Constantinos Hadjipanayis, MD, PhD professor of neurosurgery and oncological sciences and a site chair for our Mt. Sinai Health System Union Square campus, talks about a new device for measuring brain tumors.
I want to talk to you a little bit about a device that helps doctors with what I guess you called a virtual biopsy. Can you explain, first of all, what the device is and what it’s intended to do?
HADJIPANAYIS: The device that we’re using is a handheld probe that we actually use during surgery as part of a clinical trial. So, we’re actually collecting data in our patients who consent to be part of this study where we’re using the probe to collect data from tissues during surgery. We really want to understand the composition signature that we can collect from tumor tissue and the surrounding brain tissue. The concept is that, if we can detect the tissue better, then we can really focus on resecting just the tissue and sparing the surrounding functional brain in patients.
How does the device go about assessing what needs to be sampled and what might be able to be left alone?
HADJIPANAYIS: The device works on a concept that actually was awarded the Nobel Prize in 1930 to Dr. Rahman. He was an Indian physicist who basically described how light, when it touches objects, scatters, and the way light scatters can provide a signature to that type of tissue or molecule or what have you. And you can also detect the vibrational patterns of tissue, and that allows you to differentiate, possibly, a tumor cell from a normal cell. And believe it or not, that concept has survived the test of time and now, almost 100 years later, we’re using this technology in human patients to gather data so that we can develop a library of signals from the device that uses the laser light that scatters on tissues so we can understand what that tissue represents.
How many patients and what kind of findings have you had from the trial?
HADJIPANAYIS: It’s all preliminary now. We’ve done four patients. We have our fifth one on Friday. And we’ve done a variety of tumors. We’re really kind of sampling multiple portions of the tumor during surgery. So, the device is a handheld device that allows me to basically use it as a pen. And I touch the tissue that emits the laser light, and then a signal is obtained from the probe. And then we collect that data. Now, in tandem to the signal, we’re actually taking little biopsies of tissue samples so we can correlate that Rahman spectroscopy signal from the probe where I’m stimulating on the tumor tissue. And that tumor tissue then is examined by the pathologist and the neuropathologist who then tells me, you know, this is tumor, this is not tumor. Here you have so many tumor cells. So, the idea is that we quantify this Rahman spectroscopy signal to tumor cells and the number of tumor cells so we can now understand, you know, both quantity and what type of cell it is?
Just to clarify for our viewers, you’re not excising anything, are you? You’re just touching certain area?
HADJIPANAYIS: Yeah, this probe, it’s just the size of a pen and it has a fiber optic cable that attaches into a computer tower. I just touch it on to the tissue that I want to measure the Rahman signal from. But I do take a little piece of that tissue, a little one to two millimeter piece of that as a biopsy. And the tissue that we take is tumor tissue, so we want to take that tissue out. And the tissue that we look at surrounding the tumor tissue is an area that, you know, is also kind of infiltrated by cancer cells in many instances, especially with the cancer we know as glioblastoma, which is one of the most challenging tumors for us to take care of as neurosurgeons.
Is this only being tested in the glioblastoma, in the brain tumors or does it have ramifications for other kinds of tumors?
HADJIPANAYIS: It actually has applications for any brain tumor, and the clinical trial we have open is for 50 patients total for any brain tumor. We’re particularly interested in the glioblastoma population because of the little fingers the tumors grow into the brain to see if we can detect those fingers, because they’re invisible to our naked eye. And, you know, as we do our surgeries, we try to use as many technologies as we can to help us see the cancer cells and tissue to remove it more safely.
How do you and your colleagues access the tumor? Is it an open surgery? And then accessing the tumor, if you could explain to our viewers how you access it.
HADJIPANAYIS: In many instances we perform what’s called a craniotomy, it’s a temporary removal of the skull, and that allows me access to the brain. Then I use what we call neuro-navigation, it’s almost like a GPS technology that allows me to find exactly where the tumor is under the surface of the brain with a wand, a little probe device, and that guides me to where the tumor is. Then we have all sorts of technologies available to us, especially here at Mount Sinai, where we combine the use of a robotic-assisted digital exoscope that allows me to kind of visualize the tumor, very well and magnify it, delineate it. Then in some patients, we actually have them drink an agent called 5-Aminolevulinic acid, 5-ALA, and that allows the tumor to light up during surgery.
Is it a fluorescence?
HADJIPANAYIS: That’s a fluorescence marker. That’s something that we helped bring to FDA approval in 2017, and now it’s being used in almost half of all, from what I understand, glioblastoma surgeries around the country.
I know we touched on it a little bit, but what’s the benefit, doctor, for you and your colleagues to be able to have this more precise tool?
HADJIPANAYIS: Well, the benefit is how can we more safely resect tumors in a way that we can get as much of the cancer cells as possibly without impacting the surrounding brain? That’s where there’s a delicate balance. We want to, as neurosurgeons and oncologists, take away as much of that tumor as possible. In the brain we have to worry about the surrounding tissue and being able to detect it and delineate it better becomes much easier for us when we have to go and take this out because we do know that outcomes are better with almost all cancers when we can more completely remove the tumor, and the same thing applies with brain tumors on the whole.
This tool is just for biopsy, just for taking that little sample? Or does it have further uses?
HADJIPANAYIS: We believe that, based on this data and we still have to analyze it. Again, it’s a clinical trial, so we’re still in the middle of it. But we believe this tool will allow us to kind of push the boundary of our surgery because we’ll have more information, we’ll feel more confident understanding where the cancer cells reside and where they don’t. And then, you know, kind of push our surgery to that edge. It’s all about how far we can go out in the resection margin and get the tumor, and that’s where these technologies have just been really important in advancing our field.
You had mentioned that it’s good for any brain tumor, but especially important for glioblastoma. Again, for our viewers, is glioblastoma a very difficult cancer to treat? Can you give me just a little context?
HADJIPANAYIS: It really is. It’s such a terrible cancer. All of us are impacted by glioblastoma. We have family members, we have friends, coworkers. I mean, you hear about it in the news almost all the time now, and we have made such small progress in that form of cancer in terms of surgery, radiation, chemotherapy. These cancer cells just are really resistant to all our therapies. So, we know that, if we can get to them and resect them better, the outcomes of our patients could be better overall. So, you know, this is a multi-combination approach where we can look at different technologies to really attack it. There’s not going to be one silver bullet for glioblastoma. It really requires a number of different things that we can get to it from different angles.
You had mentioned it’s in clinical trial, is it phase one or is it different with devices?
HADJIPANAYIS: Well, it is a little bit different. So, a phase one would look at concentration differences. So, this is really kind of just collecting the data. It’s not a therapeutic aid technology. So, we’re not using this to guide our surgery, we’re just using this to collect information right now and we plan on using artificial intelligence to compile all this data so we can determine signal versus signal equates with this type of tumor. We’ll have a library of signals that correlate with tumor types, tumor cell number, and I think that’s what we’re going to be using moving forward. This builds on a lot of important work that was originated out of McGill in Canada, in Montreal. So, you know, they’ve really started this work and I am really honored to be part of this clinical trial as the first in the United States to be able to carry forward this research.
After the 50 are enrolled, what would the next step be?
HADJIPANAYIS: So, once we look at that data and use artificial intelligence to look at our data as well as data that was collected from McGill University, we’re going to then hopefully, take this to the next level. It may be, at some point, used in a commercial way in patients, again, as a handheld device that will help us guide surgery. It’s all about decisions we make as neurosurgeons, but our decisions during surgery are based on the information we collect and the technology and tools that we use.
How does it work?
HADJIPANAYIS: It’s as simple as probably the length of a pen and the tip of a pen. You can see there’s a fiber optic cable. This connects into a computer tower and that allows us to collect the light scattering data from the tissue. So, I place this on the tissue, the tumor, and then there’s a laser emitted from the tip of this and then that data is collected back. It takes literally two seconds and then that data gets collected back so we can look at all the composition of the tissue that we looked at.
When you use the fluorescence with it, you’ll be looking at images that potentially light up as well?
HADJIPANAYIS: So, the nice thing about the fluorescence is that’s showing me the tumor. In addition to using a robotic exoscope to show me the tumor, the fluorescence allows me to localize where the tumor is, and then I can use the handheld spectroscopy device to really focus on those fluorescent regions of the tumor.
There’s a camera in there?
HADJIPANAYIS: Well, it’s actually a laser device. So, it emits a laser, the laser bounces off the tissue that it’s on, and then that data’s collected, which is the spectroscopic data, into this fiber optic connection that goes right into the computer.
Is there anything, doctor, that I didn’t ask you that you would want people to know?
HADJIPANAYIS: Well, I think with any technology, we have to understand its role and that’s where it’s important, in clinical trials, to really flesh out some of the nuances with the technology. As you can imagine, while the principle is 100 years old, bringing it into the clinic there’s a big jump and we have to understand, some of the data that we’re dealing with and we have to understand how sensitive it is. I’m a firm believer that this Rahman spectroscopy imaging in the OR is going to be something that we’re going to incorporate moving on. There’s been some other efforts that have been quite promising looking at this type of spectroscopic imaging for using as pathology in the OR where we take tumor tissues out and then look at it in the back table with this device to allow us to visualize the tissue. So, it’s a technology that’s here to stay and it’s going to have its role and we’re trying to define it for actual surgery.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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