Penn Medicine’s John Y.K. Lee, MD, MSCE, discusses TumorGlow™ Second Window ICG in Brain Tumors at the Precision Surgery Intraoperative Molecular Imaging 2022 conference.
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So it's my pleasure to introduce the last speaker for this session. Dr john lee. So dr lee is a professor of neurosurgery and head and neck surgery. He's the medical director of the gamma knife center and the clinical clinical director of the Center for Precision Surgery here at the School of Medicine at the University of Pennsylvania. Dr lee is prevent presenting tumor glow Second window I. C. G. And brain tumors uh join me and welcome welcoming dr lee. So I knew we'd fall behind so I'm gonna move fairly quickly. But one thing I want to say that uh presenting on I. C. G. It sounds boring but because I see he's been around a long time it's not targeted. It doesn't have any activate herbal component to it. But I think it's very important to recognize is that the E. P. R. Effect or what we keep calling the pR effect. This passive delivery probably represents some part of how these drugs are getting to the tumor. And what component of any particular diet is is can be attributed to I. C. G. Is very hard to tell obviously. But I think the fact that we can just give a bolus dose of I. C. G. Wait a few hours or in our case in this in this presentation 24 hours and then still find lots of I. C. G. And near and in the tumor implies that there is an there's clearly some mechanisms going on that have nothing to do with what we believe is important. And I look forward to some future talk hoping to elucidate what might be going on. So the PPR effect what we're doing with second window I. C. G. And I apologize to Tolia for confusing the literature when we came up with that name. And we and we started using that term but I think this is still a very valuable technique so we'll move quickly. Um um I'll move so quickly that you didn't even see the slides. Okay. Um G. B. M. We talked we've heard a lot about it. I've heard a lot about five L. A. So we're gonna move quickly. Um I think this is interesting because when we do M. R. I. Scans we give this contrast agent that just leaks into the tumor and then we get the imaging, it changes this T. One relaxation and we get the M. R. I. And you have this beautiful view view. This is essentially what I believe I am seeing with I. C. G. And our technique. And so pretty much any contrast enhancing tumor and brain at this point. I believe we can visualize with this technique with a cheap boring die. The other interesting thing is um and I'm very fortunate is that the brain has this thing called this blood brain barrier and it is remarkable because I have no background Alex Chanin came up here and talked a little bit about background and one of the reasons why we have to wait so long for some of these guys. And actually you just showed her slides with this with the peptide um F. G 001, the UK you party, how there's too much background still circulating and um the brain can potentially have very little background. And so I'm taking advantage of that with my technique, our technique. So so here's an example. Here's the brain. Now. I just did a. K. Two cases with my junior resident one with I. C. G. And one without I. C. G. And in both cases the only reason it was without I. C. G. Was simply because for some reason my camera wasn't working. Uh it just kept rebooting it and I couldn't get the images. So what struck it was great to hear a P. DY three resident junior residents say this. She said we did one case with it and it looks just like this. You you don't know where to make your core tasek to me like where is this tumor? It's a sub centimeter tumor or this was a G. B. M. This occipital one. But the other two more we could talk about was a met um it's under the brain. All you see is normal brain like where do you decide to dive in? You know you take your divining rod. So this divining rod looking for water in our case is this navigation probe. So this uh and um where do you make your cut your initial cut to go in because all of this presumably is working this brain because it looks normal. Um So the nice thing with our technique is because it's near infrared we can just clearly decide to make the cut to the shortest path to the tumor. But we did a case without it. And she I let her make the decision where to make the cut. She makes the cut she looks and then she spends a long time looking for the tumor. And I'm letting her struggle just because I wanted to prove to her the value of our of of our imaging techniques. And um it took a while she couldn't find it. So then I came in and use kind of old fashioned techniques. Found the tumor. And then afterwards she says wow every other surgeon just has to cut and just hope they find the tumor. Whereas you with your with the die, you don't have to do that. And so it was it really helped prove to me the value of what we're doing today and the value of just using simple old I. C. G. So again near infrared dye you can see through the normal brain normal cortex pseudo color overlay. You can um prove we I don't need to. This is a fairly sophisticated audience. So I'll go through some of this. Um I credit steve cho who did a lot of our early work. This is another topic that I think gets needs a little bit of discussion because it came up in multiple other talks um specifically what happens in the areas of necrosis. Um So in this study um steve just compared five A. L. A. Which requires that enzymatic conversion to support for nine and accumulation. So we have Puerto port for nine only on the periphery of the tumor. It was interesting. One of the ph sensitive uncle nano's di there was a question about why is there only die on the periphery? And then this also came up in one of the other talk. The first talk this was eric Henderson's talk where with the abbey his alfa body E. G. Fr die. He was only getting peripheral contrast or peripheral dye accumulation. So he supplemented it with our second window I. C. G. In order to get I. C. G. Into that necrotic center core. And for some reason and I don't think it's well understood. We have plenty of I. C. G. In that central necrotic core and I see this all the time. So if the patient had radiation necrosis for example the I. C. G. Will be stuck in that necrotic area or if their tumor has central necrosis because it's outstrip supply growing too fast and then we'll also see plenty of I. C. G. In that central area. So I don't know what the answer is. There was actually also a question that I should probably address um that came in through the chat online asking this exact same question and um dr rice also address that question. So I can go through that a little bit later. Um So it's an interesting phenomenon but we certainly see lots of. I said for my work I chose the camera and I again credit Brian Pogue. But Alicia de Souza for this paper. So we chose the camera with the highest sensitivity, the greatest dynamic range. Use multiple different um I'm gonna speed through a lot of this. Um we we did uh a lot of cases 370 patients and many different histology which I'll summarize here. Um We did have some adverse effects only in the beginning when we're infusing a little bit too fast. And this is all either five mics per kilo or 2.5 mics per kilo. And uh so for G. B. M. Uh So this is the example I showed earlier. So I do that. I did the reception just with white light only and then looked at the margins and only biopsied. So at the peripheries of the biopsy, then we would look for additional um tumor biopsy and send that and calculate R. P. P. B. S. And M. P. V. S. Um so this is an interesting case. It's a 21 year old female new onset seizure. So because this is right frontal lobe I can do a surgery that looks more like what sunil would do or what my colleagues in oncology really would do which is a much larger resection of the entire frontal lobe. And um so there's that piece of her frontal lobe. And what was remarkable to me is there's like two pieces of I. C. G. Stuck in that front. And or our contract gadolinium on that M. R. I. And you can see it clearly when you just look with the I. C. G. And then in the near infrared. So to me this is a really good evidence that we are imaging very similar things with Natalie linney. Um And I. C. G. The other interesting thing is then 15 years, five years later, six years later we went back to the paraffin embedded blocks. We pulled those out and then we looked for I. C. G. And it was remarkable that it survived fixation and storage and it's still available. And actually one of our presenters will um has looked at that and he'll be talking later today. So um with this technique we have excellent sp Rs five hour. We can see through the door. I can see through the brain and our sensitivity can be very high. But our specificity is not so great. Only in the 50% also are negative predictive value. Also is not as high as our PPV. So um is interesting. Um The real clinical question though is how does it change surgical decision making? And that's the subject of future trials. So we we've we've published this, we published that this is actually more accurate than our navigation because navigation gets becomes inaccurate. Over over time we have correlated the residual fluorescence with a post operative. MRI's showing again that the residual gadolinium enhancement which we use as a proxy for GTR. Or definition of gross total resection can be predicted by just looking at your post, looking at your margin with the near infrared camera. So um uh So I was just comparing it to five A. L. A. But let's move, we'll just skip through some of this. Um We can use it for brain maths or anything. Again, anything that's contrast enhancing. And so um we have done this as well. And this is also very successful. Again, excellent melon melanomas are challenging. If there I I don't I can't always detect a melanoma with this second window. I see g technique. Um But again, our sensitivities and specificities are pretty but specificity for METs are low. I can find if I see a uh something at the end of resection, it's not necessarily um tumor. So our PPV drops because the prevalence of tumor in a MET in the surrounding tissue is lower. So this is just an example of that. And in the sake of time, I'm just gonna we've used it in multiple other intracranial tumors? I think it has a lot of value in certain types of benign tumors because when you do a benign tumor, your surgical in many of these tumors, surgical resection obviously matters. So it makes a huge difference in recovery. I have a patient I did seven years earlier with a cranial ngoma, endoscopic through the nose, tiny tight, a little residual on the hypothalamic wall. Um, so I I think for the sake of time, I'm going to move forward. But I want to thank my students. I want to thank everybody for coming here today. And there's a lot of things that we can discuss. So let's take some questions.
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