New Advances in the Management of Pancreatic Cancer
Originally Broadcast: November 9, 2021 | 6:00 - 7:30 pm
Pancreatic cancer is a malignancy with poor prognosis and high mortality. The risk factors can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. During this conference a panel of experts that includes Dr. Horacio Asbun, Dr. Michael Chuong, Dr. Ripal Gandhi and Dr. Govindarajan Narayanan examine recently published trial data and review their implications to unresectable locally advanced pancreatic cancer care.
TARGET AUDIENCE
Internists, Hospitalists, General Practitioners, Pulmonologists, General Surgeons, Thoracic Surgeons, Obstetricians and Gynecologists, Oncologists, Radiation Oncologists, Nurses, Pharmacists, Respiratory Therapists, Patient Navigators and all other interested healthcare professionals.
LEARNING OBJECTIVES
Examine recently published trial data and review their implications to unresectable locally advanced pancreatic cancer care.
Identify and recognize new clinical data that supports total neoadjuvant therapy in pancreatic cancer.
Recognize the need for gastrointestinal follow-up for pancreatic cancer patients.
PRESENTERS
Dr. Horacio Asbun - Chief of Hepatobiliary & Pancreatic Surgery
Dr. Michael Chuong - Medical Director of the Proton Therapy Center, Physician Director of the MRI-Guided Radiation Therapy Program, and Director of Radiation Oncology Clinical Research
Dr. Ripal Gandhi – Professor of Interventional Radiology, Miami Cancer Institute and Miami Cardiac and Vascular Institute
Dr. Govindarajan Narayanan – Chief of Interventional Oncology
Good evening. My name is Rico Gandhi. I am one of the interventional radiologists and interventional oncologists here at the Miami Cancer Institute, part of baptist health. Um and I want to welcome you to this evening's program. Um I'm one of the course directors and in combination with Dr Horatio lesbian, who is the chief of the paramilitary surgery here. Um Tonight's session is going to be on new advances in the management of pancreatic cancer. And I think this is uh you know really serves as well as you know this month is really pancreatic cancer awareness month and there's really been a lot of advances that have been made with pancreatic cancer. We're gonna be going through some of these during this next hour and a half. We're going to start with three of our credibility surgeons at the Miami Cancer Institute including Dr Horatio has been who is the chief of the pedal be leery surgery. Um We have Dr Ramon Jimenez who is the chief of sarcoma surgery. And dr Dominic has been and they're going to start with an overview of the different surgical treatment options for pancreatic cancer. And also that's going to be followed by a discussion. I'm gonna go ahead and hand it off to you. Thank you very much Dr Gandhi for the introduction. Um I'm Dominique has been I'm a hippo to billion pancreas surgeon. I'm one of the three partners in this group. And I'm joined as you can see by Dr Ramon Jimenez and dr Horatio Azman. So we we want to discuss um new advances in pancreatic cancer surgery. And and um where we see them moving forward. We have no disclosures, no relevant disclosure to this conversation for this presentation. So three areas which have seen significant developments that have helped us provide better care over the past few decades are listed here. One of them involved. Um some of the topics that dr viscera got so nicely explained to us. Um Neo adjuvant therapy in the treatment of pancreatic cancer, particularly in borderline respectable cancer. We'll get into that in a second. Um The idea of centers of excellence that treat pancreatic cancer and their benefits associated with going to one of those centers has also been a major development um and there are a handful of other surgical events that are also improving patient care. So borderline, respectable this table that you see here is from the National Comprehensive Cancer Network um guidelines recommendations, the NCC and guidelines. Um There are a lot of details and nuances to it, but essentially uh it has to do with the tumor relationship to very important blood vessels in the area. Now, as we look at this drawing, it's a little more clear but essentially this as you are all aware of being the pancreas here in the middle. Um some of the important blood vessels that are in proximity to where the pancreatic cancer grow are circled and the when these are compromised by the tumor. Um we have to ask ourselves if reception is worthwhile for the patient in a surgical resection of pancreatic cancer. The goal is an R. Zero resection, meaning that no microscopic tumors behind and when the tumor invades these structures as we can see. Um Sometimes we ask ourselves whether or not um offering a surgical resection would benefit the patient. Um Dr Ramon Jimenez, would you care to just mention specifically some of these arteries and and how we evaluate them on a cat scan or an M. R. I. Yes. Thank you. Dominic. Ah So all these vessels. This is a medical illustration here. But when we get our imaging these days, whether it be a a cat scan with I. V. Contrast or or better yet an MRI. Ah You can see all this anatomy as beautiful as you can see it on this medical illustration. So advances in imaging technology here has really revolutionized the way we evaluate these patients pre operatively in our um Our boards we spend, I would say the great majority of the time looking at imaging studies showing this exact anatomy here and that helps us determine which patients are good surgical candidates and and which are not the vessels of interest here of course are um I don't know if you can see my cursor. I don't think you can, but the obviously the celiac axis open top here artery in red. Um There is a hepatic artery that comes out of there. There is a gastro duodenal artery that you see going south uh from that area. Those are relevant for patients who are undergoing, say, a whipple procedure. Um, the superior military artery, you see below at maybe 6:00, also very important As tumors can get really close to that vessel. And then in blue is the superior esoteric vein and up north at 12:00, the portal vein, which are vessels also that need to be evaluated pre operatively to determine whether surgery is a is a good option or not. But um, what what Dominic mentioned before? It is very important in that many patients who in the past would have never been surgical candidates today. We can downstage with chemo as as we'll talk about it in a little bit and then and then bring him to to to have a surgical option. Exactly. Dr aside, would you mind discussing some of the advantages that we've seen with giving chemotherapy first chemotherapy? Thank you. And good evening everyone. Well, it has been fantastic to see the changes that dr Lizarraga has already explained. And when I say fantastic. It's because if if as Dr Jimenez, we have been doing this for a while. Um we, for the first time, I've seen that paying credit cancer is no longer at that sentence. And that the response to new argument therapy in some patients is amazing. Um like the one that we had recently last week, we had only a six millimeter residual tumor after Neo Adjuvant therapy. Then number one. The first direct immediate benefit is that we can give more hope to the patients and that we see um people that before would not have been respectable as you mentioned um Dominic and uh and that now are approachable because of the reduction of the tumor. Um No question about that. And the uh you know, the the the amount of um as you said increases in terms of chemo completion are significant because we're giving the chemotherapy ahead of the surgery. We have several publications that chemotherapy that it is completely before the surgery and it is more advantageous because many of the patients do not follow a full chemotherapy treatment after surgery. And uh one of the other important things that that we discuss often and tumor boards is how can we assess the response to the german therapy? Um as we mentioned, different tumors depending on their on their molecular biology will respond differently to the chemotherapeutic agents we give. And so some of the things we look at is a biochemical response. By measuring the tumor marker saying 99 Um there is a correlation between higher C-99 and a higher likelihood of there being metastatic disease even if it's a cult. Um And we also evaluate the radiographic response. Now this is something that can be a little difficult to definitively say um is useful when we're trying to decide if the cancer has progressed, especially because some of the Neo adjuvant therapy uh that we use particularly radiotherapy can sometimes um induced a decimal place asia kind of a fiber optic reaction around the treated area which can sometimes look like a a progression. But that being said, what we're seeing more and more is that after a surgical resection, what appeared to be a decimal plastic reaction to radiotherapy is actually just a. I'm sorry, what what what seems to be a progression of the tumor on preoperative imaging was just a dismal plastic reaction. And so this gives us hope because whereas before you know, a a certain M Ri finding may have been um uh a bad sign for for the patient for the surgeon. Now we are realizing that that there's still maybe hope when we take that because of information in combination with everything else that that we're evaluating. Now, one question that we are still looking to answer more clearly is what are the effects of neo gene therapy on the surgery itself? And in particular does that make the surgery more difficult? So would would you two care to elaborate on on these I guess I'll ask you first dr few minutes. Yes. Um Alright, so let me do chemo and then you do radiation because radiation these days uh we'll see. We'll chemo usually chemo is going to make the surgery easier in my opinion. So I see uh smaller tumors, less positive lymph roads, some patients with complete responses. And many times when you operate a patient who hasn't had chemo if there is proximity to the portal vein, it's hard to separate the tumor from the portal vein and not legal positive margin. And once you have chemo, you improve all these different areas for me, chemo can make the surgery more more difficult. In quotation marks, in that the patient is coming to surgery with a little bit of a systemic injury they've been receiving, you know, poison therefore for a while and so they are not coming with a totally full tank. So these patients hi in terms of like intra operative and postoperative management, you need to be really attentive because missing um a little a little detailed small with infection or something like that uh can be overwhelming for a patient who's coming in already somewhat injured. So uh the chemo does make the surgery easier. But maybe taking care of the patient will be a little bit more difficult. Ah Now radiation is a different story or us. Thank you Ramona. I love you too. You want me to be the one talking about about our radiation colleagues. Huh? Um No jokes apart, radiation is more difficult. There's no question. And and it is what um What Dominic was saying? Uh the the tissues are fibrosis. They're stuck. Um And it's difficult to know sometimes what's tumor or not. And I do have to say ramon that even though I agree with you that chemotherapy makes in general more the operation easier sometimes when there has been an extensive reduction of the size of the tumor, there's this fibrosis that you don't see the vessels and where the where the tumor was. You don't see where the pancreas starts, where the vessel ends. Radiation replicates that almost in every single case, especially the type of radiation that we're doing today, um that you the audience is gonna hear from dr michael Chong and uh the results and the potential are amazing. Um, but that makes an operation more difficult. I was talking to a deal one of our other radiation oncologist today on the phone and I was telling them that you know, they should not be close to the O. R. When we're doing surgery because we keep casting at them having said that we do it with pleasure because we know that the therapies that they're doing are helping the patients as we have seen sometimes complete responses. Or as I mentioned the cases last week where there was only a six millimeter residual tumor. Everything else had had been melt away. Then having said that, I think it's a matter of us learning and when I say that is we need to learn what's the best timing to go to surgery after radiation. We have all inherited day, you need to do it between 6-8 weeks. But where is the evidence of that? And I think, you know, surgeons are so pragmatic and we inherited some statements and we follow it for years until something like this happens. And you start asking yourself Why 6-8 weeks? Where is the evidence for that? And you go back and you see that the evidence is not solid, that it was maybe somebody that mentioned it or somebody old old publication like in this case. Then we're as you know, Ramona dominate. We're trying to learn what is going to be the best time in and I'm very optimistic based on what we have already seen that we will be able to get to the to to do the surgery at a stage that it is not the one that we're seeing today. Thank you. Now, on the topic of pancreatic Centers of Excellence. Um there are multiple landmark papers that have shown that as as a hospital increases its volume in terms of pancreatic receptions, the outcomes improved. Uh This table down here at the bottom reviewed a lot of previously published papers and you can see comparing high volume centers to low volume centers, the mortality was significantly different. Um in the first paper out of New York in the mid 90s, there was a 2.2% mortality compared to 19% mortality. Um and this, you know repeats itself. Um What however we sometimes fail to realize is how much actually goes into creating these pancreatic Centers of Excellence um here dr Osborne. I'd like for you to evaluate on that a little bit. What what is it that really qualifies a center not only as being high volume but but actually a center for Excellent Care. Yes. And that is a very important point I think you know it's very interesting how across the country everybody says oh well we're multi specialty group. Oh yes we are a cancer center but the reality is um to create a true pink aquatic Center of Excellence, you do have to have a dedicated team. Um as we have done here at the M. C. I. And baptist you have to have an anesthesia group that's only the anesthesiologist that you're gonna use for HPV. You have to have a group of pathologies that have particular interest. You have to have. What I think is extremely important. And I would recommend no pancreatic surgeon goes to practice without a rescue team because we all know that despite that we may be extremely good. We will have pancreatic leaks. These are very high complexity procedures. Then it's no longer that the surgeon is the only one that has to be good. You have to have great interventional radiologists. You have to have a team. Like hopefully you all the audience are going to be able to have a feeling today. Of oncologists. Radiation oncologists, interventional oncologists and radiologists that we all interact together and gastroenterologist of course and we all discussed the cases together as we do on our board and um we developed some pathways of care. Um the as as as it is clearly stated on the slide, the communication has to be clear. You cannot just try to think, okay, just write a note on the chart or leave things and unturned and many of these things are not remunerated then traditionally, unless you have a group of people that are very committed to create a pancreatic Center of Excellence, um you won't be able to be successful and uh the the the amazing thing, those if there is people that are interested, it becomes almost like a brotherhood or or or sisterhood um that we all are working together and are able to have a feeling that we get our bags and it becomes, oh, you know what, I have this problem, I'm going to talk with the people on the board and that is extremely important to have a true multidisciplinary approach, not just one that you write in the paper for advertising, I couldn't agree more. And within this idea of creating Centers of Excellence, we have seen market improvements in peri operative morbidity and mortality I mentioned, you know, just in the comparison of a high bond versus low volume center, but overall, For the whipple procedure, for example, historically the mortality was as high as over 20 And now we expect to have a less than 5% mortality for arguably one of the most complex procedures that anyone can undergo at least in the abdomen. Um What are some of the changes that you've seen? Dr Jimenez that you that have contributed to this improvement and morbidity and mortality. I think there's many fold uh Dominic I think begins from from from choosing the patients right at our board. As we have all mentioned discussion with all of our colleagues but but picking the right patients for surgery, I think that's super important. You know, every time you see a surgical series, the first thing that is mentioned is that there's surgical bias here. Of course I'm not going to operate on poor quality patients. You know, you choose the best patients to have the best results. That's one thing. But I can you can uh forget about our colleagues in anesthesia. Some of these cases require hi attention is their high maintenance cases. You know sometimes the anesthesiologist has to be present for most of the case, not just the C. E. R. N. A. We have to have support, you know uh in the I. C. U. When it's necessary for some patients whose surgery was more difficult or they had complications or longer surgeries. Um I will tell you that one of the things that baptist offers to us is we don't really have any budget on this surgery. So so we we any equipment that we need that is going to make the patients do better baptist is there for us and uh and and as as we know now with the minimally invasive procedures, you know, there's always a new toy out there and they're not cheap and and we need them and it has never been holed up for us in terms of having all the laparoscopy tools that we need, robotic surgery tools that we need. And when we do an open case, also whatever tools we need. So I always appreciate uh our working environment here and the type of resources that we have that I know are not available everywhere. And that's a good segue into the next point. All three of us are minimal invasive surgeons. And when and as long as it's safe and feasible, we like to use minimal days, two approaches for pancreatic sections. Um dr Jimenez, it's clear that some of these benefits include shorter length of state, quicker return to work. Um There are multiple studies that show that patients that get minimally invasive approaches may have a shorter time to return to their chemotherapeutic regimens if patients have not had a new regiment therapy or not a complete of course of neo adjuvant therapy, then it's important for them to start therapy after surgery as soon as possible. Um And there are other important factors such as less postoperative pain um from the surgeon's standpoint dr human is what are some of the advantages, for example, of robotic approach to these procedures. I think uh you know, I will tell you one thing that that I know are also shares with me is that the visualization, you know the imaging that you get from a a three D. Laparoscopic camera or a robotic the standard robotic cameras also three D. But the type of close up and and the detail that you see with the with the camera is unmatched. I mean you can have you're going to be you can have uh you know surgical magnifying glasses that we call loops with the highest magnification. You're not going to have that type of detail that you get with the laproscopic and the robotic cameras. I think that's that for me is one of the biggest advantages of of the minimally invasive procedures you end up seeing better than you would see in the open case. That's super important. But I'll tell you that a lot of the the tools that we use today even for the open cases were actually developed for the minimally invasive cases. So the cases we benefited from it went backwards you know in a way. Uh But um I think I think this stuff is is uh patients requested. It's important and as long as we do as good of a job as we do in the in the standard case uh it's uh outstanding. Super. And as a good example of of that of how we can in a way almost work backwards um doing a minimally invasive surgery lets us see things and see areas that are much harder to see in an open procedure. Now this here is a diagram of the pancreas in its relation to the colon, the spleen, it's just tucked up as we all know under the left side of your ribs and it can be a difficult area to access surgically. Um The doctor asthma I'd like for you to elaborate on the clockwise technique. It's a procedure that you developed at the specific technique for accessing the digital tankers. This left side of the pancreas near where the number two is essentially. Um And how has the development of this technique and its implementation um Kind of contributed to the idea that a minimally invasive approach can lead to a better surgery. Um No, thank you the dominant for putting this up. Um This actually illustrates very nicely what Ramon has said because the minimum basic approach allows you for the magnification but also allows you for having better access to areas where open surgery. Um Yeah you can do it but it is much more difficult access and you just mentioned it very nicely. This is all under the ribs. Then normally we need to put the tractors, you know, it's just a matter of the size of the incision, particularly when you're doing a big and complex case. Right I mean and gold blathers adrenals and then the size of the incision is very important but if you're going to a really complex case, we're not doing it just to be cute and have a small incision. We're doing it because we truly believe that the minimum basic approach is going to give us advantage over the open approach. And that's the case on these dozens of total pink attack to me. And and this is not just an appreciation. Now it's pretty clear with a variety of prospective randomized studies and and retrospective studies then um if you go back a little bit to the to the prior view um if you can see the spleen, then what we do is we use the advantages also of gravity. When you're doing open surgery you can use gravity but in a very limited fashion when you're doing laproscopic surgery, you insulate the belly and you have a closed box. Then you can really rotate the patient and use gravity as your assistant on this case. We put the patient on his right side and a lateral position. And then when you start mobilizing the column, the column drops to the right and it carries along, especially in all these people, all the adipose tissue. All the fat. We do the same thing with the stomach. And then you have a very nice access to the area of the tail of the pancreas and the spleen. Just because we have used gravity to this and that allows you to do a much better surgery. And this this just highlights that this is a review of more than 360 patients that had a distal pancreatic and using that technique. And um just to emphasize the one of the important things we look at during these procedures is is the rate of the pancreatic fistula, which is where you get a continuous leakage of pancreatic enzymes from the cut end of the duct. Um and in this series again, many patients across more than 10 years. The leak rate was only 7% and that's markedly lower than the majority of other published series. And so again, just goes to show that, you know, these advances in surgery and pancreatic surgery really helping us provide better care to patients. Um Some other things that are that are still being developed are still up and coming and some of which have been around, some of which are still new. Are listed here. Um One of these for examples for us in imaging dr alan, do you want to elaborate down a little bit? Yeah, this is this is basically on the developmental stages um as you showed on the prior case when we were starting doing the the clockwise technique. We we never thought that one day we're going to be publishing 365 patients with such a great result. Then we don't know if we're going to be able to do the same thing with these new things we're doing but but so far very encouraging. We're using fluorescent imaging to try to be able to delineate the tissues better and to assess the flow to those tissues in some cases has been remarkable and have allowed us to very clearly differentiate the areas of the painters that we want to expose. And at the same time we're I'm separating what we call the unseen it process for those that that remember that it's attached to those vessels that Dominic showed at the very beginning. We we are able to depending on the time and be able to do very clearly delineate the vessels. And as you know, the surgeons, no, the separation of that part of the painters from the vessels. It's it's pretty um, it's probably one of the area of the parts of the procedure that's the most complex. Therefore, having something that allows you to visualize and identify better what's vessel and what's not has been very useful. Having said that we're still in the process of learning um what the utility is because we have seen that in some cases doesn't help us a lot at all. And that is usually impaired cases that there has been chronic pancreatitis or um, sometimes too much fibrosis because of the chemotherapy. But again, this is on the developmental stage and the beauty of this is this does not affect the patient negatively in any way. There's no, no. Um as far as we know, there's nothing that we have seen as a side effect. This is a very clear technique that has been used in a variety of other um other procedures, like on common bile duct stones or biliary identification. And we're just extending it to this. Um I think again, as we learn more about the timing and the dosage, we will be able to assess better how far this approach is going to go. I don't know if we should ask uh Dr Jimenez to talk about interpretive ultrasound and and Dominic. I would encourage you to talk about enhanced recovery. I'll be quick Dominic. The ultrasound is an old tool, but it's super useful when it comes to all of hepatic biliary surgery. A lot of us in in in surgery obviously are not radiologists. So we we we learn how to use these tools literally by during the cases. Uh But um you got you become facile with ultrasound intra operatively and it definitely helps you to plan for the surgery, improve your margins, even determine the order in which you get things done during the operation. Uh And so the ultrasound, even though it's an old is older definitely than, say the the fluorescent imaging. It still has a big role. I think for a lot of our cases definitely um enhanced recovery after surgery is it's sort of a general term for many advances that are bundled together. It's there is data from the early 1990s that showed that a lot of the things that we used to do as surgeons were. Not based on hard evidence, but just on tradition in a way our surgical dictum as doctor, as I mentioned earlier. And so there are a lot of changes, for example, to when you start feeding someone after surgery um that were attempted and found to be beneficial to the patient, especially when used in conjunction with other similar changes, limiting how much narcotics patient might get after surgery. Um You know, early amputation after surgery, etcetera. And so they seem like simple things. But it's it's remarkable how many different aspects of the patient's postoperative recovery are improved when these things are all used in conjunction. Now again, this kind of highlights the importance of being at at a a center of excellence for cancer care because um we have available to us the resources, the protocols that we need to make sure that all our patients are getting this type of recovery. Um And these enhanced recovery protocols actually begin even before the surgery with certain amounts of patient education. Um It has to do with how things are given during the surgery as well. Um And so all in all this has been a huge change in in all all fields of surgery. Um But especially pancreatic cancer care, we we really have seen the benefit. So that ends our our discussion. Thank you all very much for being present. Thank you very much. Really, really nice overview on all the advancements, advancements in pancreatic cancer surgery. You know, I have to tell you the first time I saw a patient after a minimally invasive pancreatic whipple surgery. I was impressed the patient had just a few little incisions. I honestly didn't even know that that could be done in today in the modern day. So it's really, I think a tribute to some of these techniques and and to our surgeons here. Um it's my pleasure to move on to the next speaker is dr Michael Chong. He's the Medical Director of radiation Oncology here at the Miami Cancer Institute and he has a lot of expertise and experience in treating gastrointestinal malignancies, including pancreatic cancer. So I will go ahead and hand it off to him. Hello everyone. It's really a pleasure to be here with you today. I'm Michael Chong. I'm a radiation oncologist with a focus on treatment of gastrointestinal cancers here at Miami Cancer Institute. Uh and really the goal of the over the next 10 or 15 minutes or so that will be to share with you some of the exciting data that has come out of several institutions, including ours around a blade of radiation therapy using an MRI guided radiation therapy delivery technology and technique that is really revolutionizing how radiation therapy is delivered fundamentally, especially for very challenging to us. Like pancreas cancers here are my disclosure is really the only relevant one is my relationship with view a around research. Uh and as well as my participation on their advisory board. So to give an example of really the application of em are guided radiotherapy and dose escalation using that platform. Let's go through a typical case that we might see in our clinic. So this is an 80 year old gentleman who was referred to the radiation oncology department here with an unrestricted locally advanced tumor in the pancreas. You can see quite extensive vascular involvement here of the of the S. M. A. Conf iliac access. So this patient initially received full fear knocks had local progression only and then was referred for radiation therapy. And as it is typical in really any modern radiation therapy center, a simulation CT scan is performed which gives us the anatomy to develop a treatment plan. And you can see here that there's uh normal organs that are defined as well as the target which is the gross disease. And then there's a treatment plan that's generated um very highly informal, highly targeted treatment just to the areas at risk. And when the patient comes for treatment there are ways to generate CT scans on the treatment machine. Something called the cone beam cT. And you can see here that there is a soft tissue definition here. But the image quality really is not the same as a diagnostic scan. And certainly not as good as the simulation CT scan used for planning and this is really the state of the art at most centers and really is is a standard of care for image guidance. Now we've imaged the patient beforehand. We've made positioning changes in their in their and how they're set up on the machine. And now we go to image during treatment to ensure that that has been maintained but that in fact does not exist with current Lennox or current radiation delivery machines. In fact, this is actually sort of what we see in a way uh in that this is the treatment platform or the treatment console rather. And we can see the patient lying on the machine, the machine moving around the patient. But actually the internal anatomy is not visualized with standard CT guided radiation therapy. And when the patient comes for again the first day of treatment, that original treatment plan is delivered and when the second day of treatment is is delivered, the same thing is delivered and so on and so forth every single day. But we of course know that the anatomy each day will not remain the same. And there will be some small but potentially large variations in the anatomy and this is really not able to be accounted for in a short period of time on a day to day basis. And therefore it's really a the same treatment is delivered each day regardless. Now, of course not being able to visualize inside the body during treatment is certainly not ideal. Uh and this is obviously a bit tongue in cheek, but effectively the limitations and what I described to you in terms of imaging are not being able to image during treatment in some limitations with the quality of soft tissue imaging with cone beam cT has led to nonaffiliated radiation dose being a standard of care for uh for a long period of time. And again, even today, nonaffiliated radiation therapy is a standard of care at nearly all centers To give it a sense of the outcomes from this approach after chemotherapy with Nana bladed radiation, whether it's with standard fraction ation treatment from the lap 07 randomized trial or with lower dose um S. P. R. T. So somewhere in the 33 or 30 gray range and five fractions, we can see that two year survival really is quite poor around 20% or so. Now there has been emerging data uh and for example, this one study from MD Anderson published in 2016 that suggests that perhaps in highly selected patients where a higher dose could be safely delivered. Because again, the anatomy here is very important to consider given that the stomach and the intestines sit if not a but the tur and these organs at risk really are not very tolerant of high doses of radiation, but nonetheless, higher doses of radiation and for some patients seems to pretend seems to potentially improve, not just look controlled, but also excitingly overall survival. And in this study, A biologically effective dose of over 70 gray. How was associated with a with an approximate doubling into your survival. So of course, very exciting. But clearly more data needs to be generated to to support this as a, as a relevant strategy for a broad population of patients. Now obstacles delivering a blade of radiation dose are those you can see listed here soft tissue resolution of course, as I mentioned before, is limited with C. T. There's respiratory motion of these tumors that need to be accounted for imaging during treatment. Again, it's not possible, there are some uncertainty margins that are inherently used and this can overlap the bow and the stomach and that can limit how much radiation dose we can give. And there's also again an inability to account for changes in the stomach and bowel position prior to each treatment. Now, MRI guided radiation therapy really overcomes all of these obstacles and directly addresses all of these um all of these challenges. And we are proud to feature the meridian line ac, which is the second clinically operational eh marlin back in the United States beginning in 2000 and 18. And this is one of many state of the art radios and therapy platforms that we offer patients here. And really this is very unique and we are not aware of another center actually in the world that offers the complement of state of the art radiation therapy machines that we do here and this really allows us the opportunity to personalize the radiation therapy options for each particular patient, whether it's a pancreas cancer patient or a breast cancer patient or a brain cancer patient uh and for pancreas cancer patients, the meridian line ac has become clearly our treatment of choice. And I will show you why so inherently M. R. I. Scans provide superior self tissue resolution compared to C. T. And this is these are images from patients treated here at our center. And you can clearly see that scans obtained with uh CT scans really. You can not nearly as well define the internal anatomy. MRI. And I will play this video here. You'll see another really important capability of of an M. R. Clinic is that there is continuous imaging with an M. R. I. Scan throughout the treatment. So, remember with standard radiation machines using CT scans, this is not possible even just to get a one static in. So this is with MRI a real time what's called a Sunni M. R. I. That's obtained throughout treatment. And what you see here is an example of how when the this is a saddle view here tracking the pancreas. So you can see that this is actually a capability in which soft tissue can be automatically tracked by the system. And what you're seeing here is that there is a boundary or a margin around where that tumor uh sits in one position and so when that tumor moves because of respiration and it moves out of that boundary. The machine recognizes this as having moved and the machine automatically will turn off as a safety feature. And also we don't want to, you know, obviously treat the intestines when the tumor has moved. Uh And this is something that is automatically again recognized by the by the treatment machine. And when the tumor comes back into the right position that the treatment will automatically turn back on. So this is an automated process, which is very unique. This also allows us to treat a much smaller volume of tissue because we can now have the certainty uh that we know where the tumor is at any at any given time. So again, with the typical paradigm of of treatment delivery, we remember we we typically will give the same treatment each day regardless of the changes in the internal anatomy. With an M. R. Linux Mac. We're able to now repeat that whole process each day. So there's a simulation each day essentially. There's new images, uh the organs at risk and the tumor is redefined each day on an M. R. Linux Mac. There's a new plan that can be generated. There's a the independent QA process and then delivery of a brand new treatment plan each single day that can account for these changes in a short period of time and on a daily basis. And this really allows for a personalized radiation therapy treatment and really the most accurate treatment. And you can see here for across five days of treatment. For example there can be significant changes and we can we can address that priorities treatment within a few minutes. And this is really unique and and a significant tool to allowing us to achieve significant dose escalation to to patients with these types of challenging tumors. Also very beneficial for the patient is that this is done as an outpatient Really in total each day. Accounting for all of the assessment and replanting of treatment and delivery. It takes about 45-60 minutes per day. Most treatments are delivered in five days but can be done in less than that. This is entirely non invasive. There is no anesthesia or even an I. V. For I. V. Contrast. Uh There is really no patient downtime. So patients typically will be able to work or or carry out their normal activities. And this is really ideal for patients traveling from a great distance for treatment. And we do have a significant population of patients will travel across the country or even internationally for this type of high dose unique short course radiation therapy. Now this is all great that we can do these things. But does it actually matter. And so the data that are emerging suggests that in fact this matters quite a bit. This is a retrospective study from several institutions using the technique that just described to you something called adaptive memory guided radiation therapy for inoperable pancreas cancer. And long story short as they also looked at outcomes based on the dose delivered with the higher dose being achieved using these very sophisticated M. Ri adaptive type of techniques where the treatment is modified each day and the monitoring is done during treatment And similar to the M. D. Anderson study that I showed you before there was a statistically significant improvement for the higher dose patients with to your survival being about 50% versus 30% in a standard dose group. Also exciting was that despite the higher doses that were delivered there in fact were no grade three toxicities or higher in the higher dose arm. And in fact in the lower dose cohort there was there was some toxicity and and that perhaps is because those patients were not offered or were not delivered treatment with the adaptive component. The the the the replanning each day component because it was at that time felt not to be needed because it was a lower dose of radiation. So perhaps the adaptive component matters. You know, we were really the first institution that published Outcomes of inoperable pancreas cancer patients treated with a dose escalated a blade of regiment in five days On an M. R. Linux Mac. And this was published in 2020 in a fairly small number of patients 35. But the early outcomes here showed that there was really no significant toxicity associated with this in the early outcomes were very encouraging and I know the text is small, but um, but really the the exciting longer term follow up results of that I want to focus on here. And these were data presented at astro earlier this year in Madrid. And this was a 50 consecutive patients series treated at our institution. I won't read through the demographics here, but you'll see that the majority of patients had locally advanced disease had good performance status. Had a very high prescribed dose. This is 50 gray in five fractions for a biologically effective dose of 100 grand for those of you who are not radiation in colleges. This is upwards of twice the prescribed dose that that is typically given with with various fraction nation schedules on a standard Linux. The media follow up was 18 months from diagnosis. Uh and we were very excited to see the outcomes. So local regional control was a meeting of 32 months and at two years was almost 75%. Overall survival was a meeting of 21 months was of course we were thrilled to see with the historical outcomes being somewhere in the 12 to maybe 14 month range with standard radiation doses. But also exciting was that we were seeing a hint that in fact the two year survival mark, In fact was significantly better at least than compared to historical control of 20%. And we saw in our series um an estimated to your survival of 50% And also very exciting to us was that the grade three toxicity rate was very low. So acute 2% in late 10%. And there was no grade four or five toxicity so very well tolerated. And the efficacy, outcomes with longer follow up seemed to be very good. Now why does this matter and why, why why might we be seeing these outcomes? And in fact it turns out that patients with pancreas cancer die of metastatic disease of course. But even those who have made a distant metastases can have significant morbidity and also mortality from local progression. And this is a really pretty well known study from the johns Hopkins group of a rapid autopsy analysis of 76 patients documenting that about one third of patients will die of local progression or consequences of local progression despite the presence of distant metastases. So perhaps if we're able to achieve better long term local control, this may meaningfully impact long term survival. So this is um this was actually an email from a patient's daughter of mine who received this a plate of M. R. I. Guided radiation therapy. And it really is rewarding to see that this type of novel treatment directly impacts patients. And and you know, she wrote to me and said that mom has been doing better than ever. Her pain is greatly improved. She's eating better and feeling well. Uh They just went to Hawaii where they hiked diamond head crater and did all these other fun things six months ago, we didn't believe that these things would be possible. But now we believe that anything is possible. Uh and uh it's just incredible how much better she has been doing after the radiation therapy. So she really had a tremendous uh response to treatment and have a meaningful I think long term tumor control outcome and she had really a great outcome. Um And this is not representative of just a small percent of patients but really very common to see in patients and Philip oversee this treatment. There are perspective trials ongoing. Looking at this very exciting and novel type of treatment. There's something called the smart trial which is an international trial, looking at this five treatment regimen using a blade of dose. Uh And um I was fortunate enough to be um invited to be a part of the national P. I. Group for that. So this trial will be closing to a cruel hopefully by the end of the year and we should have the results of that early next year. So in conclusion, MRI guidance represents a paradigm shift in radiation therapy. A blade of dose can be delivered for pancreas cancers as well as others and challenging an atomic locations. And there really are very unique applications of this for other cancers that I don't have the time to go over today. But really exciting that we can benefit a broad group of patients including pancreas and other cancer patients. There is increasing evidence that this is critical for inoperable patients can't potentially prolong survival. Uh And again the smart trail is the first prospective evaluation of this approach for inoperable patients and will again complete a cruel likely later this year with that. I want to thank you for your attention. Thank you very much. Dr chang very nice overview of some of the radiation therapies for pancreatic cancer. You know, as as you mentioned, you know here at the Miami Cancer Institute we have the most advanced radiation technologies in the world which is which is quite impressive while surgery is the standard of care for patients who have respectable pancreatic cancer. Unfortunately the majority of patients do not. And therapy such as radiation, some of the therapies that that you showed during this talk I think are extremely optimistic and have the potential to really improve survival for some of our patients. I'm gonna we're gonna move on to our actual, you know, actually I see that there's actually a question here and um you know, but I think maybe we'll go ahead and respond to respond to this question um you know, via via text and we'll go on to the next talk. The next talk is by dr raj Narayan and he's the chief of interventional oncology here at the Miami cancer institute. He's also a world expert on utilization of Ira or also known as nano knife. The technology for the treatment of pancreatic cancer. And I'm gonna go ahead and let him do his talk. Thank you. Thank you, repo. Good evening everyone. It's my honor to be a part of this esteemed group of faculty members here, my colleagues at the Miami Cancer Institute and my partner, dr Gandhi, my name is raj Narayanan. I'm an interventional radiologist, practicing mostly uh oncology and heading the international ecology program at the Miami Cancer Institute and the Miami cardiac and vascular institute. So these are my disclosures and I'm consultant for Angie dynamics, the manufacturer of the device. The nano knife which we're going to talk about. Universal electric preparation is a new kid on the block. It's been around for close to 12 years now. And this is a technology that uses high worked, its low energy dc current to electrocute the tumor cells. And use of this technology in the pancreas is considered as an off label use in the United States. So this is the only universal blood preparation device that's available commercially. It's called the nano knife. And on your left you see the generator in the middle, you're seeing the probes are electrodes that we use. You need at least two of these to create a treatment zone. Um and you can use up to six of them which can be connected to the generator and on the far right. You see what's called the accusing device. And this device um is used to synchronize the patient's E. K. G. Because we're delivering 3000 volts of electricity. This could cause a possibility of irregular heartbeat and this accusing device. Once it's gated to the patient's E. K. G, it detects the rising slope of the RV. When the cardiac cycle, it sends a signal to the generator and the electrical pulses delivered during the refractory phase of the cardiac cycle. And thereby it reduces the risk of cardiac arrhythmias. When you're using two needles, you need at least 70 pulses to complete the treatment. And depending on the number of needles you use, you're going to have that many pairs that I used to treat. Here's an example of a cartoon showing you pancreatic cancer which is encasing the artery and the vein and the numbers depict where the needles are placed. This procedure is done under general general anesthesia and with cat scan guidance and it can also be done in the operating room in an open fashion as it's done some other centers. When we use the per cutaneous approach, we use cat scan guidance and general anesthesia and these numbers depict where the needles are going to be placed to bracket the pancreatic cancer And once we turn on the machine now you're going to see up to 3000 volts being delivered to one pair and once that treatment is completed, the machine automatically switches to the next pair an expert and you can add and subtract players depending on the size of the tumor. And this is how the entire treatment is completed. So what are some of the complications from this procedure doing this practice Heinously with imaging guidance, the needle placement has to be extremely precise. And unlike open surgery we do not have the advantage of being able to move structures and place the needles with direct vision or with ultrasound guidance. So in this particular case this patient had a colon that was anterior to the tumor that was supposed to be a plated. And while we used the compression device to move the colon out of the way, as you can see in the middle. While we advanced the first needle and a few minutes we noticed that there was a hematoma or bleeding from one of the small veins which was in the path of the needle. The procedure was aborted and the patient was managed conservatively. But this is just to highlight that we're dealing with one of the most vascular territories in the body. And while the technology is safe near blood vessels, it's critical that the placement needs to be very precise or else you could have catastrophic bleeding with the patient on the table. And the other possible complication with this procedure is pancreatitis or inflammation of the pancreas. This is something we did not see much in patients who have had previous radiation. But if a patient is getting the noble I. R. E. Um And this is a possibility. Usually we have these patients admitted overnight for observation and they maintained without any feeds and we repeat their amulets and light based levels in the morning. And if we notice that there's an elevation we keep them without any feedback and just maintain them on ice chips. And usually the numbers trend to normal within a day or two. But that is not a common complication. But this is something which can be expected. So let's look at some of the data that supports the use of this technology. And we'll start with just going to deal with the Park Catania Sayyari data even though there is a lot of surgical data on the same topic. So this was the very first human data that I published back in 2012. This was a small series of 14 patients. It was a retrospective study and we managed to downstage two of these patients who were considered inoperable and got them to surgery. And they managed to have a what we call as an R-0 margin. Um So that was an exciting start for this technology. And uh we wanted to advance this further. And in 2017 we published another retrospective cities looking at 50 patients now who were all treated with irreversible preparation and these patients had stage three or locally advanced pancreatic cancer. The primary objective of the study was to assess the safety profile of the procedure and the secondary objective was to determine the overall survival. And all of these patients have prior chemotherapy and About 60% of them had previous variation treatment. And we followed these patients with seated one month and three month intervals and the median time from diagnosis to Ira was 11.6 months. So the results, we found that the median overall survival was 27 months and the from the time of diagnosis and 14.2 months from the date of I. R. E. And there were no treatment related deaths or 30 day mortality. So this is a significant improvement over what is conventionally the numbers that you would have with just chemotherapy alone or maybe with standard chemotherapy and radiation. So based on this study, we concluded, who would be an ideal patient for protecting his diary And that would be somebody with stage three or locally advanced pancreatic cancer. Somebody with a good performance status. We call that as the peacocks grading. Somebody with peacocks status of 0-1 and a safe access to reach the tumor. Once again, when you're doing this by continuously, you would need a safe access And somebody who has completed at least one line of induction chemotherapy and one of the variables we look at in this retrospective study was the size of the tumor. And we found that patients with tumor size less than 3cm be or less did better than those who are over when we compared the per Catania's experience with the largest surgical experience, which was from DR martin's group In Louisville, that was multi center study, which looked at over 200 patients. Uh you can see that there are two lines in the surgical study and that depicts a group of patients who had just ira alone. Another group of patients who had Ira in the operating room to accentuate the margin um to help them to get a clean margin when they're doing the surgery. So compared to this group, the retro the pancreatic protectionist group and overall survival, which is comparable or slightly better of 27 months compared to the overall survival of 25 months with the other study. Now, this retrospective experience that we had was also duplicated in other centers around the world. And this was a study from the United Kingdom that was published back in 2018 from Dr. Eddy Line and Heartbeat Persons Group. And uh they looked at again, patients with pancreatic cancer that were treated with irreversible electro operation. And this was 75 patients were retrospectively analyzed and they found that the median overall survival and progression free survival post I ari was 27 and 15 months respectively. And four of their patients that were treated were all downstage to surgery and to an R zero R zero resection in three patients, another small group in Japan. And this was interesting in the fact that even though they only treated eight patients, they did four patients in the open approach and four of them in the park cutaneous approach. And the median time the local progression after IRA in this study was 12 months, Median overall survival after Ira was 17.5 months. And median overall survival from diagnosis was 24 months. There are four major complications in three patients and no patient deaths within 90 days post i. r. e. So when you look at the comparison of four of the major retrospective studies, one was that was one of his perspective which is dr manning's group. Uh the other three retrospective. When you look at the overall survival and from data via three and from the diagnosis, you can see there is a signal and these ranges are between from 10 to 17.5 months from the date of ivory and uh from diagnosis you have 17-24 months. But what is clear from these different studies from different parts of the world that there is a signal where we see that these patients could have improvement of their survival. Again, one of the limitations of three of the studies was they were retrospective and patients by selection bias comes into play and many of these patients have done better than what typically would happen in conventional patients. There's a couple of other studies from different parts of the world. This one is from china that looked at patients who received just chemotherapy along with gems side of being. And compared that with a group of patients who received both chemotherapy and irreversible electro operations. About 33 patients received i. r. e. and chemotherapy and 35 patients had Jim side of being alone. In this study, the overall survival was much better in the combination group. They had an overall survival of 19.8 months versus 9.3 months in the chemotherapy group alone. And progression free survival was also better 8.3 months versus 4.7 months. And the study concluded that adding I ari to chemotherapy would help in patient survival. Again, the limitation of this study was that they used to stem side of being which is currently not the standard of care in patients with good performance status. Um They would go to a combination treatment with fall free knocks First This study is from the BMC Cancer Journal which looked at a propensity score matching analysis of patients who had induction chemotherapy and then received either conventional radiation therapy or irreversible electro operation. And they had about 32 pairs of these patients who were studied and they found that there was improvement in the progression free survival in the patients who received chemotherapy plus I. R. E. Compared to the patients who had just chemotherapy and radiation once again this is to be clear this is conventional radiation. These patients at 67th grade in 30 daily fractions over six weeks. This is not the mm marlin treatment that dr chang alluded to earlier. But they noticed that the group that got Ira plus chemotherapy did better than the group with conventional radiation. So after 10 years of this treatment being done in a off label basis, the FDA finally granted the permission to perform the first randomized controlled trial and in a prospective fashion to get level one evidence. And the direct study was born. And this study is currently enrolling patients and the monitor service. One of the pieces along with dr rob martin who's with both the national PS for this study. And this study is a single study with two protocols. Not only does it have randomized controlled trial, there's also a control registry to get a high level of evidence. Both from the level one evidence and also a real world evidence from the registry. And both of the border RCT. And the control registry would have a control arm. And the overall survival is would be the end point. So all of these patients would have to meet the study inclusion criteria. And after induction chemotherapy with paul three knocks. They will be randomized to either more chemo therapy or chemotherapy plus I. R. A. So what are some of the future directions for this technology. Uh As one of the few centers that offer this treatment option along with all the other treatment options that you saw. Were excited to not only look at the potential for this technique today, but also what can be done in future. And one of the key limitations for chemotherapy it with uh in pancreatic cancer is the effect of the stromal tissue and the problems with the got penetration into the pancreatic cancer. And one of the key drugs is the immune checkpoint inhibitors and the study from the MD Anderson group, where they looked at use of irreversible event preparation and the mice model. They found that this technology reverses the resistance, the immune checkpoint blockade and pancreatic cancer. And again a signal to what could potentially happen in the future when combining this technology with conventional or existing chemotherapy options. So in summary Irreversibility Corporation is a blade of technology that uses high voltage low energy dc current. It's been shown to be safe near blood vessels but of course when using it near blood vessels, needs to be a high level of precision. Um prospective and retrospective studies have established the safety of this technique and multiple studies have also indicated a survival benefit and currently we have a registry and randomized control trial that is recruiting patients which will also help further defined role of I. R. E. In the treatment of pancreatic cancer. Thank you very much. Roger thank you for that very nice overview of I. R. E. And it's really really promising role for pancreatic cancer. Um we're gonna move on to the next talk. This is gonna be a topic that I'm gonna be reviewing. Its utilization of an innovative approach utilization of intra arterial chemotherapy for pancreatic cancer. These are again patients who are not surgically respectable. These are patients in whom we're trying to prolong their life. Similar to some of the patients that dr Narayan and uh and uh dr Chong demonstrated. And this is a innovative approach which is currently under in a clinical trial and we happen to be one of the clinical trial sites for the technology. So we're gonna go ahead and launch into the presentation here. Hi this is rob Riggle Gandhi again. Again, I'm an interventional radiologist, interventional oncologists at the Miami Cancer Institute. And my talk is going to be dedicated to the potential future innovative strategy of utilizing intra arterial chemotherapy for pancreatic cancer. These are my disclosures, although none of them are relevant to this talk. This is our team and this is our center objectives here are going to be reviewing pancreatic cancer again, although it has been discussed as well as well as locally advanced pancreatic cancer. We'll be talking about treatment of locally advanced pancreatic cancer with intra arterial gem cited. Bean and the mechanism of action. Review the clinical data And the future direction of the Tiger Pack Phase three randomized clinical trial. This is pancreatic cancer. When we talk about it. It is the third leading cause Of cancer death in the United States and is projected to become the second leading cause. By 2030 There's over 50,000 new cases in the United States per year and over 300,000 cases per year worldwide. We talked about staging Um the ones that I'm going to be focused on is stage three, which are the locally advanced, which makes up about 35% of the population. 15% of patients have those tumors which are respectable. And then unfortunately 50% of patients present with metastatic disease. Again, the ones that are really the focus of the stock are the ones which are Stage three and typically those are patients who have disease which is involving either the superior Mesen terek artery or the celiac access with greater than 180 degree involvement or smb or portal vein involvement, which is not a minimal to surgical reconstruction. Only locally advanced pancreatic cancer patients can have just some local pancreatic lymph nodes. But if you have more than those lymph nodes, then those patients will not be eligible either. And what is the standard of care for therapy For stage three disease? It tends to be systemic chemotherapy alone. And currently, best standard of care results in about 15 to 16 months median survival in patients with Stage three disease, which is, you know far worse than that with Stage two disease where you forget about it. 20% 5 year survival problem with systemic therapies such as jump side of being or not, paclitaxel. Also known as abraxane or with different thoughts is that you cannot deliver high doses of chemotherapy actually to the pancreatic cancer itself because of limited drug penetration. And then if you want to go with very high doses, you're going to have issues with systemic side effects. So survival for pancreatic cancer is only minimally improved over several decades. So we really need advances in therapy urgently in this in this area. Local control appears to be important for symptoms and survival in patients with locally advanced pancreatic cancer. And you've heard about potential means for local control, including radiation and I. R. A. Other options include gene therapy, high intensity focused ultrasound tumor treating electrical fields. But but what I'm going to be talking about here is a means of overcoming this technical problem which is present with systemic chemotherapy regimens which have limited efficacy and hyper vascular tumors. Here, here's a patient and there's a schematic with the patient with a hyper vascular tumor like HCC or hematoma. And these patients are very highly vascular rise. And you can actually access these blood vessels and deliver high dose chemotherapy or other treatments such as radiation directly to the tumor itself. However, when we look at hipaa vascular tumors such as pancreatic cancer, you cannot actually identify the tumor feeder vessels. So it's hard to actually deliver the systemic therapy or even to target therapy directly to these tumors. And you cannot actually identify the tumors, the temporal blood supply. And again, here's just another case example. Here's a hematoma very well vascular rise, you can see the blood vessels and you can deliver a high doses of therapy directly to it. However, this is completely the opposite and pancreatic cancer where you cannot identify the tumor tumor blood vessels at all. So this is really an area for opportunity. So one possible solution is trans arterial micro profusion, also known as you know, go temp. And this um therapy basically allows for targeted delivery of high doses of chemotherapy or other systemic agents directly to the site of the tumor. And basically there's two balloons which I'm gonna show you in this uh a little video. But basically you deliver the chemotherapy between these two balloons and you could deliver high doses of chemotherapy directly to the tumor. So you basically isolate the actual blood vessel where the tumor is located with this Lenovo catheter device which is introduced through the artery and directly to the side of this tumor here. And basically you can change the distance between these two balloons and now you infuse the systemic therapy between the two balloons with the goal to isolate that therapy directly to the site of the tumor itself. You want to get rid of any non target blood vessels. So again here, you can adjust the location of balloons. And again, infuse high doses of chemotherapy directly to the site of the tomb. So the blood vessel itself is isolated such that you can after you isolate the blood vessel. You can increase the pressure across the blood vessel wall and actually overcome the actual um pressures and therefore deliver high dose chemotherapy directly to the tumor itself. So what has been shown is after you put up the first balloon and the second balloon when you get to about 45 mm of mercury pressure, the tissue pressure is overcome and you actually overcome the actual um interstitial pressures of the tumor itself. And that was the chemotherapy to actually get into the tumor itself. And this is just a little you know schematic showing that. Now what has been shown is you know when you deliver this chemotherapy there is microvascular wash out through the venus outflow. But some of the studies have shown that radiation actually reduces the venus outflow by decreasing this microvascular washout. So again this here's the washout and the radioactive radiation actually eliminate some of this and this leads to more diffusion of the intercultural chemotherapy directly into the tumor itself. Again this is a number of schematic showing but essentially the same thing we're delivering the high dose chemotherapy directly to the tumor. Here's a case example there's a patient with locally advanced pancreatic cancer which involves both the common hepatic artery and the superior pheasant eric artery as is shown on this um C. T. Scan with this renewable catheter. You're isolating the chemotherapy here both to the common hepatic artery and the S. M. A. Delivering high doses of chemotherapy directly to the. So what are the clinical trials? And the results are thus far with this device? R. R. one was initial dose escalation safety study and it should looked at safety and the maximum tolerated dose and dose limiting toxicity looked at 20 patients with 101 treatments. This was followed by A. R. R. Two observational registry. The primary endpoints being survival and to moral responds. And 25 patients were treated with nine total 96 treatments. And um and this is the published study here. What was found in these first two studies, 43 patients were treated mean age being approximately 70 years on nearly half the patients actually over half the patients had some type of therapy prior to the cultural therapy which included either chemotherapy or chemo radiation. In most patients, the median jump site of windows being 1000 mg per meter square Average treatment and each patient was about 4" arterial therapies With about 13 patients receiving the actual planned aid treatment Reasons for early discontinuation included two more progression serious adverse events or a physician or patient preference. Now these are the initial promising data from the Phase 12 studies as well as the observational registry. So if you look at the median overall survival and the patients who received at least two therapies of intra arterial chemotherapy in combination with radiation, median overall survival was 27.9 months. Now you have to compare that to what is our best survival right now. If we look at you know, jump cited being in abraxane you know in combination here You're looking at a median overall survival about 12-15 months. So we are nearly doubling the median overall survival with this intercultural therapy at least in these early studies. And the CT imaging really provides a simple approach. The vasculature allows you to identify the tumor and the vessels that you want to target with this actual therapy. Here's a case example. Here's a patient with the 3.3 centimeter tumor who was treated with this device and you can see that the C. A. 99 tumor markers have a significantly decreased um following the therapy as well as the tumor on subsequent imaging studies. What are the limitations of these previous studies? Well, relatively small number of patients non randomization. There's always the possibility for selection bias. So this has led to this phase three randomized clinical trial, the Tiger Pack study which is is going to study or is studying the efficacy of this approach. So this is a prospective multi center randomized clinical trial which is comparing intra arterial chemotherapy to systemic chemotherapy for locally advanced pancreatic cancer as defined by the N. C. C. M. Guideline with the primary endpoint being overall survival. Secondary endpoints are listed here. The goal is to enroll about 300-350 patients. That's with the ultimate goal to enroll randomized 200 patients because there's gonna be a certain number of patients who are lost during the induction period. Initially patients get ivy, genocidal bean or practicing for two months and get imaged after that. If they develop any progression there they fall out of the study then they get radiation therapy initially was with I. M. R. T. Or S. P. R. T. But the initial protocol allowed um you know both both of these. But what was shown in the pre clinical studies that S. P. R. T. Was shown to produce higher levels of microvascular destruction and for for better patient experience. So the study protocols being is in the process of being modified. But after radiation therapy patient gets another month of john abraxane and is restaged after that if they have disease progression they again fall out of the study and only then our patients randomized either to systemic chemotherapy alone or to intra arterial chemotherapy which consists of intellectual delivery of genocide of being every two weeks for a total of eight treatment. Again with the primary endpoint being overall survival. And what has been shown so far if you look at the systemic levels of genocide have been they've been reduced by nearly two thirds by in the form of a kinetic studies compared to systemic chemotherapy. And this is really relevant. And you know, I've treated several patients as a part of this clinical trial and the patients have very few side effects from the inter arterial delivery. And that's because most of the chemotherapy is being delivered locally directly to the tumor and there's very minimal which is going systemically and therefore patients don't have the same side effect. So in conclusion, localized intra arterial chemotherapy utilizing this catheter demonstrates encouraging results in stabilizing the local disease. And benefit is especially pronounced in patients who have prior radiation therapy In this phase three randomized Tiger Pack trial of which the Miami Cancer Institute is one of the participating sites will provide definitive evidence whether this therapy provides survival benefit and will change the standard of care for patients with locally advanced pancreatic cancer. And I'm going to consider there. I want to thank you for your time. We're gonna conclude this session. I was hoping to have a little bit of time for Q. And A. But I you know, I want to be respectful of everybody's time. But you know, I think I just want to conclude with I think there's a lot of optimism for pancreatic cancer. There's been a lot of advances as you've heard with systemic therapy, radiation therapy, surgical approaches and minimally invasive treatment options including I. R. E. And inter arterial chemotherapy for pancreatic cancer. I encourage you to you know seek you know more information at the Miami cancer institute if you have any further questions regarding any of these approaches. And I want to thank the distinguished faculty that, you know, give up some time to give these lectures tonight. Thank you very much and have a good evening.
