Experts in pancreatic cancer research, gastrointestinal surgery, medical oncology, nurse navigation in oncology and endoscopic research discuss the treatment of pancreatic cancer at Penn Medicine.
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Twitter @PennMDForum Dr. Beatty’s physician profile Dr. Ben-Josef’s physician profile Dr. Teitelbaum’s physician profile Dr. Binder’s physician profile Dr. Lee’s physician profile Dr. Kochmans’ physican profile Recent Advances in Oncology Cancer and COVID-19 Vaccination | Penn Medicine
seriously. Hold on one second. I just started it dr taliban. Yeah, we are live. So just give a few minutes here. Uh huh. What? Okay. Mhm. So we're gonna stop start at the top of the hour when I really want to welcome those that are starting to log in. Um this is actually really exciting for us um uh and to welcome you on behalf of penn medicine, the Abramson Cancer center, Pancreas cancer is increasingly complex. So when we envisioned this talk, we wanted to speak to some of the innovation that's making it a much more treatable disease. Um it used to be someone you know, was diagnosed with pancreatic cancer And you know, you if they were surgical, you rushed them to a surgeon, got it out and then try to cope with it later. And now there's a much more um complex approach to a locally advanced cancer and even a metastatic cancer. Um my questions to the surgeons now our surgical now surgical ever, surgical later, surgical never. And and the complexity is really reflected in our multidisciplinary conferences where we can spend 15 or 20 minutes um discussing and sequencing the approach to a case. So it's an exciting time to talk about some of our innovation um in this space, going to wait one more minute and and then we'll probably get going in the interest of time. There is a question and answers at the end. We're going to try and protect 10 dedicated minutes to this so that we can really hash out, let everyone speak and then address questions that come up as we go along. All right, so my clock is reading seven. my name's are seeing a title bomb. I'm a medical oncologist. I'm going to moderate this session today. We have a really exciting panel of speakers um discussing updates and pancreatic cancer and really our team approach to complex care, a very multidisciplinary approach. Um Again, I'm a medical oncologist, I'm the clinical director of the pen Pancreatic Cancer Research Center. And actually if you could advance the next slide, I'll introduce our panel today. That's me at the top left. Um We have Trish Gambino who's going to lead off the discussion. She's our dedicated pancreas cancer nurse Navigator. She's often the first touch point for a patient with a new diagnosis of pancreatic cancer and she's expert in sequencing, who patient sees when and working to get a diagnosis. Um And it's often the first person that patients or and referring physicians will speak to. Second speaker is major Kenneth lee. He's a a surgical um oncologist, assistant professor of clinical surgery, really expert. Also helping us figure out, as I like to say, surgery now, surgery, later surgery ever, surgery. Never, which is really a thing now for some of these patients. Um, and speaking of some of the surgical innovations, Kim Rice Bender is one of our active medical oncologists try lists really. I'm going to describe some innovative trials in the in the attempt in the curative intent space and it's really exciting to be able to say pancreas cancer and cure in the same sentence. Um, Edgar Ben joseph will then talk about some of what we've learned in radiation oncology and how to best use that modality and innovations there in in the care of pancreatic cancer. Greg body is sort of the quintessential translational researcher. He is really the bench to bedside guy. He's going to talk about precision promise and the innovation in that trial design. That's really going to move the field forward. And I'm very happy that Michael Coachman could join us. He's going to lead off our question and answer session um, and explain to us some of the ways important, crucial ways that interventional gastroenterology interfaces with diagnosis and ongoing management of these complex patients. So perhaps if we could move towards in the interest of time towards Tricia slides um, and on route, I'm gonna show um, learning objectives. This is a CMI accredited talk in about one week, you're going to get an email that's going to tell you how to claim the credits and these are the relevant disclosures. And let me also say that in about a week, um, this content will be available in a webinar form and this will be an enduring program that can be seen over a year's time, several years. So that's going to be nice resource next Trish. Um, if we could transition to her slides and she can tell us Trish and let me just say, she really pioneered the role of nurse navigator, both at Penn and actually in the field. So um thank you Trish for joining us. Good morning. Uh Good morning everyone. I I it is such a privilege to be able to present everyone today. Um I am I have been navigating G. I. patients for the past 22 years of pen and the one thing that is quite evident to me that is one a patient is diagnosed with pancreatic cancer. It is a medical emergency for the patient. It's what am I going to do? I've just been told I have this terrible diagnosis and I know that pancreatic cancer is really one of the bad cancers, but I don't know where to start, who can help me. And during the course of the day I can get as many as five new patients calling me with a diagnosis and many are self referred. They hear a lot about pen and they want to know how can I get independent to be seen and get the best treatment possible. They're not sure if they should C. G. I. Doctor interventional, gastroenterologist, should they see medical oncologist, radiation, oncologist, the search of oncologists. And then for many of you in the audience who are physicians, you don't know, you know that pending has all these offerings but you're not quite sure um how you can get them access quickly if you can do the next slide terror. Um You you have just gotten a patient had been head called and said that uh they haven't been feeling well. They came to see their primary care physician and the primary care physician gets the imaging and imaging demonstrates the patient has a lesion on their pancreas. So I'll get a call from a primary care physician saying you know, Trish um I have to call the patient now with the results and I would like to have a plan where can we start? So that is the role the role of a nurse navigator at Penn. We're very fortunate in that. We have currently nine nurse navigators that are dedicated to different entities. Um I have a colleague colleague, I have a colleague who helps with G. I. Uh navigation and that's Diane Boyd but my focus is on pancreas cancer next life. Um We get referrals. All the nurse navigators at penn get referrals from many, many sources. We get them from, internally from other doctors. We get them from many family members who work at Penn. They have been diagnosed with pancreas cancer. We get them from patients themselves and from outside physicians which we encouraged to call us so that we can try to help next life. Um But for me, I think the most important thing is when I have a patient Comey for first time, it's really a bunch of we really have to triage, we have to know. Um Tell me a little bit about your story. Do you have a tissue diagnosis? Have you had any scans? Um What types of symptoms are experienced right now? And that tells me a lot, Like if they um I'll ask them, do you, what is your urine dark? Um Because then I'll know like, do you know if if you're what you're building when the level is, Because then I know that they really have to see interventional G. I. Um And what type of symptoms are you experiencing if they're in pain? I really have to get them in fast. Um Are you already on chemo many times the calls come and they'll say, oh I've been on chemo. And this is more fourth line of chemo. And there, you know, and you can tell that that they really need to see medical oncology. Um And then I also ask if they're interested in a clinical trial. Um as uh Arson has mentioned, there's many innovative therapies that we have at penn. And what good are these therapies if we can't get them in to see the right person at the right time? Next, next. Yeah. Um And then multi uh would I really like the stresses that pancreatic cancer is really multidisciplinary. Do you know what pen? We have so many tumor boards that are dedicated to a specific gi cancer. We have the um gastroesophageal, we have the liver tumor board, there is a colorectal tumor board, There's the generalist tumor board that we have every Wednesday. And then there's also um the neuroendocrine tumor board for pancreatic neuroendocrine tumors. And these, as Rosina has mentioned, these are very very helpful in deciding what is the best path for the patient going forward. But for the patient because it is multidisciplinary. They get confused as to who's on first. Basically they get confused as to does everybody know what's going on with me. And actually with the advent of the medical records, I'm able to go into their charts and say, well you know you talk to uh you sold doctor Coachman yesterday and dr coaching did your US and um we don't have the biopsy yet back. But as soon as we're going to get you seen by a medical oncologist or if I know that they've had a liver biopsy, I know that they don't need to see the surgeon, but I feel that we as a team, we really try to coordinate and get patients the right place at the right time in the trajectory of their disease next side. And as I said, a lot of times they just feel that it's their very confused as who, who am I supposed to see first? Who am I supposed to tell about? This symptom And as a nurse navigator, I think just put spending time with them and going through um, what their symptoms are unable to expedite their care. And also, um, I encourage anybody who has any questions. Uh, any Yesterday I received a call from a primary care doctor who really wanted to get their patient and soon and we're going to have them have their US. And it can happen within a few days. But I just want to stress that as navigators. it's important that we triage and get them to the correct person and that their care is expedited so they can be addressed. Thank you, Trish. And just to let everybody know this information, these slides will be available in about a week. As you can tell, Tricia's contact information is very important. As we transition to Dr Lee's talk, I just want to bring up again that we have a dedicated pancreatic biliary conference now and we often spend 15 or 20 minutes discussing a case pathology, imaging and sequencing. And Kenneth is going to speak a little bit now to some of the decision making that goes with a new diagnosis of pancreatic cancer, particularly locally advanced. Uh Mhm. Thanks for seeing. I'm gonna share my screen. Um Let's make sure this pops up. Okay, so yes, I'm in the division of Gi surgery here with an emphasis on pancreatic surgery and uh pancreatic cancer in particular. And uh when I try to do with this talk is kind of provide a couple of different things. One is just our perspective on patients who have pancreatic cancer. And then um you know, a couple of things that have come to the forefront in the last 5 to 10 years, I try to stay away from things that are too technical or a lot of pictures because I thought maybe that wasn't the best for this forum, but uh I'll keep it a little bit more general. So if a patient sees me first, uh and their newly diagnosed, there are a few questions that tend to come up almost every time. One is what is my stage second is can you remove this? And then the third is some variation of I need to know about a whipple procedure And you know, having done this a host of times, you know these things are coming and so I can kind of preempt them and uh and have the patients take a step back and I can tell them, you know, um you're just diagnosed. You don't have a stage, but rather we put you into one of four categories. And so the categories are one is metastatic, meaning the tumor has spread elsewhere and most patients don't see me. But some of them do. Um The other end of the spectrum is that the tumor is respectable, which means it's it is a relative chip shot to remove. And then the middle ground are patients who are borderline, respectable or locally advanced, which means that the tumor hasn't spread elsewhere, but it's wrapped around blood vessels in a way that makes it difficult if not impossible to remove. And so the we put them into these categories because it helps us determine what to do. The metastatic people get systemic therapy, chemotherapy to start almost always the middle ground borderline or locally advanced chemotherapy to start, there may be a role for radiation. And then some of them get surgery down the line. And then that kind of leaves us with the respectable people whose tumors look removable. And they're actually the most complicated group because they have, uh, the most options available to them. So historically, forever, uh, what we did with these people is we just operated on them and then our intent was to give them chemotherapy on the back end. And, you know, the the obvious problem with that approach is that the only thing that they're guaranteed is an operation. And then it all unfolds from there. And anybody who's taken care of this disease a lot has seen the following scenario play out, which is that the operation happens. The surgeon says, I got all the tumor out. The surgeons happy. The patients happy. Everybody's happy until they get their first scan three months later and they have either a cities or liver metastases. And then that turns into the patient is demoralized number one. They're stunned. And uh it kind of becomes well, you know, I don't know if I want anything else. And the same patient who was doing well five months ago is no longer alive five months later with metastatic disease. And so if you see that play out a handful of times, you kind of think to yourself, why is there a better way? And so that has kind of led momentum to multiple approaches. And now these patients have multiple avenues available to them. Some of them still get surgery followed by chemotherapy, Some can get, you know, you'll give neo adjuvant therapy, chemotherapy or radiation prior to surgery and then uh possibly a german therapy on the back end. And then there's the last option which is a clinical trial. And so I'm not gonna talk that much about trials because other people will talk about it except to say that for a disease with outcomes as historically poor as this disease. You know, we should be talking to patients about trials, we should be trying to put patients on trials because it's our way to make progress. Uh So most patients are gonna fall into one of these two paradigms surgery first, or Neo Ajman first. And it comes down to sort of the pros and cons of putting a patient on Neo adjuvant therapy. So why do neo adjuvant therapy first? And there are a few things. One is that it guarantees multimodal therapy. So you know, we know the patients that do best with this disease. Get surgery plus chemotherapy and the in the way to guarantee that for most patients is to give them some chemotherapy on the front end before you operate. Uh The second thing is it reduces futile surgery like the patient I described earlier five months later, no longer alive with metastatic disease. Uh Third is improved local regional outcomes like better margin status, better lymph node status. And I think um if you convened a giant panel of pancreatic surgeons, everybody would agree that these things are kind of fact like these are definite pros to neo adjuvant therapy. The question is whether it makes people live longer, like is there a survival benefit? And uh you know um there have only actually been a couple of high quality multi institutional trials that try to answer that question to this point, which is one of the problems. So one is called Priya Pink, which was a dutch study. Um It was based on old chemotherapy Jim cited being alone plus radiation versus upfront surgery and it showed no difference in overall survival. But again, this is a regimen that we would never use nowadays for a fit patient Jim sight of being alone. The second study, which is, I think concluded but not published, was a japanese study called Prep 02 which is a better chemo regimen. Jim S one uh which s one is an agent that use uh more commonly in Asia, but that versus upfront surgery and that did show a significant difference in overall survival um with a more modern chemotherapy regimen. And there are more trials forthcoming for fear knocks based trials that use modern chemotherapy. And I suspect that the fallout is going to be that there's a survival benefit on the side of Neo adjuvant therapy. So the question becomes, well, why not do Neo Adjuvant therapy? It's it's probably not for everybody. So who shouldn't get it or why should they not get it? And uh you know, there are few things that we run into. One is a lack of diagnosis, like some patients get two and three biopsies and you cannot prove the diagnosis. So there's reluctance to get chemotherapy upfront. Second thing is frailty, that's a real issue. Like what if a patient cannot get the best chemotherapy, does it become diminishing returns? Um So that occasionally comes up. There's some patients who present with obstructive issues, bio doug duodenum where they almost need an operation because they can't get chemotherapy due to all the local complications. Uh that certainly comes up. And then the fourth thing is this whole idea of, well, what if I miss my chance, which is a thing that the patients are constantly focused on. And a lot of providers are focused on as well. And You know, I could, I think that's more of a theoretical risk than a real risk. I mean, again, there's only been one trial, which was, I think, but in that study, 89 of the people who went on chemo with the intent to get surgery did get surgery. So I think that's more of a theoretical issue than a practical issue. But it is something that comes, you have to address with the patients. Um So I think, you know what shifted in terms of the preoperative approach with a patient with newly diagnosed pancreas cancers. We used to say, you go see a surgeon with a new diagnosis and they say, okay, well let me tell you about me and let me tell you how great I am at this. And let me tell you about whipple procedures. But that's all dead. I mean it's we don't function in a silo. Uh we kind of can't talk like that anymore. So we have to say, uh let's talk about your situation, let's talk about this disease. And and let's come up with a comprehensive plan and that's the way we have to approach it. So, um, you know now for a couple of technical things that have kind of changed over the last few years, um you know what hasn't changed for pancreas surgery is the operations, there are really only three operations that we do. Uh One is for tumors in the head of the pancreas. They get a whipple procedure. The other tumors in the tail of the pancreas or body. You get a distal pancreas checked on me. And then tumors that somehow spanned both can get a total pancreas attacked me. And the split point is really this vein, the superior Mezza Terek vein, tumors to the right, get a whipple tumors to the left, get a distal and tumors that kind of span both get a total. And so this is the relative proportion of what we do for cancer at least. This is national, not just here, but about three quarters of operations. We do our whipple procedures And then uh close to 20 or dissed als. And a smattering of totals. The issue with pistols is that most of these tumors metastasize before we can operate on them. So it's always gonna be kinda heavily, heavily oriented toward Whipple's. And so I thought um for each of the two operations we do at least uh tell you something that's come up in the last five years or so that I think is relevant. So for distal is this is a simpler operation than a whipple procedure. And yet, you know, historically, when we operated on these people we would inflict these massive incisions on them. And so even though it's a simpler operation and there was less to do, this is a lot to recover from. And uh so now because this operation is well suited to it, we can do these a lot of these laparoscopically. So instead of this, you know, this patient on the left is about three weeks out from surgery. And the patient on the right is probably about two months out from surgery. And uh what we do on the inside is the same. But this is obviously a lot less for a patient to recover from and I can get them onto whatever else they have to do more easily. So this is kind of here to stay. Um, this is just for me, like my own practice five years ago to now. Uh, you know, five years ago, about two thirds of these that did were open. Now, probably 60%. I do our our laproscopic, which again is a lot easier to deal with on the, on the back end. And so I think that's kind of here to stay in a big advantage for patients for distal pancreas tech. To me. Uh, now for whipple procedure is there are a lot of things you could talk about. But the one thing I want to talk about was the approach to locally advanced tumors kind of from beginning to end and and what we can do with these surgically because that's something that is also here to stay and and has changed a lot in the last five years. And so I thought what I would do is kind of show this one case, which I think brings together all the concepts that I've been talking about. And so this is a 45 year old Who presented with jaundice and weight loss. And he was diagnosed with cancer here on in February 2019 and that time, this is a bad tumor. The tumor is all centered here. But the key is that his superior Mesen Terek artery, which he needs is surrounded by tumor. The Superior Military vein should be here. It's gone. It's completely obliterated by tumor. And so he gets a cat scan report that says he has a four centimeter tumor which surrounds his superior Mezza Terek artery and causes complete occlusion of his portal vein in a splitting vein. And actually saw him at this point up and he was an inpatient. He had been admitted. He's got four kids kind of running around the floor. And I told him a few things. I told him, um you know, I told him You are treatable. Um I do not know whether you are operable. You know, I told him you should not anchor yourself to the idea that surgery is the only way to deal with this disease. But we're gonna put you on chemotherapy and we are going to see what happens down the line. And this is what happened. He was diagnosed, he got 12 cycles of full fare knocks he got, which is standard chemo. He got a standard dose of radiation from october to november. And he came back to see me as a year later. And uh I had seen his scans multiple points along the way. He had a whole team here. But again, I did not see him physically for a year. And when he came back to see me as tumor was about half the size. He had a lot of vein involvement. Still he had haze around his celiac. He had haze around his sm. A but you know with his age and the fact that he had normalized this tumor marker, we said, you know, we're gonna operate on this and see if we can extricate it. And so this is what we're gonna do. This is like an extended whipple procedure with the vein resection and a reconstruction. And basically normally when we do a whipple, we divide the pancreas over this vein and kind of take the pancreas off the vessels. But in this case we sort of divide over to the left and work back and take out the tumor with the vein kind of attached to it. And so that's the approach. And I do this with Ben. Jackson is very talented vascular surgeon when you have to put these things back together in a complicated way and we do them all together. Um I always do them with Ben. He knows about him ahead of time and we always worked together and I'm not the greatest uh interact photographer. I just don't have the bandwidth. But this is the this is what it looks like. This is the patient's vein up here. The patient's vein down here, there's a big segment gone. The pancreas is gone. We replaced with a piece of categoric aorta. His S. M. A. Is over here and you know this patient, this was his path report. He had small focus of tumor, a near complete treatment response. All his margins were fine. All these lymph nodes are fine which is the best outcome that we could hope for. And uh you know I picked the case for a couple of reasons. Um The first thing to say about this patient is what happened to him is not some kind of like one in 1000 response to some unique therapy. I mean this is all standard stuff like he got standard chemo, he got a standard dose of radiation and he got an operation which is not the most complicated thing that we do and it's not some newfangled operative concept. But um you know it's not an easy operation but we can do it. And the key is that he got all these therapies that kinda helped along the way. And the second thing to say is that, you know, to the surgeon goes a lot of the credit a lot of times. But you know, this guy had a team from the beginning from beginning to end. You know, he was diagnosed here by Greg Ginsburg who had to manage his biliary tree throughout this. You know, Jenn and Katie from oncology and Andres and Aaron from radiation and then, you know, he gets an operation on the back end and so, um, I did not see him for a year, but he had a whole team that was involved the whole time and we all talked about him multiple times along the way. And this is the type of thing that we need to kind of deal with these patients, especially locally advanced tumors and to try to make progress with this disease. And so I think, um, you know, the summary is, we're making progress with this disease. I think all the patients have to be treated comprehensively. Nobody functions in a silo anymore. I think any patient who has a locally advanced tumour, not metastatic, has to be evaluated for surgery because what we can do now is different than what we could do in the past. And you know, they're not all surgical, they don't even all need to physically see a surgeon, but all their films need to be looked at because there are a lot of patients out there that are probably told that they're inoperable that actually are and they would never know. And um, we just have to do it all together to take the best care of our patients. And uh, I think that's uh, it for me. And I'm happy to take questions at the end. I'll turn it back over to thank you Kenneth. And as we transition to kIM rice vendors slides and she's going to talk about what is a great word again, curative approaches from a medical oncology perspective. I just want to say that even though the therapies were standard full fare knocks, these are only been really standard care for the past 10 years. The pace of innovation has been terrific and kIM and the key is clinical trials. And also again, this multidisciplinary approach, can we load kim rice bender slides up please. And we're going to let her speak to some of the Trial innovation in the in the curative approach setting. And I just want to say also, you know, borderline respectable is really a term that is now possible due to meaningful chemotherapy combinations and we didn't, you know, as of 2011 we had one option genocide of being alone and now we have multiple kim. I think you are. Yeah, thank you. I before I start I'm going to talk some of the talk has some overlap with ken's talk. But I first want to say actually that it's one of the great joys of this job is actually this multidisciplinary group approach. We do indeed truly talk to each other about every locally advanced patient, every respectable, every borderline, respectable case. And and there are multiple times along the treatment where we communicate with each other. And I think patients feel that I think they feel that we're actually in sync. Um they feel that we all like each other truly like each other, get along and try to communicate with each other very, very frequently. So it's one of the things that I think is a benefit um for a great benefit to have that expertise here on multiple different fronts surgery, radiation, and medical oncology, and then in addition, the things that Trish mentioned, genetics and nutrition and um social work and you know, all the other options for patients. So very quickly I know that there is a kind of a broad group of patients on this. Sorry, a broad group of people on this call today. So I wanted to very quickly review some of the signs and symptoms of pancreatic cancer that that sometimes go missed often not. But things that just might make you think that maybe an evaluation is necessary for pancreatic cancer. And one of the difficulties with this disease is that many of the symptoms are relatively vague and could be explained by other things. So abdominal pain or back pain is an extremely common uh sign or symptom and could be explained by a number of different problems, um loss of appetite belching or at least early satiety. Um And then there are a couple of things that actually are more specific and sometimes go go unnoticed. And so those are the things that I wanted to bring your attention to. So one relatively common finding is people with worsening diabetes or a new diabetic diagnosis. So often there's somebody with diabetes already who suddenly has a big jump in their a one seed without waking without changing medication without dietary changes. And so that's kind of turned the antennas around about what might be causing that issue. And in fact I've seen a number of patients over the years who were sent to us by their under criminologist because that person noticed that there was a change that was not otherwise explained. Um fatigue obviously very vague but stay out of real, which is oily, oily stool and is explained by the fact that the pancreas is not functioning well and is not able to assist in the digestion of fatty foods. That's a very common um finding for us and then as Trish mentioned uh signs of jaundice and and and a biliary obstruction. So john disclosure, electricity, colleague stools and dark urine next life. So the diagnostic evaluation of this disease is one that we usually undertake here. That's not one that gets done in the primary care setting usually. Um, but the first things that that are helpful to us are some basic labs and obviously imaging studies. Um cross sectional imaging is preferred cT or MRI um There is a very limited role for pet scan and pancreatic cancer. And I just wanted to make that point because they're often used and they're probably not necessary for most patients. And in fact, 10 to 15% of our patients will have a negative pet, even in the setting of this tumor. So it's it's something that people often ask about and patients will ask you about. Should I get a pet? Can I get a pet? And the answer is it's probably not helpful. There are some situations where it is helpful but it really should be a very limited use. And then brain imaging, which is often done in other tumors at staging. It's not required for this disease because of its lack of uh lack of frequently doesn't go to the brain. It does, but it often is not a diagnosis typically. Um Then the pathological confirmation and this is usually performed by one of our gi doctors. Dr Coachman Dr Ginsburg dr Ahmad, usually one of the doctor lee one of them differently. Not Kenley. Um We'll do a biopsy G. D. U. S. And then a biopsy of metastatic disease if that is applicable. And one final point that's really changed in the last couple of years since I have joined the faculty here is that all patients with pancreas cancer should get genetic testing with once they've had a confirmed diagnosis and that's both for their family but also potentially to guide their own treatment. Um And it's known now that 5 to 8% of people will have a genetic reason for their pancreas cancer and that if we only test based on clinical suspicion like they have a strong family history for example, we will miss people who have an alteration if you have a person in your primary care doctor whose first degree relative had pancreas cancer and was not tested. There's now indication for those people to all undergo testing. Excellent. So I will um you know, I will actually skip this because can do the exact the exact same thing. And again, we're kind of all together on this. And then this is again, also what ken was talking about will make a couple of kind of additional um points patients used to be treated with reception and then add different chemotherapy. And now we sometimes place surgical resection in the middle as a sandwich. Or do we do the chemotherapy a stick in the case where um where can present it? Although that was a locally advanced case. We give should we give the chemotherapy all up front And these are kind of nuanced decisions because some patients will say I just wanted out. Um or there's a reason like frailty as can mentioned that that they may want to take them to the operating room at front and then try to do chemo in the back end. But for a lot of patients, for the reasons that can mentioned, we want to give some portion of neo adjuvant therapy or do we want or we want to give all of it neo adamantly. And that's a decision that gets made um Together with a surgeon with the radio operation on radiation oncologist, with the medical oncologist and with the patient, about how much of that chemotherapy do we want to give? Neo adamantly? And how much do we want to kind of save for the back end? I'll say that it's a lot easier to give people chemotherapy typically prior to, especially if they're going to get a whipple because after a whipple there's a lot, there are frequently more digestive issues. Um And so given drugs like Phil Fearon Ox, which can cause diarrhea, constipation, nausea, vomiting are more difficult to give in somebody who maybe has no nutritional or digestive issues from surgery. Um But on the other side you don't want to give, you don't want to blast somebody with chemotherapy to the point where you bring them back to ken and he says absolutely I cannot take this person to the O. R. Now. You you've wrecked them. So we try to find kind of the middle ground and I usually tell patients look if we're going to do the the neo adjuvant approach and we're talking here just about respectable patients. Um But also I guess you had to uh locally advanced and borderline er is applicable as well. We're going to do this two months and two months at a time. Our first benchmark is two months into your therapy. We're going to give you four doses, we're going to re stage, we're going to reassess and we're reassessing your clinical status. How are you doing on the chemo? What's your weight? What's your nutritional status and what are your scans look like? And so we kind of inch along an inch along and make the decisions as we go. And then after surgery, whatever is left of a six month period of chemotherapy can be given on the back end potentially if the patient is still able to receive that next slide. So as as we've been talking about the outcomes for these patients are not as good as we want them to be even in the respectable setting. The The trial that has established Filthier Knox as the gold standard for chemotherapy in the Peri operative setting or adjuvant setting, meaning the curative intent setting um gives you an overall survival, median overall survival of just over four years, which is good. But 50 I think actually 54 of patients on that trial still Rickard. So what does that tell you? We're still not with the best care that we have, we're still missing. Half of our patients were not curing half the patients. So this is a trial that's going on at penn Tom. Karasik is the p of this trial. It was kind enough to give me the schema and don't look too hard at. It makes me, makes me kind of busy looking at it. But basically what we're trying to do here is make the neo adjuvant therapy better. We're trying to get more patients to cure and I'm not I'm not going to talk about your trial because it's a locally advanced uh Berlin respectable trial. I'm only focusing on respectable here and that's the reason that the slide that's up. But this basically is trying to add uh immunotherapy and vitamin D. Intravenous vitamin D. To a really strong chemotherapy regimen for respectable patients before they go to the operating room. And what we're trying to do is we're trying to, first of all, we kind of learned because if you then take them to the O. R. You can look at their tissue and see what you've done with your therapy, which is really important for us as well. Continue to design future trials. But we're also trying to reduce the surgical um, you know, the surgical field shrink the tumor, reduced margin, positivity, reduce lymph nodes and we'll see how this all this works over time next week. So surgical reception on its own, we know is not curative for this disease. And the vast majority of patients. And that's a really important point because patients will come in and they're very focused on their surgery if they're recessed. And again, I'm talking about respectable patients are very focused on get it out. And the problem is that, that doing that alone is not, is not curative by itself. This is a systemic disease typically already at diagnosis, even if you can't see that. Um, so the goals of our chemotherapy are to eliminate that micro metastatic disease that we can't see, render the tumor operable and also prevent the local and metastatic recurrence risk or reduce that risk. And these are the regiments that have been studied over the years. As I mentioned, the produce trial, which is that third study, their established really kind of blew every other study out of the water. Um, and established full fear knocks which patients will know and if they've read about it, it is a difficult regimen. It's a tough thing to get through. Um and it's been established as the standard of care. One of the things that we'll struggle within medical oncology clinic is patients who are frail and patients who can't get full fear Knox. And the question is, what do you do with those people? And nobody really has a great answer to that. Um There are a number of other regiments as you can see there that may be less toxic, but um but that's a situation that is that is unfortunately not infrequent. You know, you've had surgery, you're going to have surgery um but you're not really fit enough to get full fear and how should we treat you? And that's something that we also talk about. It are multidisciplinary conference and obviously curbside each other on frequently on how to approach those people. Excellent. Um this all skip. This is just the showing the produce trial. Is that is that that it was good. Okay look at this lady this is not my patient. I found her on the internet but I think she is awesome. This is what I'm going with her five if you pump. Um So what is full fare knocks mean to patients? So what will you what? County council somebody Very very briefly it's given every two weeks. It's an infusion. It is required that support that you need for this particular infusion patients come to the clinic every two weeks they get an infusion over about four hours of the drugs and then also of supportive drugs. So they will get into their infusion, anti nausea medications, steroids, a couple other supportive things that go in with their infusion and then they go home um With this little pumps that you can see this woman is holding and that runs for two full days at home. One of the best things that pen is the pendulum infusion um contract that we have with the pendulum infusion team at the end of that two days that those people will go out to that patients house and unhook them so they do not actually have to come back to us to get that pump and huts and where I trained they have to come back. So I really appreciate the fact the patients only have to travel to us once every two weeks. The common side effects are there? Um The one that I just want to highlight is the cumulative peripheral neuropathy. So as you might imagine we have a generally older population although unfortunately it seems to be moving younger. Um But we generally treat people in their sixties to seventies to eighties that would say most frequently. And if you have um, oxalate platon causes progressive tingling, a numbness of the hands and the feet. So you have to, as a medical oncologist, you're trying to get that person six months of this drug. They're almost guaranteed that they're going to have some neuropathy. And so you have to be incredibly mindful of monitoring that over the course of their care because if you're not careful, you can put somebody in a position where they can't live independently or they can't do the things that are meaningful to them. Um, if you have a patient who is a musician, an artist, a surgeon, um you have to be extra careful and there are some things that we've studied here to try to mitigate um to mitigate that next time. So what we did a couple of years ago, this was actually the way that this evolved is that you're seeing it and I was sitting next to each other at ASco and if you remember this and somebody was talking about on the podium, talking about neuropathy and arsenal turned to me and she said we should try to do something about this. Why don't we do a study where we uh where we uh try to reduce the, reduce this peripheral neuropathy. And the other thing that we wanted to try to reduce is something called cold sensitivity, which is not the same as neuropathy, it is not cumulative and not permanent. But when patients get oxalate platon, in addition to this numbness and tingling, they will have an experience of um any time they touch something cold and with their mouth, their throat, their hands and their feet, they get a very strange sensation that's described often by patients as shards of glass in their mouth. And so, um, we did a study here again, based on this discussion I had with arsenal where we had patients actually stuck on ice cubes during the rock solid platinum fusion and actually found that indeed, it greatly reduced their uh, their experience of having this strange shards of glass sensation which opened the door for them to eat things like ice cream and cold things um, after their infusion again, trying to, you know, hope in the hopes that would balance out their nutrition and improve their quality of life. The oxalate platinum apathy is actually the same thing. The, the permanent neuropathy can also be reduced by applying ice to the hands and feet. And it's actually incredibly simple. You're just causing local vessel constriction wherever you're applying ice. That area gets less chemotherapy exposure and therefore you have less of a less of the symptom experience. So those are things that we counsel our patients on. And I have a patient to patient. Yesterday came in with a whole Like a camping cooler full of ice in preparation for doing this during her for, you know, during her 120 minute infusion. It's hard for patients that they give their motivated, they can do it. We have a number of things that can help with neuropathy. And we also have a actually a pm and our physician who is as an expertise in the treatment of neuropathy. And so that's a wonderful tool to use in patients where we Um where we feel we're kind of at the end of what we're able to offer in terms of making that better. But that is a big quality of life and functional issue for patients after getting 12 cycles of full fear. Not. Yeah, so one more quick um I think this is the last slide. So we, again I mentioned every patient should get genetic testing. Um uh in the metastatic setting there is a drug called elaborate which is targeted to these patients. So if a patient has a has a mutation in B. R. C. A. And Baraka which is commonly thought of as a breast and ovarian cancer gene but actually carries a risk for pancreas cancer as well, patients can actually get this in the metastatic setting with a benefit. And so we are now trying to see if we can do that same thing and move this into the curative intent setting. So for patients who have a genetic testing and are found to have such a mutation have gotten all their standard of care curative intent reception. Um Chemo radiation at whatever the the local team decides is appropriate for that patient. That patient with an ordinarily go into observation. We would ordinarily be checking scans every few months saying that patient, but no further therapy would be offered and instead we're going to offer them a one year trial of elaborate this pill versus a placebo pill and it's randomized in 2 to 1. So for every two patients that get the drug, one patient will get a placebo pill and of course that will be blended. So that trial was born here Um and we'll open nationally and actually internationally at up to 600 sites. Next this month is April yeah, this month with us leading that and the hope is that this improves that 50 and you know in these patients that improves the curate in this select group of patients. Um very recently I'm done breast cancer trial with exactly the same design was recently reported as for patients with BRC related breast cancer. So we have high hopes that this will be helping our patients. Um and we'll have some good results in a couple of years. Thank you kim. Um And I'm just going to ask that we transition to Dr Ben joseph slides um two points where about 10 minutes behind. So as the next two presenters are speaking just to keep that in mind. I really want to dedicate at least five minutes at the end, particularly since we have several questions for DR Coachman. And also to tim's point this is usually a disease of um aging. So frailty is a really important consideration and robert. The can be really limiting for these older patients that you want to prevent falls in and get to the O. R. Safely. So those are those two points Dr Ben joseph, Vice chair for Clinical Research and radiation oncology and really our expert trialist in this setting. Thank you. Edgar Dr Ben joseph. I think you're muted. Okay. Can you hear me now? Yes. Great. Okay. Sorry. Okay. So let's jump right into that. We're going to talk this morning about advances in radiotherapy. And I want to start with the end the summary uh you know, radiotherapy is a local modality um treatment type and we address local disease. We cannot address metastatic disease. Um And pancreatic cancer has been said is a systemic disease and the majority of cases at presentation. So the expectation that radiotherapy would improve survive on has always been a little bit funny. Um And today we have a lot of evidence and to me the totality of that evidence is that radiotherapy does not improve survival in this disease. At least not in the way things are today. Um and really no chance for it to improve survival because the majority of patients present with micro metastatic disease. So what we really need to focus on and have focused on the past few years as to how to make it better, make it better local control modality to prevent some of the complications that go along with local relapse of local um progression. And how can we select patients for radiotherapy in a way that is going to be more meaningful. And I want to say at the end, just a few words about smud for as a tool, molecular tool to select patients for local therapy. Um I'm gonna review some of the technological promises um that allow us today to deliver high radiation doses that are more effective with more precision and with less toxicity. I'm going to be touching on carbon iron therapy. EMR guided adaptive therapy. And I also want to dispel some myths in the, in the field that are propagated. Um, and particularly um the claims about standard dose to tackle body radiotherapy, which I think is actually inferior form of radiotherapy in this disease. Okay. I'm not going to talk about all the trials in un respectable disease. You can take a look at the table yourself, but to me this speaks pretty clearly to the fact that there's no demonstrable advantage in survival to radiotherapy. On the other hand, we have made a lot of progress in the last couple of decades. We improve the local control twofold actually. So it's two years the local progression of failure had gone down for about two thirds of patients to roughly one third of patients with the treatments we have in today. Uh, I want to say that local failure is symptomatic and from the data that was published by Nobody down here from Hopkins about a decade ago, We now know that it leads to death. Local complications lead to death in about 30 of patients. These are the 30 of patients on whom we can make a big difference. And finally, that the standard of care, the therapy there's today is grossly inadequate. It's limited by radiation sensitivity, normal structures in the upper abdomen. And we are addressing this thing right now with a clinical trial at expense. Next line. So among those technological advances, I want to talk briefly about treating patients and breath hold or getting about target volume reduction. So there's a clear coalition between complications of 30, with radio 30 and the volume of tissue that you radiate in the ambulance. Um, products, we have looked at that. There is no clear benefit from products in this disease. But on the horizon we have carbon ions which are similar to protons but heavier in weight and carry much more of an impact. We can talk a little bit about adaptive 30 on the marlin axe and then talk a little bit about what is not promising but is heavily hyped by other institution, which is standard those protective body with next line. Uh These are two graphs from two clinical trials that I've ran previously um about 10, 15 years ago. Um two different regiments on the left is concurrent full those jump side of in radiotherapy. And on the right, it's just uh genocide of an exotic latin and registered people given together as neo adjuvant therapies or as uh as definitive treatment for unrestricted and disease. And you can see that there's a clear correlation between the volume that P. T. V. Stands for planning target volumes and the volume that you irradiate and the severity of jihad existed. These plots Grade 3 4 Gi toxicity, so how to make the volume smaller by treating patients at battle. Next slide, there are a number of different devices we use, for instance the one on the left at penn. But you can treat patients with breath hold and then you can take the volumes much smaller because the pancreas moves. And we have described that also about 15 years ago. If you make the pancreas stand steel and treated breath hold, you can make the volumes much smaller, include far less investing in your radiation fields. Next I want to speak a few words about still attractive body radiotherapy and why this is not a good treatment for pancreatic cancer. The two panels on the left show you a classical, un respectable patients that we see coming into the clinic every day in the sort of greenish color where the arrow points. That is the do afternoon. And once you apply to your target, the expansions that we typically apply for motion for the formation for setup errors. You see that a the majority of these patients that target overlaps with duodenal. And if you try to deliver and a bladed radiation, those to that volume, you will oblate a portion of the duodenum, which is not good. On the right hand side. You see a classical case of still attacking, by the way therapy. These are smaller tumors that are away from the intestine. The arrow points to contrast in the duodenum, you can see that there's a good distance between the target, the small target that is being treated here and the do afternoon next line. So if you look at standard those radiotherapy, there's a number of different trials and publications uh, and you can see that the data does not actually support that there is a benefit with the attractive body with the survivals are roughly the same as what you would get with external beam radiotherapy. Um, but these patients that received the attacking, by the way therapy are highly selective. They have smaller tumors. They are away from the intestine and need to atoms in a sense, they are the easiest patients to treat with the smallest humans. And they only represent really at most 10-20 of the patients within respectable cancers. Um, um, and they also have been treated and sort of later in time. So they are better selected in terms of stage migration. They have been often stayed with them are or with a pet. Uh, and the probability that a harbormaster study disease far smaller. So in my mind, data pretty clearly suggests that's the attacking by the red therapy Has nothing to offer to patients with pancreatic cancer except for convenience. You do this in five fractions rather than in 25 fractions. Uh Next slide well, uh a very interesting and promising technology on the horizon is this magnetic resonance guided radiotherapy. And briefly what that is. We now have machines that have em are installed into the linear accelerator. And you could actually um our patients just before they get their treatment on the treatment machine, see where the stomach intestine and water. Nomar because you can see them far better on NMR and then adapt your therapy immediately before you give it. And indeed the papers that are starting to come out show that the complication rate had dropped quite dramatically. Um You can see in this particular paper Which is a consortium of five different institutions, the severe toxicity dropped to zero uh you know, there's another a few other patient but we we don't really have much time. So you can read the slides like that your leisure, let's skip to the next line. Carbon irons is another very promising approach to this thing. They're similar to protons, but the those distributions are actually even better than than protons and they also carry a biological advantage. That is they are 3-5 times more effective than photons or protons. And the 1st Phase one has been reported by the Japanese. Uh And similarly to the M. R. Guide that shows a very dramatic drop in toxicity as well as a significant improvement in in control and maybe also in survival. I have to say, the University of Heidelberg has not been able to reproduce this data. But there are two phase studies right now internationally that are running one in Shanghai and one in Heidelberg. I'm going to skip this because dr lee had discussed respectable border, respectable disease interrupt because I really want to have uh DR coach men's expertise on, I have a couple of questions for him. I just wanted to say now that patients are living longer. The importance of local control is even greater because that's where they have a lot of symptoms. Um Michael, one of the big issues. We run into patient presents, jaundiced and we refer them to you. And not only do we need to address their biliary obstruction, but we have the need for biopsy, it's notoriously difficult to biopsy pancreatic cancers. And now as medical oncologists that are looking to enroll patients on trial, we want bigger, better biopsies as we patients read online, know your tur and we want to sequence everything and we have the opportunity to do so can you just address some of the innovation in uh in biopsy and also just management of locally advanced disease. Thanks er Sina and and great presentations from everybody. So the question of obtaining tissue is critical because it's a fiber optics trauma. And I would say that all of us on the interventional endoscopy side are able to uh perform endoscopic ultrasound guided biopsies. The issue that you're asking about is an attempt to get core tissue that can be used for both pathologic and molecular diagnostics. Um And that is possible with really any of the needles. The quote unquote fn a needles are somewhat helpful for that. But one of the key things that is born out in the literature starting about seven or eight years ago from japan is the use of saline suction. Um If you think about it, if we just apply suction, the gas attraction to the tip of the needle is not that great. But if we have a water column that we're trying and have negative pressure on that actually transmits the effect of negative force down to the tip and were able to get some nice core. So it takes really rapid strokes into the tumor to load the needle and then reviewing that with or without the on site site. A pathologist. There's No question that there is born throughout the literature. An additional 10 and up to potentially 2025 diagnostic sensitivity when there is on site pathology. But the real key issue is to make sure that your tissue sample is adequate. Um in those patients that have large necrotic tumors were really going to fail because often we get the really necrosis and we're not able to get viable tumor cells. Um, and I'll stop there if that answers that question for you, Anything else that you really want referring physicians to know? Um in terms of, you know, jOHN does not johN just when to see what you can offer a diagnosis and in the continuum of their care. Uh that's a great open ended question for which I have about two minutes. Um, so I would say the most critical thing is the patients that dr lee and I see upfront, meaning the gastroenterologist insurgency um are often extraordinarily anxious and have not been given, really. Um the perspective that we're trying to convey to the audience today, that the issue of chemotherapy prior to surgery is one that needs to be addressed. Because often the patients I see, I'll see them for the tissue acquisition. And then the next question is, how quickly can I have surgery? And I spend a fair amount of my time quickly educating them that surgery is something that is one of the tools, but really the most important tool to prolong survival is either the chemotherapy upfront or after surgery and that they need to be individually assessed for that, which I think is really critical. Um and I would hearken to add that. Not all of the patients that come with quote unquote pancreas masses have pancreatic cancer, especially adenocarcinoma. Often outside scans are not of high quality and pancreatic cystic nia plasm, which do not require surgery, are often misidentified or red as a pancreas cancer. In addition, there will be different approaches if it's a neuroendocrine tumor, if it is a sort of papillary nia plasm and it's really important for us to see these patients to potentially obtain tissue when appropriate. And I'll also Harkin that in this day and age. The big issue for gastroenterologists is the placement of the metal end of prosthetic and I would caution against that in the absence of the definitive diagnosis. Is I've been contacted numerous times for patients that may have autoimmune pancreatitis and which would be treated obviously with steroids um and not with chemotherapy. So it's really critical to differentiate that and I'll stop there for now. And Michael, it's incredibly helpful when you and inform the patient up front that surgery might not be the first thing that we do. But somewhere in the continuum having them come to us that way is much easier. If we could put up Dr Beattie's second slide, I do want him to have a quick moment to talk about precision promise which is a study um that is opening actually open now um um that we are one of the members of and it's a really unique trial platform that I think is really gonna help move forward the progress in this field. Um And um Gregory's part of he's a translational director of our pancreatic Cancer Research Center and really our bench to bedside lab to clinic guru. Thank you Gregory. Thanks martina. So I just want to make a couple points that You know, one of the challenges that we've had in the field is particularly for metastatic disease is the overall survival remained low around three for five years survival. And we need new ways in which to move strategies forward much quicker. And the idea behind this trial design that's sponsored by the Pancreatic Cancer Action Network is to set up a adaptive platform trial. Which means that therapies that are tested are constantly monitored to see which population of patients actually will benefit. That's the adaptive component to it. And the platform aspect allows for the integration of new investigational treatment strategies to be tested against controls, treatment arms, there's to control arms the full fare knocks and genocide of being a practicing uh in this trial. Um, and this allows for us to more seamlessly test them quicker to get results in patients. It requires fewer patients to see if there's a results uh that will be that's beneficial for a treatment arms. So only 100 and 75 patients need to be enrolled. Whereas most phase three trials, Well a crew 500 or more patients um for an arm to see a benefit and there's 232 If you go back to the previous, there's the previous. Yeah, that one. Um There's two components here that are that are that are also important is the incorporation of biomarker research. So every patient actually undergoes tissue biopsy so we can learn about the the patient's tumor as well as how and how it evolves over time in the face of treatments. This will help to inform new treatment strategies. And an important point of the trial is also the inclusion of supportive care. We want to monitor their daily activity using active graffiti. We want to be able to understand changes and weight loss using CT scans. Um and uh this all of this is conducted within a consortium. Um so there's at the moment 15 clinical trial sites around the United States that patients can go to. And this is really designed to be a trial in which patients are followed through their entire history of their disease. So patients can enroll at first at the first line of therapy um if they have metastatic disease and they can be re randomized to second line therapy um if they progress. Um And so a new approach that's open um here at Penn um for patients. Uh so it is a trial that um we are actively accruing. There's it's slots are always available, which is very nice about this particular clinical trial. Thank you. Gregory. And and on behalf of Penn Medicine and the Abramson Cancer Center, thank you so much for joining us so early this morning and for staying a few more minutes actually, I think what you're getting is that there is a lot of hope um and and progress we have um through collaborative efforts through multidisciplinary care. We're really moving forward the opportunity for curative approaches and also um prolonging patients lives and meaningful ways. One of the things I'll say to Edgar's point of slides, patients are living longer, so local control is becoming more important symptomatically and by really harnessing all of our tools, supportive care, nutrition, nurse navigation and all of the services of the Abramson Cancer Center were able to really make a difference in these patients lives. Thank you all for joining us. All of this information will be accessible online in about a week, including all of our contact. And we we like to hear about patients early enough and particularly if their trial opportunities for them. And you know the covid slowdown is opening up now. We actually have a lot of trials coming opening quickly for every line of therapy, preoperative postoperative and multiple lines in the metastatic setting. So thank you all for joining.
