Experts from Penn Medicine discuss and review the latest updates in thoracic oncology, including COVID-19 vaccine-related updates for immunocompromised patients and the manifestation of lung disease after COVID. Additionally, they cover impact of COVID on lung screenings and how to motivate patients to resume routine screenings to ensure accurate diagnostics. This multidisciplinary team also elaborates on novel treatments, clinical trials, and forecasting the future of treatment in medical oncology and radiation oncology.
Cancer and COVID-19 Vaccination | Penn Medicine Recent Advances in Oncology Impact of COVID-19 on Cancer Care | Penn Medicine Twitter @PennMDForum Dr. Aggarwal’s physician profile Dr. Kucharczuk’s physician profile Dr. Berman’s physician profile Dr. Haas’ physician profile Yeah, yeah. Mhm. Yeah. Okay. Yeah. Mhm. Oh! Oh, Mhm. Oh, we're gonna wait another minute or two to get started as people are signing on, so we'll probably get started about 12 03 Oh. Okay. Well, we're gonna get started. Um, good afternoon, everyone. Happy to invite you to spend an hour with us to talk about updates in thoracic oncology. Um, we have a great panel today. We have representatives from our interventional radiology, uh, interventional pulmonary department. Dr Haas, Medical Oncology. Dr Carew and radiation therapy. Um, Dr Abigail Berman. I'm John Karr. Chuck, I'm the chief of thoracic surgery at the University of Pennsylvania. And really, today's agenda is to talk to you a little bit about lung cancer screening and advanced diagnostics. Updated medical oncology for lung cancer are updates on treatments and radiation oncology as well as kind of an update on the current state of covid 19 vaccination. Obviously, our practice patterns have changed during the pandemic. Um, it has affected, um, not only are providers our patients, um, but has made us kind of change some of our protocols and some of the way, we approach patients with lung cancer, so We hope to share some of this with you today, uh, and give you some of our insight. What the over what the past year has brought us. Um, you can see here the learning objectives, and really, we want to focus on lung cancer and especially lung cancer. In the era of covid 19, this activity is designated for one category one credit. Um, and you can claim the credit. Importantly, the credit. You will receive an email from the University of Pennsylvania from the semi department within one week. Um, and it will give you instructions on how to fill it out and obtain your, um, cmi credit. As you can see, I do not have any disclosures. Some of our other faculty do have disclosures, but don't directly affect any of the, uh, talks or speeches that they'll be giving today. So thank you all for joining, and we'll go ahead and get started. Our first speaker is going to be Andrew Haas. Andrew is the head of our interventional pulmonary program. Um, he is really key in a lot of the first steps are patients take which is in diagnostic diagnosis and staging, and he's going to talk to you a little bit about lung cancer screening. What's the evolving status and a little bit about how the pandemic has affected the screening efforts? So, Andrew Thanks, John. Thank you all for joining us today during the middle of your day or busy days. Um, participate in this with us and I apologize. You have to look at my ramshackle background here, but the standard background was actually not working for the amount of light in my room. So, um, we had to get started over this Not too distracting. So I want to just start off by talking about what makes a good screening test as we think about lung cancer screening. Why would that make a good test? And as we design and think about screening test, they should be inexpensive. It should be easy to perform and safe. Shouldn't put the patient at risk should be minimal discomfort to the patient. You really important. We should be able to detect the disease at a pre clinical state where it's going to make a difference in health outcomes and mortality for the patients, and it has to be able to validly discriminate between disease versus other abnormalities that may seem in those screening tests and has to be widely available. This can only be available at certain centers. It's gonna be very challenging to implement that more broadly in a General Izabal fashion. Yeah, so why should we screen for lung cancer? Think as many of you know, there's really an epidemic and a scourge of lung cancer that really began about 20 to 30 years after the mass production of cigarettes. And so if we look at 2019, it's about 225,000 lung lung cancer diagnoses. And if you look at the deaths, there's about 140,000 deaths per year from lung cancer and in males. That's more deaths than the next three cancers combined, and in females, it's more deaths than the next two cancers combined. So this is a huge mortality that happens as a result of lung cancer and why there's benefit from screening If we look at the survival rates while they are definitely improving all comers, the five year survival rate is still only 15 to 20% and we're still very poor finding these patients with early stage. So most patients 15 to 20% or so are presenting with late stage disease, where they no longer on a curable state. And we very obviously we know the patients we need to screen as opposed to colonoscopy or mammograms, or it's a much broader population. We just need to screen patients that have a high risk from their prior smoking history. So the first I'm gonna go through two quick trials that looked at lung cancer screening. The first was the national Lung Screening trial. This was actually the largest trial ever funded by the NIH. It was a $250 million clinical trial that randomized 53,000 patients between standard chest X ray or low dose CT scan obtained annually for three years and then following those patients for 10 years, patients were 55 to 74 years of age, had smoked at least 30 pack years and were either current smokers or had stopped smoking within the last 15 years. They excluded if the patients had a prior history of cancer, if they had a CT scan done in the prior 18 months, or if they have evidence of potential underlying lung cancer. they had homeostasis or unexplained weight loss. If we look at the results of the N S L T, there basically was a 20% mortality reduction from lung cancer specific death. Interesting that there was an all cause mortality of about 16%. I'm sorry. About 6.7% as a result of finding other unexpected findings such as coronary artery disease, corny calcifications, renal lesions and so on. So they can all cause mortality benefit as well. And interestingly, is we would have hoped and expected low dose screening detected many more stage one lung cancer. So there are 400 stage one lung cancers in the low dose screening trial. I'm sorry in the CT scan, as opposed to only 100 and 30 in the chest X ray. The downside is you see a lot of false positives. So up to a 3rd 20 to 30 25 to 30% of patients will actually have a lung nodule, with the vast majority of which will not the lung cancer and that need to be followed prospectively. And then you need to decide of those modules. Which one you're going to biopsy, recognizing biopsy in the lung is not necessarily easy to do and comes with potential risks of morbidity and mortality to the patient. So, based on the results of the national lung screening trial, the United States percent Preventative Services Task Force made a recommendation in 2013 for low dose screening in patients aged 55 to 80 who had a 30 pack year history, smoking and rather currently smoking or quit within the last 15 years. It took about two years for the senator Medicaid, Medicare Services to actually approve low dose screening and it pretty much follow the same guidelines. The ages are a little different. So 55 to cut short to 77 years of age. Patients had to be asymptomatic at the time of their consideration for screening 30 pack years currently smoking or equipment in the last 15 years. And importantly, they included in this that you have to have a shared decision visit with the patient to talk about lung cancer screening to talk about the incidents of false positives and those that would be positive and how you're going to manage those going forward. So you have to have the shared decision visit documented in order to proceed with the screening, So the second trial was actually just published within the last year. This was a European trial from the Netherlands and Belgium. This was a smaller study, so it randomized 15,500 patients are so most of these were male. There were only about 2500 females in this trial. This was designed a little bit differently. So as opposed to low dose CT screening for 1 to 3 years, which was the National Lung Screening Trail here in the US this was a baseline scan than one year at three years and then at 5.5 years versus no imaging at all, and just following these patients clinically and getting images, if they were clinic goal symptoms concerning for malignancy, it was a lower age groups. So they went from age 50 to 74 instead of 55 to 80 and it was a lower tobacco utilization. So it creates to roughly 20 pack years as opposed to 30 pack years and again the patient had to be current or former smokers, but quitting within the last 10 years, so little nuances to how they enroll these patients, and interestingly, they used volumetric nodal analysis as opposed to just two dimensional analysis that will be important when we look at the incidence of the false positives. They also excluded patients who had a prior cancer of lung, who had a prior history of lung cancer within five years. A scan within the prior year had performance limitations that may have prevented them from having definitive treatment if they had a positive scan and or were morbidly obese just because of the quality of the scans being less with morbid obesity. And so they showed actually very similar outcomes to the national lung screening trial. So they saw a Stage one shift. They found many more stage one lung cancers and screened patients, and there was a 24% relative risk reduction of mortality in men. Interestingly, a greater mortality reduction in women that were screened we caution a little bit about that total amount and women being greater than men just because it was a much smaller population than the men. So nonetheless, there still is a relative mortality risk benefit in these patients because of the volumetric analysis, as opposed to the two dimensional analysis, which was done with our the national screening trial. There was much lower incident, false positive, so as opposed to 27% false positive and national screening trial. With this trial, there was only about a 3% false positive incidents, and there was also no reduction in all cause mortality. This may be because the number of patients in this trial was lower than the national up screening trial. So with that, um, outcome from the Nelson trial, they're actually currently within the United States Preventive Services Task Force. There is recommendation for public comment on whether we should be changing the screening criteria in the United States to those criteria. So, in other words, a 20 pack year and also screening at age 50. So that decision hopefully pending by the end of the year. So now if we look at the next question, I guess when we look at screening, how good are we had actually obtaining logos, screening and getting it done in the United States? So this is actually all the states from left to right in the United States. As you look at the bars, you can see there's a dramatic difference in the implementation of lung cancer screening and eligible patients across the states from states that look like they're doing great all the way to the right, like Massachusetts, Vermont and Kentucky to states that are doing terrible on the left, like Nevada and California. But I'll draw to your attention is if you look at the left column or the Y axis, that's percent. So that is a scale from 0 to 16, not a scale from 0 to 100. So this tells you that our implementation of low dose screening at best in Massachusetts is about 15 to 16% and the national average for those patients are eligible for screening is 5%. So pretty invisible? How about if you already enroll somebody in screening? Have the discussion with them. You get your first CT scan. Let's say it's a normal scan. We then have the recommendation to follow them up annually. How good are we or the patients at getting those follow up scans? So here this is a meta analysis, looking at a variety of different studies across screening implementation, and you can see very similar to what we had seen in that last slide. You have some studies that have shown very good implementation, which is down at the bottom and others that have shown horrible follow up. And if you look on average across all of these studies, about 50% of patients will actually have the follow up scan performed after that first initial screening CT scan. So we're not good at starting, and we're not good at keeping patients in that screening protocol. So we're Penn Medicine, right? We're supposed to be doing much better than that. We should be able to have these processes in place. We should be able to make this work for these patients and do the right thing. And the question is, do we really? So what I'm gonna show you is data from 2014 to 2018. And so this is patients who already had their first screening CT scan. What percentage of those patients go forward and have their subsequent CT scans done. And the light peach color is those patients that never have a second scan done. So if you look across the board, about 50% of the patients never end up getting their second scan, and if you look at patients that complete total screening so they get all three of those screens and continue on with it. That's the middle bar. That's about 3 to 4%. So about five no more than 5% of our patients in our system. Are we actually effectively maintaining them in the screening and recognize the dates of this? This is pre covid. And so, with covid and patients fears and anxieties about coming out and getting screening done, these numbers almost surely institutionally as well as nationally are even more visible. And so something really stinks here. So that's screening. And so I'm just going to switch gears very quickly here and talk just about to new technologies that we're utilizing if you find a patient that has a nodule that is of concern that you feel needs to have biopsy what technologies we have available. So what I'm showing you here is this is a sparrow works. This is actually what most people would call a cone beam CT scan. So this is a CT scan. Instead of having the doughnut that the patient table slides in and out of this is actually a robotic arm that has what looks like a standard C arm here. And the C arm actually is a C T scan that this spins around the patient to give you the equivalent of a C T scan. So you basically put the patient on the table, you navigate to what you think is your nodule, and then you actually next line, do a C T scan. And here you can see in this picture that this bright white line here is our device or biopsy instrument, actually in the nodule, so you can confirm by CT scan that you're in the lesion and actually getting the biopsy that you want. So this has really improved our abilities to find smaller nodule is confirmed that they were there and get a biopsy. In addition to that, within the last roughly two years, there's been approval of robotic bronchoscopy. And so there's two systems out. The one on the left is what's called the oris, or monarch system. And the one on the right is ion by intuitive. So basically what these allow you to do is steer a bronchoscopes away from the patient to the lesion and the technical advantages that's felt to be gained by this technology is that standard bronchoscopes, because of their flexibility, prevent you from actually making certain turns and maintaining the scope where you want to go. These robotic bronchoscopes have a smaller diameter, and because of the materials that are made out of, they can maintain their position to make turns that you don't want them to. Did you want them to make and allow them to maintain in position to get your biopsy? And so these are now being utilized, implemented across the country, increasingly to allow access to these smaller modules. So I guess I'll just wrap up with one thing before moving on to Dr Aggarwal is, while we're in this era of lung cancer treatment, we can't forget what are great statesmen from Philadelphia here, Ben Franklin said, is that an ounce of prevention is worth a pound of cure. So we know what causes the vast majority of lung cancer and so we can't talk about screening. We can't talk about lung cancer without talking about and addressing with our patients smoking cessation. So with that, I will stop. Our next speaker is going to be charged with alcohol. She's going to give us an update in medical oncology. Kind of where we are with, um, new therapies in the last few years and how the horizon looks brighter for our lung cancer patients. Thank you, Andy. Uh, it's really a pleasure to be here with a fantastic multidisciplinary group of speakers. Uh, I'm a medical oncologist, and I talk to you about some updates and how we're really moving the needle in treatment and management of patients with newly I newly diagnosed as well as metastatic, non small cell lung cancer. So where are we today? A couple of years ago we saw headlines, and this is a snapshot from The New York Times, where we actually saw cancer related mortality declined significantly. In fact, we saw the sharpest one year drop between 2016 and 2017. It made headlines, and many of these advances were really attributed to the decline in mortality from lung cancer and melanoma, some of which were derived from the introduction of targeted therapy and immunotherapy. Well, good news is that this trend has continued. So if you look at the cancer statistics which were just released last month, uh published in 2021 From the second graph, you can see that the incident that the incidents of deaths pour 100,000 males attributable to lung cancer in red has continued to decrease significantly. And you can see the largest decline has really come between 2010 and 2018. And Encouragingly, the same trend is also seen in women. Uh, there on the bottom graph there again, I think a lot of efforts have gone into improvement or more in mortality, not just targeted therapies or immunotherapy. But I do think that we are also, um, making a dent in terms of early detection. And hopefully the trends will continue as we increase our screening efforts. So I'm a medical oncologist and I've been doing this for some time now. And happy to say that, you know, today in today's day and age one size approach does not fit. All, um, gone are the days where we would use carbon platinum paclitaxel for all patients diagnosed with metastatic non small cell lung cancer. Today, our treatments are really varied and personalized based on um, are based on patients demographics as well as to um are characteristics that include mutation, all signature smoking history as well as the real one status. If I think about all of my patients about, um, a quarter to a third of my patients currently receive target therapy or combination targeted approaches for specific mutations that were able to find in our patients mutation signature about authority to a greater than that are able to receive immuno monotherapy, especially with the approval of agents such as pluralism, AB and metabolism have been the first line setting. We are able to avoid the side effects of chemotherapy. And now, really, the question is not in terms of who should receive immuno therapy. I think the question really in our clinic is who should get chemotherapy because immunotherapy has really become standard for patients who are not candidates for targeted therapy. So we use techniques such as PD L one analysis, etcetera, to really choose patients that may benefit from combination chemotherapy and immunotherapy. Compared to immunotherapy alone, dramatic progress has been made in terms of even delivery of targeted therapy. We used to think of lung cancer as one entity, but now we are. We have begun to dissect the pieces of the pie, if you will and have really recognized that lung cancer is really complex. There are significant number of patients that have activating mutations that, uh, lend themselves to not just a better prognosis, but our predictive biomarkers that can tell us about the response to targeted therapies as well as the biology of disease. The most common molecular alteration that we find and never smokers or light smokers is E G F R mutation, which is present in about 10 to 15% of all non small cell lung cancer, which is immediately actionable, and Target hable Uh, and there are about six different treatments that are currently FDA approved and endorsed by the FDA, endorsed by the NCC and guidelines. Um, as you will see in this table here, there are at least six other actionable targets that each have, uh, FDA approved therapies that are available for us to prescribe that have been associated with significant improvements in delaying progression of disease as well as improving overall survival. We now have five drugs for out trans locations, and as you can see many, many drugs for certain other either fusions or point mutations, I will say that care as mutation as you will notice in this pie chart does account for a third of the mutations, especially non squamous, non small cell lung cancers. And it's not immediately localized to only patients with never smoking history but can actually be found in patients with a smoking history. And most recently, we have seen encouraging data with a new inhibitor that is targeted towards a subset of KRS mutations called K R s G 12 c mutations. And we are very excited about the imminent approval of this drug called Soda Assab for the subset of patients that may have this mutation. So again, a lot of, um, activity in the targeted therapy field. And we must look for these mutations. This is just a list of approvals. Um, just to show you how much progress we are making in lung cancer. These are the approvals that came about in 2020 alone. And these are separate targeted therapies for different indications, as you can see within a short period, a lot of time that were approved between May of 2020 as well as the latest approval coming in only a few weeks earlier. Another drug format exam 14 mutations. Uh, these are not the only mutations that we care about as I mentioned here as G 12 C is one of our upcoming mutations that we are very excited to have a targeted therapy for. But there are other mutations. Her to um uh is her to over expression is often, um, target hable in diseases such as breast cancer. But we're also finding that a non small cell lung cancer her two mutations are immediately actionable with either antibody drug conjugate or oral therapies that may target them. And then less common mutations in E G f R, such as Exxon 20 are also becoming immediately actionable. So I talked to you about targeted therapy. I talked to you about molecular testing. Our traditional approach of molecular testing has really been taking a piece of humor, Um, and really subjecting that do next generation gene sequencing at Penn. We are blessed to have in house sequencing where we analyze all of our non squamous, non small cell lung cancer patients with 156 gene panel that looks for all of these mutations, and they fire me education. We offer targeted therapy based on that particular mutation subtype to really deliver precision therapy and offer a personalized approach to our patients. However, we do find that sometimes tumor biopsies are small or they contain a chronic tissue or the tumor. DNA is just not sufficient. And in those situations we have been able to utilize the power of plasma circulating tumor DNA to really use that information, amplify that circulating tumor DNA, sequence it and really derive at the same information and deliver again targeted therapy or personalized therapy. And again, this is a very complicated slide for patients that are not candidates for targeted therapy. I just wanted to stress the importance of how many improvements we have made in the delivery of immunotherapy, either alone or in combination with chemotherapy. These are all of the FDA approvals that have come in within the last four years, as you can see, right up on top, uh, in October 2016. So almost 4.5 years ago, we saw the approval of federalism at for first line treatment of non small cell lung cancer, and that has completely changed the way we offer these therapies to our patients. We really think about what their molecular signature is what The PD l one status is smoking history and then determine whether or not to proceed with chemo or just proceed with immunotherapy for our non target Double indications. So I'm often asked how we're able to do this during covid 19 Pandemic. Um, we at Penn and my co authors are on the call with me here. Created a set of multi disciplinary guidelines to really guide the management of safe delivery of lung cancer care during the pandemic. Um, you know, we This was published in the Journal of Clinical Oncology Oncology Practice and where where we are is really different from where we were in April of 2020 when these guidelines were published. But we do follow some of the same principles in terms of screening our patients. Um, questionnaires are still in place. Uh, we also make sure that we are, you know, referring for testing. If there are, uh, suspect suspected symptoms and then we based on the clinical symptoms pathology as well as the testing strategies, continue or initiate therapy as planned in our guidelines, we did go over a certain stage based scenarios which are outlined in the next slide and here, you can see we really thought about multiple different clinical scenarios, um, and made recommendations for either coming in with, uh, stereotype. Active body radiation therapies for our stage want us during the time. And we weren't really doing a lot of surgeries in our initial lockdown to really thinking about delaying, starting of concurrent chemo radiation or using sequential approaches for our Stage four patients. I will emphasize that there are a few new strategies that came into place, especially based on new FDA approvals during covid, one of which was the availability of Q six weeks. Petrol is a map where I am using this six week regimen for my patients who have had a phenomenal response or have partial response or have been on therapy for a very long time, and I'm using the 400 mg does. I would also like to mention that for small cell lung cancer, we have availability of both the four week their value map as well as the four week Tess Elizabeth, uh, four years in the maintenance setting for our patients with extensive state small scale, and I certainly used that, especially in the pandemic. We've utilized our home and fusion program and have heavily relied on using telemedicine to give both our patients as well as our staff safe, so in in summary, I think Covid. 19 has really changed the landscape of how we are delivering clinical care. Um, we are weighing the benefits of cancer and covid 19. We are stressing, um, the delivery of vaccination for our patients. In fact, then, medicine is vaccinating high risk patients, and patients with lung cancer are the highest risk patients. So we are stressing the importance of vaccination and then really carefully considering which patients should come in and which patients should be seen via telemedicine. With that, I will stop. I'm happy to take questions towards the end, but I wanted to introduce my colleague and friend Dr Abigail Berman, radiation oncologist at Penn, who will talk about radiation for lung cancer during covid 19 and beyond. Thank you. Great. Thank you, Charo, for the introduction. And, um, thank you all the Panelists for joining in today, um, as well as the attendees. It's wonderful to see so many familiar names as well as new names. So thank you for taking the time to join us. So I'm going to give a little bit of a introduction to what lung cancer care looks like in 2020 2021 based on a few cases. So, uh, just this is a gentleman who came to me 85 year old, uh, male, who's a former smoker, and he had a growing right upper lobe lesion. We did a further work up. It was f d. G. Added. It was deemed not able to be biopsied. And he came to me and and said, You know, what are what are my options? So, um, of course we sent him to our surgical colleagues, uh, to consider surgery versus stereotype Actiq radiation. And our surgical colleagues did not feel that he was fit for surgery. So we talked about the different options for radiation. So going on to the next slide, you can see that, um, putting this into the context of lung cancer care during covid 19. So this comes from the same paper that Dr Aggarwal mentioned where we talk about how if, if any in any way, lung cancer care needs to be modified in the context of covid. And you know, we were really fortunate that we had safe protocols and, uh, that are surgery, uh, and that our surgical colleagues were able to continue to operate throughout covid. And of course, you can continue to, but it's wonderful to have s p r t as an option for patients who, um, could not cannot undergo surgery going on to the next slide. So what is s PRT? So s PRT is the delivery of large doses of radiation to a small treatment volume. By definition, we are employing multiple beams, um, and, uh, for building as well as technical reasons. It is, by definition, using less than or equal to five fractions. And this is just an example of r S P R T treatment. So I mentioned that this patient who I saw couldn't undergo surgery. But what about the patient who comes in either during covid or, um, not in the context of covid and says, um, you know what? Which is better for me Surgery versus S P. R. T. And you know, we really we don't have the answer to that. And there have been multiple trials that have attempted to answer this question. These were two trials, one of which was done in the United States, one of which was done in Europe. And they both failed to accrue enough patients to publish on their own. And they did actually have pooled analysis. And the pooled analysis, um, obviously has its, uh, flaws based on the fact that this was not one trial that was appropriately analyzed, but it showed that, uh, stereotype tactic radiation was certainly a very good alternative to surgery. Um, for these patients with stage one disease, even if they were operable. So, you know, in the context of covid, this was helpful data. You know, if if we couldn't operate on the patients because of covid or simply because they were medically inoperable, um, we are able to tell patients that we have a really, really, really good alternative. So, you know, one thing that comes up both for patient convenience, um, in the Arab covid as well as outside of the Arab Covid is, um how many fractions do you really need? And, you know, while all stereotype Actiq regiments, which are five fractions or less, are relatively not very time consuming, Um, there is actually nice evidence to even give single fraction Um, s P r t. And this is a publication from 2000 and 18 that came up a lot this year to say, um, is it safe? And is it equally efficacious to give single fraction S P R T. And, well, we don't tend to do this a lot at Penn. Um, because of technical considerations and others that I'm happy to discuss more. Um, it is a very, very good alternative. So are we ever going to understand or know the answer to, uh, whether s p r T or surgery or equivalent while there are a host of ongoing trials that are accruing And, um, we hope to have even more insight into this process. But, um, in the meantime, we are pleased, you know, to be able to offer this as a patient at two patients, Um, for whom? It is a very good alternative. Next slide, at least. So just, uh, you know, to to talk about what's on the horizon. So, um, you know, for all of our stage one s p r t patients, we actually offer them, um, a study that we have open on as a randomized pilot looking at the role of the microbiome, Um, in conjunction with radiation where they're actually randomized to getting antibiotics or not to see whether or not that changes the immunological Amelia, um, and alters the outcomes after stereotype Actiq radiation. So Well, we already have excellent outcomes, always trying to improve it. And the microbiome There's excellent pre clinical data to support that. So the next case I wanted to talk about was a 65 year old female with a stage three non small cell lung cancer who came to me. And, um, you know, again, this was this year in the context of covid. And, you know, we we certainly are, are lucky that we were able to employ all of our protocols and and not delay any of these patients. Certainly not a stage three patient and even the stage one patient that I previously showed. Um, you know, if we are concerned that there is truly malignancy and feel that there is proof, we do not want to delay them as a result of covid. So next slide if you, you know, think about our Stage three patients, we know that the best treatment for them is chemotherapy and radiation given concurrently. Sometimes we are able to add in surgery if the patient is inoperable, Kennedy And if it makes sense to do, try modality therapy. In this case, the patient was not a good operable candidate, so we settled on chemo radiation. And, of course, the Pacific study showed us the value of not just chemo radiation but giving their value map after chemotherapy and radiation accidentally for one year with a significant overall survival as well as progression free survival benefit. So what does this mean for radiation? Well, it used to be that we were just giving chemotherapy and radiation at the same time. Now patients are getting more therapy than ever. They're getting immunotherapy. In addition, patients are fortunately living longer. And of course, we have the underlying concern of COVID 19 and all of this. And you know, really, our priority to maintain their pulmonary status as excellent as possible is really important. So we're more concerned about toxicity than ever, And you know, one way that we are really, fortunately able to combat this concern at Penn is the use of proton therapy. So just a few benefits of Proton therapy So, First of all, some of the best data that has ever been published in Stage three disease historically was using proton therapy with chemotherapy. And it even, you know, half a decade ago showed a median survival on the order of 30 months. In addition, we have an increasing awareness that radiation has the potential for significant cardiac toxicity, something that we, as radiation oncologists were not always very attuned to in the past. And Proton therapy has an excellent capacity to be able to lower the cardiac dose. And we have good data demonstrating the exact numbers that we want to keep the cardiac dose at or below. And that's very, very helpful. Of course, the other context is you know, that this patient said to me, So how long do I have to come in for and how many treatments? And I told her I said, You know, our our standard would be six weeks of daily radiation therapy in your case, and she said, Well, you can't you do it any faster and I wanted to highlight the fact that there are multiple studies, only one of which is shown here using proton therapy in a more what we call HIPPA fractionated way or fewer fractions, but larger fraction size. And, um, while data is still developing and forthcoming in the right context, I have been willing to give chemotherapy and radiation concurrently with a fewer number of fractions and larger fraction size. So again, you know, fitting into the context of lung cancer care in 2020 2021. Well, proton therapy really does add to our ability to potentially do hypo fractionated radiation schedules. And at the height of covid, when we were so concerned about the number of times that a patient had to come in and see us, this was really a helpful option to be able to consider and give hypo fractionated radiation. So I also just wanted to highlight the really important role of protons in Rio radiation. So, you know, oftentimes, if a patient has a recurrence there told we can't you know, the radiation oncologist says, we can't radiate you again. We are up against our constraints. We just can't safely do it. And the good news is that protons has a really strong role in the context of rear radiation. We actually have a study open here at Penn, where we are giving Proton irradiation with or without concurrent chemotherapy and then followed by a year of consolidation. Pebble is a map, and there are a lot of, uh, this study has been enrolling well, and and obviously it's been a great source of support as well for our patients in our network who potentially cannot do not have another good treatment option. Of course, we still have a lot of questions about the rear radiation setting. So, uh, you know, we are still defining how much radiation truly can be given safely in the rear radiation setting, and that's an important goal of this study as well as other studies that we have. We also have questions about the correct systemic therapy and the timing of this. So here it's given as consolidation kind of similar to the Pacific trial, but in the real radiation study. But is there a role for moving? Pemberley is mad, or any immunotherapy concurrently, Um, And first, of course, we need to answer that question in the primary locally advanced literature. But then we can also look at it in this context, So just a few take home points so Covid has presented significant challenges for lung cancer patients. But it's also been really eye opening experience to highlight some of the unique advantages of radiation, as well as some of the data that we have that allows us to more seamlessly take care of these patients. So S P R T is the standard of care, as we know for inoperable stage one lung cancer, and it can be safe with acceptable dose constraints. And then, of course, we are investigating it in operable stage one lung cancer and can be a very good option. Um, where patients either refuse surgery or for whatever other reason, it is not an option. Proton therapy may decrease the dose to critical organs, including, of course, the lung, but also the heart, which we have an increased appreciation of as an organ at risk in locally advanced, non small cell lung cancer. And of course, we also have developing data that we can give potentially fewer fractions in the proton therapy context, which, you know may really improve the patient experience, certainly on the horizon. We've got the microbiome study that I looked at and the evolving role within all of lung cancer care and more randomized data between surgery and radiation, hopefully in the operable population to shed more light on how we should care for each and every patient, as well as the role of real radiation with Proton therapy, um, and immunotherapy. And it's really critical critical role. So I want to thank you very much, and I will pass it back to Dr Car Check to talk about covid 19 vaccination guidelines and prioritization and happy to answer any questions later. Thanks, Abby. Um, if you have any questions, please feel free to put them in the chat. We already have a number of questions there, and it looks like some of the Panelists have already answered them. Um, I just wanted to briefly touch on the guiding principles for care of our cancer patients, as well as, um, how we strategize with our patients during the time of covid. So obviously we still want to maintain our high standards and quality and taking care of our cancer patients. But at the same time, we want to protect them from covid infection, especially our lung cancer patients. They are particularly susceptible, and the combination of lung cancer therapy and can accommodate covid infection is a deadly one. And we know that from a lot of the information that has come out of Asia and Europe. Um, so we've really tried hard to strategize about ways to reduce the complications of covid infections in these patients while at the same time protecting each other. Next slide. Um, so our goal is to vaccinate as many people as possible. This has been difficult. You know, Philadelphia is a carve out. So Philadelphia, the Department of Health takes care of their own vaccination program. The rest of the state is really run at the state level through the local county health agencies. Uh, and it's been difficult for patients difficult for them to figure out where they can go. Some of the websites have been up and down and very slow. I would encourage you to think about, and there's people on the call from different states as well. So I encourage you to really look onto the websites, um, for your area. It can be very helpful to the patients if you can, uh, push them in the right direction. Um, a lot of patients ask well, which vaccines should I get? And my standard answer to everyone is whichever one you can get first and that will become more and more important this weekend. They're probably going to approved the Johnson and Johnson vaccine, and the other major happening in our area is within the first or second week of March. FEMA's gonna open up a mass vaccination site at the Philadelphia Convention Center. Um, so this is a very moving topic, and you will get lots of questions from your your patients. And so I think it's important to try to evaluate yourself, uh, with as much information as possible Next slide. So, um, Pennsylvania overalls in phase one New Jersey is a little bit ahead in phase one B now, and I believe Philadelphia is moving to phase one B. Um, but basically, you can see our patients fall into a lot of these categories. Um, so 65 older patients with cancer and also you can see the red box patients with an immuno suppressed um immuno compromised state, and that includes the use of critical steroids, which some of our emphysema patients are on as well. Um, other risk factors include smoking and diabetes. So these really affect a lot of patients that we see and manage. And so we're really trying our best to help them secure vaccinations as quickly and as easily as possible. Here. You can see what the Philadelphia Department of Health Guidelines are, Um, and there is a subset of patients with sickle cell. Those usually are younger patients, Um, not our lung cancer patients. But those are also being vaccinated. A pen. You may have seen an article about the university and vaccinating some researchers that was in the Philadelphia Inquire. My understanding is the article was a little bit unfair. Those were researchers, and yes, they were vaccinated out of phase. However, they were researchers working on covid, um, and virologists working on COVID. So I don't know the exact details of it, but, um, in general, the health system and the university has been really abiding by all the strict guidelines that have been set forth for the distribution of the vaccinations. Next slide. Um, so again, here you can see the risk factors, and obviously our patients are greater than 65 patients on active therapy. Um, and another question your patients will ask you is. Should they get treated while on active therapy and we have some other slides that will go into this. But the answer in general is yes, Um, and certainly patients with lung cancer. Um, so these are the kind of recommendations that we go by which are also supported not only by national guidelines, um, but also supported by the National Cancer Collaborative Network. The N C C n um, And as you may not know, many of the people on this call sit on the committees and subcommittees of the N C C N, which is located Implement meeting. Um, and they're trying to make a push as well for code vaccinations in cancer patients. Um, so and especially an active therapy. Um, a lot of people ask the question, What about the immune response? Will it be as robust? And the answer is probably not for patients that are actively receiving chemotherapy, especially those that are immuno suppressive. Um, but it's still probably better than nothing. So, um, the current recommendation is that there's no issue in the timing of the vaccine in relationship to their treatment, so you can vaccinate somebody on the same day they get their treatment, including radiation. Um, remember that the exclusion criteria we've gotten this from a number of people is if you've had a covid infection, Um, your vaccination should be delayed for three months. Um, and that's for a number of reasons, probably the most important of which is you already have protective antibodies. And so by pushing you three months later, it opens up more vaccine for other folks. Some special considerations for those folks having bone marrow transplants and car T cells. That's not really, uh, germane to our patients. Um, in general, after an operation after a surgical operation, we wait about two weeks. Uh, we do know that just surgery in and of itself produced a lot of cytokines and is, um, immuno suppressive. Uh, so about the two week mark is when we're recommending patients get vaccinations if they haven't been so pre operatively. Um, we have actually delayed a couple recently a couple early stage patients in order to get them vaccinated and get their vaccinations complete before surgery. Those are people who you know, a 4 to 6 week delay really won't have any German effect next slide. So, um, here's the guidelines. We don't have specific guidelines for vaccinations in neutropenia. Um, it does make evaluation of their fever more challenging. You don't know if their fevers from the vaccine or if it's a neutropenia fever. So we just keep that in mind. Patients who are thrown beside a pedic we vaccinate without consideration. That's very low volume. There's almost no bleeding effect. Um, as you know, management and fever, fever and chills are very common side effect, especially people have complained about it with the second dose. I was a little concerned because I had absolutely nothing. I was concerned I might not have reacted. Um, but we just treat those either expectantly or with some antibiotics. Um, And so, um, I think there are patients who will have special concerns. You see, sickle cells, one of them, Um, but in general again, I think for our patients, when they ask us, when should we get vaccinated? Our answer is almost always the same as soon as we can possibly get you to a vaccination site that will administer it. And the second is which vaccine should you take? And the answer is whichever one you can get next slide. Mhm. Um, there are a number of vaccination tools you can use, uh, to try to see where people fit in. There is a state one. This is the eighth facts, which is more of a Philadelphia one. And you can plug in the criteria, Uh, and it will give you, um, exclusion and inclusion criteria, and it puts you into a group. So that's one of the things I said, especially with our older patients just having some general familiarity with the websites, either for the Philadelphia Health or for the for the county health throughout the state. It's very helpful if you can direct some of the older patients, especially to those sites, and tell them what to expect and and tell them how to sign up next slide. Um, finally, you know, there's a lot of talk about physician physician burnout, um, and physician well being and nurse and practitioner wellbeing and our health system. And I assume a lot of health systems throughout the region have recognized this as having a major impact. Um, and it kind of plotted out, you know, when? When it first when we first hit the pandemic, it was kind of fun because we had a special pass that we could drive down the road and we could go into the hospital and nobody else could. And we had a thing that said we were an essential worker so you could cross the bridge to New Jersey. We got emergency privileges in New Jersey, so at first we were a little bit heroic, and then we kind of had a honeymoon. And then we were in the during the summer and early fall. We were like, Oh, my gosh is just never gonna go away And we had some triggering events, which included the kind of the second wave and kind of some upticks. Um, so it's important to think about these things. And there are a number of programs provided through the state, um, medical boards to help people address these and to help healthcare professionals address them. But I think it's important because we all do realize if we don't take care of ourselves, we're not going to take care of our patients. So this is an area that's kind of new and emerging, and it's probably a secondary victim of the overall pandemic next slide. So I hope today that in the past hour you've gotten some sense of kind of help. Our lung cancer care has evolved during the pandemic. Um, you know, initially at the onset, we spent a lot of time and effort, uh, into really modifying how we did things. Making a lot of contingency plans. Um, as things stabilized, we kind of tried to strategize how we could get back to normal, how we could get back to screening our patients. Very important how we could get back to timely diagnosis. Um, you know, it's interesting. There are a lot of things that really came into play, for example, are highly trained. Um, interventional pulmonologist were kind of called back to the I C. U S. To work on on some of the critical care for covid patients. Um and so we had to figure out ways and and thoughts about how we were going to get some of our diagnosis made and similar with our medical oncologist. Um, even some of our surgeons were redeployed down two tents outside the emergency room for triage. So as covid stabilized, we got people back in, but we really had to work on strategies to get things moving in the right direction. I think in our current state, um, internally, we are back to to what I would consider our baseline. We can provide the full gamut of care to our patients. Um, the public in general has not totally come around. I think maybe not so much in our direct patients who are already in the cancer pipeline. But when I go out and added about and I'm talking to primary care physicians and especially pulmonologist who, uh, kind of deal with a lot of long term pulmonary patients, um, that's where we're kind of haven't convinced people to come back yet or convinced it's safe. And that introduction into the pipeline is the important part. And that's kind of where the lung cancer screening gets involved. And that's what allows us to find these very early stage patients. So I really appreciate you spending the hour with us. There were a couple of questions, um, that have gone through the chat box, which have already been answered. The time is late. If anybody has a last minute question, we would be more than happy to answer it. Otherwise, we really appreciate all of you joining us. If you require any other information or want to talk about any of the issues or talk about anything, please feel free to reach out to any of us. Uh, we'd be happy to do that. So thank you all very much and we can end it there.