be locally recurring or in the liver, which would be sort of metastatic disease.
What stage was she when she was diagnosed?
BOSE: Well, she would have been considered stage 3 based on the clinical impression, which would include the imaging and her laboratory studies. But in the end once we did her surgery, she really was only stage 2.
Is there anything I didn’t ask that you would want our viewers to know?
BOSE: I think that one of the important things to understand about cancers in general, especially in the GI tract, is that it’s important to get evaluated by a multidisciplinary team that can consider all options. We’re not just looking at surgery or chemotherapy or radiation. We’re trying to figure out what’s the sequence. How do we get to a surgery if we can’t do the surgery now? Should the person have surgery first? Should they have it after chemotherapy? Now, in cancer care that has become the standard and best way to do it, but that’s not available everywhere still. So, it’s important to get evaluated by a multidisciplinary team who knows what they’re doing with these kinds of cancers.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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