A Mathematical Model of Perineural Tumor Spread, Pilot Study on Two Cases, Dr. Capek. So first, thank you so much for being here so late. And thank you so much for the opportunity to show you a few slides on this small, fun project combining mathematics and perineural spread we did with Dr. Spinner. I'm Stefan Capek. I'm a second-year resident at UVA. So a few years back, we introduced this concept of neoplastic lumbosacral plexopathy caused by perineural spread when the tumor cells spread from the primary side, where it's prostate, bladder, rectal cancer, along the autonomic nerves to the lumbosacral plexus, and then within the plexus proximally, all the way intradurally, or even to the other side. And of course, distally to the sciatic nerve and other branching nerves. And this form of plexopathy is quite unique to other forms of nerve injury. First, it's a very slow process. It takes years to develop. It's hard to diagnose it unless you know what to look for. And even if you know what you're dealing with, it's hard to treat it. You can't resect the plexus. So you have this new clinical entity, which we are going to be seeing more and more of. First, because we know what to look for, and we have better imaging tools. You know, 3T MRI is probably the standard of peripheral nerve immobilization right now, but we have 7T MRIs coming up, PET MRIs, et cetera. And also, better local control of the primary tumor gives such a slow process, as perineal spread, time to develop. So you have this new clinical entity, but we really don't have any data on initial history. How does this patient do? And to overcome this deficit, we try to come up with a model to model and sort of predict how the tumor progresses down the road. So what did we do? We reviewed our series of perineal spread in pelvic tumor, and we selected patients with sequential or multiple pretreatment MRIs. We segmented or picked contrast-enhancing portions of the plexus, we aligned them up, and we calculated the tumor progression rate. Once we had that, we modeled it on an ATLAS image obtained from a healthy subject. We had only two subjects in a series, and subject one was a 7-year-old male with a history, remote history of prostate cancer, who comes back 15 years later with left low extremity weakness, numbness, and pain. And the MRIs in the top row, they showed the progression of the tumor, first from infiltrated sciatic nerve and S1 nerve, all the way into adrenal and even to the other side. And the images in the lower row, they show the progression of the enhancing part of progression of the tumor within the plexus, and then even in the contralateral plexus. Once we had that, we calculated the tumor progression rate, which was about 5 millimeters per month, and we modeled it on an ATLAS obtained from a healthy volunteer. Importantly, when you compare the simulation to the actual MRIs, it correlated pretty nicely. And it was subject number one, and we did exactly the same thing with subject number two, who was a 50-year-old female with a history of cervical cancer, which spread to the left lumbosacral plexus. It was a little bit more aggressive tumor. It was about twice as fast, as you can see on the simulation as well. And again, when we compared the simulation to the actual MRIs at given time points, it correlated pretty nicely. So I know it's a very small study that was more of a fun project, but we believe we successfully modeled for a first-time perinatal spread, and it's supposed to serve just as a springboard for future research, but as a proof of a concept, we believe it works. And it's a first step in developing a treatment response monitoring tool, because in an era of individualized medicine, this is going to be important for pretty much any tumor treatment response monitoring, because you can use this to predict how the tumor is going to progress down the road, and then based on a prediction, or you can take the prediction and compare it to the actual tumor after treatment, and based on a difference, or you can quantify the difference in days gained, which I believe is going to be the unified metrics in any treatment or tumor treatment monitoring. Our study has many limitations, and first of all, it's just a small study on two subjects, and also we accounted only for a nerve enhancement, but it's not the only change which happens to nerves infiltrated with tumor. We didn't account for nerve enlargement or other imaging changes as T2 changes, et cetera. Just a huge thank you to Dr. Spinner and Josh Jacobs, who was the manufacturing for this project, and I'm happy to take any questions.

perineural tumor spread

neoplastic lumbosacral plexopathy

tumor cells

autonomic nerves

lumbosacral plexus