A panel of experts answers all the current questions on breakthrough infections, who needs boosters, whether to keep recommending masks, and the future of variants, with a spotlight on meeting the needs of the immunocompromised, such as organ transplant recipients and cancer patients. Bonus: what to know about molnupiravir to treat COVID-19.
we'll go ahead and get started. I'm hope you go professor of medicine and and breast cancer oncologist at UCSF's cancer center and I'd like to introduce my colleague who is leading the cancer center ground rounds effort and we're working together on this program, dr Laura Criscito, who is the vice president and chief medical officer of cancer services at UCSF health and she'll talk to us in just a moment. Today's live series. We'll talk about the status of the pandemic and effective vaccination. We'll talk about the immune responses in immunocompromised patients which represent our patient population and cancer medicine. Um and we'll talk about integrative oncology in a very important area for our patients and I think increasing importance. Um are this live series is also recorded and will be available on the cancer center after the session. And uh with I think a few days to get it on the website. Um and with that I'm going to turn it over to laura to talk a little bit more about our series over the course of this year. So welcome everyone and thank you for joining us. We're really excited to have a great lineup for this year. So um please look for future brochures and information about our other series coming. We will have three more over the course of the year with important updates in various areas of oncology, both surgical and medical oncology. Um and uh I hope that you know, we have a really exciting lineup today as you'll see. And this is just a taste of what's to come. So um thank you again for joining and enjoy. And lastly I'm just going to share the disclosures for our speakers tonight. So thank you and welcome. All right, thanks very much laura. Can you go back one slide before we um start? Great thanks. And so what we're going to do, we really have an exciting lineup of our colleagues who have donated their time to talk this evening and our organizer Alison will potentially be able to share a link for where you can look for the recorded session afterwards. Also that you would be able to share with others. I think everybody knows Monica Gandhi who's a clinical professor in the Department of medicine and director of the UCSF Center for AIDS Research as well as our ward 86 HIV clinic. But most importantly in talking about the state of the pandemic. She's been one of our major spokes persons for the pandemic and is frequently on the news, talking about what we're doing and where we're going and giving advice. So we're really excited to have her with us to talk about the status of the pandemic and vaccinations. And then we'll move into COVID-19 vaccination and immune responses in immunocompromised patients. And we have Monica Phung who is an assistant professor and associate director of transplant infectious diseases, basically caring for patients who are immunocompromised from transplant um And then timothy Henrik who is associate professor in the division of experimental medicine um and runs a program looking at long term effects of Covid actually um a grant funded program. So we're really excited to hear from both of them. And then lastly, but certainly not least a leader in the field of Integrative Oncology I think, well known to everybody Donald Abrams who's a the immediate past chief of hematology oncology at Zuckerberg san Francisco General Hospital um and works as an integrative oncologist at the Osher Center and is now a professor emeritus but still clearly seeing patients. So we'll start and I'll hand over the podium so to speak to Monica and the slides now remember I think just as Monica gets started in the bottom of your screen, there's a little button that says Q. And A. Um Put in your questions into the Q. And A box. Any time they come up, you don't have to wait for anything. Well, plenty of time to discuss the questions you have. Um And I'll look for those questions in the Q. And A box. Well, thank you so much for having me and I'm going to talk about vaccines in the state of the pandemic and talk a little bit about what vaccines do. And then turn it over to my colleagues in infectious disease to really talk about specifically immuno compromised and transplant patients. So, you know, in terms of the vaccines for Covid 19 which were really developed in record time. We have pretty much nine that are most actively in circulation and the three that we have in this country. We're really familiar with the two on the top or the MRNA vaccines. And the third one is A. D. N. A. And no virus vaccine. But there are other vaccines that are really in circulation. Novavax is an interesting one that may be coming. And the others have been used in different parts of the um world and really out of those nine candidates that are the main ones, six of them involved somehow the spike protein of the virus. So what that means is there's the virus and then there's the host cell and then the spike protein comes out from the virus and sticks to the hotel um and connects with the receptor using its receptor binding domain. And six of those vaccines either code for the spike protein or in one situation actually gives people the spike protein. And the three other vaccines that are out there in the world, one from India called the vaccine and tube from china the sinovac and sinopharm involved whole inactivated virus. So killing a virus and giving the whole thing. So if we drill down a little more on this the spike protein vaccines remember that you've heard a lot about the two that are M. RNA vaccines and the reason is they're just they're they're new in terms of the world of pathogens. But they have been used. They actually have been Thought about for the last 10 years and they were developed in response to another severe coronavirus infection murders. But they didn't need to be used. So what they code, what they really do. The Pfizer moderna. We use these brand names at this point is that they give you the MRNA that inside a little little lipid membrane that will code for the spike protein so that MRNA is injected into the body. You take it you translated into the spike protein. You raise an immune response to it. The spike protein and MRNA degrade and go away and then you raise a nice immune response to it and that's your immune response. And it's really an incredible advance. And then these three on the top johnson and johnson Astrazeneca on Sputnik five. They involved are also quite unique. They involve the D. N. A. Of the spike protein inside of benign adenovirus or cold virus that doesn't replicate in the body vector. And then that DNA inside your body goes to M. R. N. A. And then again you make the spike protein, you translate it and you raise an immune response Novavax which is coming probably in India the soonest um is the most traditional of the vaccines. If we think about like diphtheria pertussis um it's really just the protein itself connected to an answer them. And I have to remind you before we can get into them. You know compromise what you all learn in the next talk and hear from um Monica and tim is that is this sort of immune response against vaccines um and really that there's sort of two major uh cells that lead that are developed in response to vaccines. One or B cells which are the ones that make antibodies but they need T cells to help them make antibodies. And importantly memory. The hopefully the B cells will go into memory or that's at least your hope because then when they go into memory they can be stimulated and produce antibodies. If they see the pathogenic it importantly those antibodies will go down to go down the time. That's totally natural. You can't keep all that antibodies in your bloodstream from every infection or vaccine you've ever seen. But they go down the time. But then if they see the path in it. But again those memory B cells will make more antibodies with the help of T cells that respond to the pathogen. And then T cells are also formulated in response to the vaccines kill ourselves to toxic T cells Cd four cells help our cells And we and these are really the main immune response that help modulate Our long term. I hope protection from severe disease um from the uh from from the stars Kobe two virus. We have plenty of data from other infections and from this infection that t cell immunity and a lot of great work that dr henrik does dr daddy around here at UCSF um that really the T cell response to the vaccines modulate severity of disease. That if you have a good strong T cell response that you will be kept from having severe disease. And the T cell responses at least in um competent hosts look like they really last a long time. They have a very kind of slow half life. So hopefully they're around a long time. And we saw that even before we had vaccines. So why do we how do we know that these vaccines stimulate T cells and neutralizing antibodies? Because I'm like when we were developing like say the measles vaccine in 1963 they took the time in the phase 12 trials to measure T cell responses even though they're hard to do. And it takes some someone impressive like dr Andrew to measure them. Um They actually took the time to measure T cell responses. If you look at the fourth column here in the phase 12 clinical trials from Moderna Pfizer johnson johnson and all of them. They produce strong neutralizing antibodies but they also produce to varying degrees and various types, mostly the right response for cd four cells and cd eight cells as well. And because that these are all the clinical trials of the vaccines because those T cell responses Protect us from severe disease at least in the clinical trials that were really high levels of protection from severe disease. That's the yellow column almost 100% across all of them though. The protection against more mild disease varied. And we'll talk about that when you talk about antibodies. Um and that was true of the whole inactivated very honest as well. So will vaccines work against variants um which we'll talk about more in the next talk as well. Well we're really in the Delta era. Hope this is the last era. But remember there was these alpha, beta, gamma, delta, beta and gamma did not cold in the United States. They really weren't just transmissible. Alpha was very transmissible and delta is the most transmissible at all of all. But DELTA was first seen in India in early March. So this really has been the dominant variant for now so long from March to october and it really is a very highly transmissible variant. But if you think about what the variants do they actually involve the spike protein? Because that's going to be the part of the virus that mutates more readily to try to. It's what you know, again binds the host cell and the delta variant has like 11 um for example, mutations across the spike protein. But when you think about how complex the T cell responses um that you get either from natural infection or the vaccines, it's really much more complex than just 11. Um just just working on one tiny part of the spike protein. So for example, um there are multiple episodes across the spike protein and at least data from both here and also La Hoya Technology Institute show us that there's a very broad T cell response across the entire spoke to spike protein. So say you lose 11 of your T cells because they're mutated or they don't work very well against the delta. Very hopefully you have 75 or so they're still there. So really a very broad kind of multi uh complex T cell response across the spike protein um that we saw from natural infection but then also from from vaccination. These are data from um dr Ron here and also from the LA immunology institute that shows that T cell reactivity reactivity is really preserved against the variants and are vaccines waning and effectiveness with delta. Well we kind of need to know what we mean by the word waning and what we mean by antibodies and T cells and and severe disease versus more model disease. And so we do have to discuss, go back to the immune system and discuss it still persistently. You know, the level of vaccine effectiveness is not just based on the kind of vaccine you get. It's not just based on your individual response but which is a very important. It also depends on the vaccine that you get. If you give the vaccine sometimes too soon then your antibody response may not be as robust as if you give the two vaccine doses with more spaced out dozing at least. That's a traditional principle of vaccine ology. Um uh and also just literally just being around a lot of virus you can have a good immune response. But if you have a lot of circulating virus around you then you're more likely to have a quote breakthrough infection or at least break through some of your initial defenses because you're just around so much virus. And so for example in India at the beginning of the delta variant search which is really terrible. Uh started in early March. There were there were health care workers who were fully vaccinated that they were surrounded by a lot of virus and thus more likely to get sick. And that was to a polio vaccine. And that was true. It really depends on how much speculating virus virus, which is why camping down transmission worldwide is paramount. So in terms of I'm sorry, this little blurry but in terms of our vaccines waning and effectiveness with the delta variant, it really depends on what you're measuring. Um I really admired the FDA meeting that was held on september 17th which was there to review the need for the general population to get boosters in our country versus selected populations had already approved boosters for even know compromise. Our third dose bring no compromised patients which we'll talk about the next talks but this was really quite a tour de force to put together 74 studies across the world. The U. S. U. K. Canada Israel Guitar Singapore. This was presented by dr Jonathan Sterne at that meeting And looked and looked at the effectiveness against severe disease or hospitalization and the vaccines up to September 2021. We're holding up very well. Um so really around 90% or higher in general against um protection against severe disease. And there was just data from new England Journal today among health care workers that showed us the same thing. So really durable and great protection and severe disease. The variability seems to be occurring more in the initial protection against more mild infections. Uh And this is just data from the United States. There's mult multiple sets of data but these are two. This is one example that this was data from L. A. And uh presented up to july 25th when the delta variant circulating and you're 20 to 29.2 times more likely to get hospitalized unvaccinated, been vaccinated during the California delta surge. So really protective effect against hospitalizations from the vaccines. And then this is important because it relates to a couple of things coming up this um this month which is what this was nice data was presented on september 24th from the CDC about what's the relative effectiveness the three vaccines That are authorized in this country against that really important outcome of hospitalization and Madonna was holding up the best in terms of having a 93% effectiveness against hospitalization fighter was 88%. But Johnson and Johnson which is only a one dose vaccine right now It was 71%. Protection against hospitalization. So had absolutely rain by the end of August with that one dose um in terms of protection against hospitalization in this 18 state study. So why in the time of Delta do we see so many more symptomatic disease? Not necessarily breakthroughs in terms of more severe disease? Well it certainly could be that Delta has a higher viral load. I also think it's more likely that of course again your antibodies do wane with time antibodies are present in both the bloodstream which R. I. G. But even I. G. Goes into your nose and then GM were produced by the vaccines. We had really good data around that but I G. M which is a mucosal antibody will also win the time. And so in some cases we gave the fighter vaccine every three weeks apart actually in most cases at least in the U. S. And Israel the UK and Canada spaced it out more. And there was data that showed that giving um Fighter vaccines more spaced out. We're more photogenic in terms of antibody production. And there did seem to be less symptomatic breakthroughs using Fighter in those two countries than the ones like the Israel Israel in the U. S. That kept them at the three week duration. There was a male clinic study that showed there was less reinfection with Moderna than fight sir at least in terms of these mild breakthrough infections. That is likely because Moderna even that one week is helpful to have more duration between the two doses. And also it is a higher dose that's 100 microgram instead of Pfizer which is 30 micrograms. And again these waning antibodies and your susceptibility to more mild infection. More of an easel and upper respiratory infection. Our normal not a glitch it's happening with time our transmission rates were not down low enough that they were in other countries by the time delta hurt hit us. Um But they are they if you have a functional and tattoo mean system even after two doses they should be made a new by memory B cells. If you see the pathogen again. Yeah. Um And so what about the question about boosters for everyone? And where did we end up on that? Um You know again this is what vessels does this went out of business too. So you see a pathogen they rise then they go down with time totally normal. Then you have your memory vessels that are there and they're ready If you have an immuno competent immune system. And then the second time you see the virus you will produce antibodies at a higher level. The intriguing part about this though I guess it shouldn't be that amazing because the immune system is amazing is that we have several studies, University of pennsylvania Oregon, health sciences that show us that those antibodies that you make, if you see the virus again are actually adapted towards the variance. So the antibodies that you make will be adopted towards the delta, it's not that different from the alpha. Um and so they will you will evolve and produce antibodies that are adaptive. It will maybe take you a few days to make those antibodies from memory B cells like 3 to 5 days. So again, you could be susceptible to a breakthrough infection while you're amping up your antibodies. Hopefully those t cells and immuno competent system are staying there to prevent against severe disease. So should we give booster as well? Um you know, this was quite um this ended up not being the same the right talk. I'm sorry but I will say let me just Confirators. Sorry, okay, I may end up needing to come back to this. But right now I think I'll reserve this for my colleagues that that that boosters are approved for immunocompromised populations and won't go through those because my colleagues are speaking next but also those age 65 and older. Um and uh those medical conditions between 18 and 64 and back to that idea that if you have a lot of circulating virus or you're surrounded by more viruses are more susceptible to break through those who have occupational exposures like health care workers or or first line responders certainly uh those six billion doses have been administered worldwide. And this was a big argument when it came to this question of giving everyone in in rich countries. Third shot versus global vaccine equity. We are truly at a point this pandemic um in a way that I would call it a profound moral and ethical failure that we have given out. Only about now. We're up to 4% of the doses available in the world to low income countries. So this is this is we are now october 2021 of the pandemic december 14th 2020 was the first time we have had a uh you a the fighter. And uh we are we are at this degree of global vaccine inequity in terms of the question of vaccines, reducing transmission. They do but less so with delta. And so to explain that again it's kind of going back to these antibodies and T cells. But we did have a lot of plump nice antibody production with at the beginning, right after getting our vaccines and there was a lot of data that showed that GM was produced by these vaccines which are getting mucosal antibodies and that your I. G. Which is in your blood also go into the mucosa like your nose. And so there was a time before antibodies were raining that you were really protected from any sort of infection even having a mild or asymptomatic infection in your nose. And so with the alpha berry ain't. There was a lot of data that showed us that the risk of getting any infection including just asymptomatic just swapping people's noses after they had had infection. Sorry after they've had the vaccine like health care workers that it was very unlikely to have even asymptomatic infection in the nose. And this was really the data that led the CDC to recommend on May 13 that masks aren't needed for the vaccinated because it seemed you were so unlikely to pass it on to others if you have been vaccinated. But those antibodies rain. That does happen with time. And what happened was there was an outbreak and um it was it was a confusing messaging by the C. D. C. At the end of july because this was a very peculiar circumstance. Anyone who works in HIV medicine knows what p town is. Um but it was it was it was it's a lot of fun but it's a it's a big kind of activity on around july 4th and lots of people congregating both vaccinated and unvaccinated at the same time. There was no masking at that time because again that had been relieved for vaccinated that happened to be raining. So the windows were closed. A lot of inside activity. A lot of intimacy and there were a lot of symptomatic breakthroughs doesn't seem to reflect the number of symptomatic breakthroughs that you can see typically with Delta because this was a peculiar circumstance and the important one important part of this of this provincetown outbreak is the vaccines held up really well against severe disease though there were a lot of breakthroughs, no one, there were a couple of people who had severe disease and went into the hospital but they came right out if they were vaccinated. Now in terms of this question of okay can you spread is equally um if you are vaccinated and unvaccinated, you know that was a message that unfortunately I think got distorted by this um by the reporting from that outbreak there was a Singapore Delta breakthrough outbreak just the next day but that was reported just the next day after the provincetown outbreak that showed us that Yes you're what's called your cycle threshold of your PcR test the number of times that the PcR machine has to cycle before it goes ding and shows you that you have a you have a virus in there. If you cycle a lot to get to that viral load that means your viral load is low because it takes a lot of cycles. And so at one point in time with a vaccinated symptomatic breakthrough with Delta, the cycle threshold may be the same as unvaccinated person but then this green line shows us that the barrel load does go down more quickly among those who are vaccinated versus those who are unvaccinated makes sense, Your again, your immune system should kick in and again takes a while to produce the antibodies from memory B cells T cells coming in and you should bring down the viral load in your nose. So this was a serial testing study out of Singapore. And then this was a study that looked at 161 uh delta symptomatic breakthroughs among backs needed healthcare workers. Um and they and they had symptomatic breakthroughs for sure. But when they cultured the virus, they were less likely to have a cultural bull virus or one that was likely infectious because again hopefully was being attacked by your immune system after vaccination. So it was more sick. The virus is more sick. So yes, I do think vaccinated people can spread if they have a symptomatic breakthrough but probably less than unvaccinated. And then there have been multiple sort of contact tracing studies which are really the best way to ask are you spreading if you're asymptomatic and your vaccine, if you feel perfectly well and you're vaccinated and at least studies from Singapore, there was no study in in pal Canada. Another study at Harvard, another study at Oxford didn't seem that you spread very much if you're asymptomatic and vaccinated, which is very different than if you're unvaccinated. So hopefully if you feel well and you're vaccinated, that's when you're just fine around others. Um and then finally the CDC breakthrough data, they do keep track on their website. This is the website down here of the severe breakthrough infections that we've had after full vaccination. And so out of 183 million americans were fully vaccinated against Covid there have been um uh just over 13,000 hospitalized breakthroughs that's a rate of point oh 8%. So it is much lower than of course the rate of getting sick if you're unvaccinated. Um But importantly they did break that down that data by age and 69% of those individuals are over 65 then to to have a covid related death after vaccination is rare. Still about 22 and a million. Um and uh and but again importantly 86% of those rare desk being fully vaccinated were among those over 65. And so that really led to these um final recommendations for who need a third shot. I will reserve the topic of compromise but boosters are for over 65 years old, 18-64 with medical conditions immuno compromised patients and those with occupational exposures already told you that comparison data of Moderna versus Pfizer versus johnson johnson. I do think the johnson and johnson is going to need a second dose. Um And that will that meeting for the FDA to approve an E. U. A. For that um is later this month. Mhm. And then finally in terms of the state of the pandemic, you know um Covid delta is a very transmissible variants. It hit our country harder than many other countries who had higher rates of vaccination because Um we have a very mixed population and we had a lot of vaccine. We had we had about 70 million Americans by the time it hit that were eligible for vaccination but did not get the vaccine. And other places when delta variant hit um like Europe places in Europe had much higher rates of vaccination than we did when delta came and fared much better. Um what happened in our country as we had a very variegated response around the country, California was hit with a lot of pieces but the hospitalization stayed manageable because we did have relatively high rates of vaccination when delta hit. Um But places in multiple places in South and and around the country had a terrible um and hospitalizations because they had such low rates of vaccination among even eligible. So The US epidemic now it is coming down cases are down 30% um California actually it's so are hospitalizations which lag behind cases. But then they happened, they started to come down so are deaths. Um but it was it was a terrible price uh that we didn't need to have just given where other other countries were in their rates of vaccination. We had lower rates were about 45th in the world. We had fallen down to By Delta even though we had a high access to the vaccines. Um and uh and because it's such a transmissible variant, there's a lot of natural immunity as well as we did manage to get 38 million more people vaccinated since the beginning of delta. But between all of that the cases are coming down and California has the nation's lowest viral transmission rate. And so I'll end with the idea that our entire purpose of all of this is to get down there cases as low as possible. Of course we want. It would be nice if we could eliminate it. But I will tell you that that that Covid it's very hard to eliminated or eradicated, which means reducing it to zero in the country is elimination eradicated around the world because it looks so much like other respiratory viruses. Um But getting it down to control would be a wonderful top place to be. And you can see that something like smallpox which is the only disease except for a cattle related disease that we've eradicated was really distinctive. It could only be smallpox. Um But the problem with Covid looks like another lots of other respiratory viruses. It has a longer period of infectiousness, it can spread when you feel well and that's made it proven very hard to eliminate. Eradicated. But the more we get a new, the more will be in control like measles and pertussis and that's what we want to be more and more immunity to get to very low levels of control and some new treatments which are coming out that we monoclonal and a new antiviral that we can hope will help treat. So I'll end there and turn on my colleagues. All right, thanks so much Monica. That was excellent. And you can leave your summary on just for a moment. I remember to the participants for your questions into the Q and a box. We'd love to see them. I think a lot of the questions that have come up, you know, in terms of the health care providers and people who have forward facing jobs with patients is whether all dogs should get a booster. Um and if you got the moderna where there isn't a booster yet, should you? Is it just called re vaccination and not a booster, you know, what is the right terminology and what should health care providers do, you know? So, um if you're an immuno competent healthcare provider, I think it really depends on the degree of exposure that you're having. I would absolutely put someone who is exposed to immuno compromised patients, which we'll talk about next, which there would be more shedding or longer pit of shedding. I would put you in the category of meeting at booster, someone, a respiratory therapist, pulmonary doctor, someone who's very forward facing and can be exposed to a lot of covid patients. Um but someone who is sort of more distance from patients, it doesn't seem to be as urgent to get that right now. And certainly again it all depends on your circulating rates in your community. So we have quite low circulating rates in san Francisco at this point. Um So I think it's an individual decision for the health care provider and maybe between them and their provider. One thing I will say though is that ultimately speaking, I do think that johnson johnson will never be enough with one. Um There's only yellow fever vaccination that we've ever given one dose of the vaccine. And even then if you have a lot of exposure will give you another dose. So that's going to be a two dose vaccine and that's going to be reviewed later this month. Fighter ultimately could be a three dose vaccine though saying that all those all medical, all vaccines are three doses not accurate. There are some two dose vaccines and we do have some very good links, no data and no data that that that Memory B cells form for two doses. Um but the moderna which is holding up the best um is not yet approved for a booster. It will be 5 50 micrograms though when it's approved which is half the dose. So if you want to wait, I think you have time to wait. If you're not very forward facing. If you're very forward facing with patients, especially at a rate of high transmission. I would get the Pfizer vaccine right now. Their third dose that's really helpful. And another question I think that comes up. Um, these are really what the long term impact is of the pandemic. Obviously we don't know if another variant will show up but it hasn't yet that's had the same. I think trans missive Nous of Delta. But do you think that people will be getting vaccines annually? I mean there isn't much, I mean we got that smallpox and the little sugar when it came out. Those of us who are old enough to have been there when it got developed. But then we were never vaccinated again. Is it you mentioned how different it was from smallpox. So what happens with this? It's a great question because you know, there are vaccines like measles that we give as childhood and then we'll give them before pregnancy for example or like right before you go to medical school. So really again, depends on your exposure to a virus. If we could get transmission down worldwide, we wouldn't need frequent boosters and maybe in five or 10 years. And that's why I can. Global vaccine equity account think of anything more important because these vaccines have shown us and I'm not talking about the company's populations but immuno competent patients that they literally did limp no biopsies of people and you could see strong T cell memory T cell and memory B cells forming. So those are the kind of things that last a long time. There was this paper that I always refer to from influenza pandemic where they found 90 year old in the year 2000 and eight and they have been exposed in 1918 to the 1918 influenza pandemic 90 to 95 years later. These individuals still had strong memory Weisel immunity from 90 years ago and they exposed it to the virus to expose their blood to the virus in vitro. And they produce strong neutralizing antibodies to that 1918 strain that protected mice from exposures. So these memory B cells can last a very long time. Get immuno competent. So I think it could last a long time. But the reason we're going through this right now is we never got transmission down and not so I hope we can do that. I hope we can get vaccines to the world and get transmission down and absolutely won't keep on media boosters. And one other final thing I want to say about that is Delta has been around since March 4th. If you really look at the, what happened in India started then and it's been kind of the variant that rules them all at least for seven months and counting and nothing has been able to replace it. So I'm hoping Delta is the last one. But it depends on what we do. And then do you think? I mean I was talking to a patient today about needing to get a flu vaccine and who happens to be a health care provider and saying that, you know, it is amazing that last year no one got the flu. Um I mean no one and it's really interesting one. We've had really pushed for vaccinations which we have this year too. But wearing masks seems to have worked pretty well. Are we going to be wearing masks forever now? I think that will be a societal decision. I think that after the SARS pandemic in the late 2002 and the most, a lot of 2000 and three in many East asian countries there was a cultural mask wearing afterwards. But it was usually when people were ill. Um and not going to work. We just had I. D. Week last week and we decided that the best thing you can do instead of wearing a mask all the time forever is don't go to work when you're sick. And I do think that that is going to be a cultural shift that has to happen especially with healthcare workers. I doubt that americans will shift wearing masks. All the type of people can. But I don't think that that's going to be a shift in the United States. Yeah, I would agree with you. And of course I think it is the patients who come in who are sick to that creates some problems. I think with that. Well I thank you so much and hope you stay on for any Q. And A. That comes up and pass it over to your colleagues for tim and the other Monica. I think Monica Phung are you starting? I'm going to share my screen. Your two million are going during everybody sees. Yes, looks great. Right. Um Well I'll say on behalf of myself and Tim were very excited to talk about covid vaccination and immune responses and immuno compromised patients after Monica gave such a great background on just covid and vaccination in general. Okay, so I uh dr frank and I will will will tag team this presentation for you. So we'll be trading on and off as we go through slides. But I do want to say um and that was a phenomenal review by dr Gandhi. So I'm gonna actually go through uh don't need to cover vaccination in immune competent folks in much detail, but I did want to just show a slide showing that uh you know, as we are trying to learn more and more about long term immunity and how we measure that immunity and what that means. We can actually go back to natural infection where we have about a year and a half. Almost almost two years now coming up to in terms of looking at how immune responses may hold up over a longer period of time and again this is going to be different from vaccination, but one of the things that we did through our link study and in collaboration with a greenhouse lab and others was to look at at different essays that measure antibody responses or antibody neutralization capacity etc. And found that there was actually a wide range depending. So for example the end abbot of nuclear capsules essay that that was first reported and really first clinically available showed a rapid reduction in in in titles. But in reality when you look across other essays that look at different either episodes within the virus or whatnot, you actually see quite a bit of difference actually. You see a lot of stability over time. Uh yeah, except neutralizing antibody tigers also seem to decline initially within the first several months uh and then somewhat normalize over time. So I think this is just to show that although we we have when we're looking at graphs of immunity and antibody responses, it's going to be variable depending on how you look at this and what to do. Uh next slide please I won't go over this as dr Gandhi covered this in great detail but showing that there are many very efficacious vaccines that have very strong both uh antibody as well as t cell responses. Next side. Oh, that's good. No, this this is perfect. You can go ahead that uh that was already covered. I I do want to kind of pick up the stream about what about variants and and is this going to impact how the epidemic is going to look over time. And I think that I I also would love to have optimism and say that Delta is really the last the last barrier. That would be fantastic if it was um I guess, you know, but hopefully that will be the case. But I think that, you know, covid does evolve and whenever there is community transmission wherever it is across the world, that there's a risk of Covid 19 evolving and all like that. But there have been studies showing that covid 19 may evolve quicker and innovate immune responses more in our immuno compromised uh participants in patient population. And that's going to be very key key going forward to thinking about how we treat and vaccinate are immunocompromised folks. Uh there have been some similar studies showing that that various variants P one, the brazil strain, for example, initially from that region, but the P one strain, the et cetera may maybe less uh uh may evade vaccine responses more quickly when looking either at neutralization uh or binding of antibodies. But what's interesting with this, this study that was recently in science advances show that those that actually had natural infection actually had less protection cross variant than the vaccination. The vaccinated population itself. So that actually bodes well for vaccines overall. But I'm just hoping that vaccines don't emerge as dr Gandhi said when you appeared it was extremely short lived in the United States, it's almost gone now after it kind of first emerged, which although it does evade vaccine responses more easily is not as infectious as it seems as delta and that's a good thing overall. Next slide please. So I wanted to shift now just to the immuno compromised population. Uh this is actually quite different from our immuno competent person. So I think many of the studies that we see or read are really designed for people that are not immune suppressed and so many of these patients will not be cr I type patients as well. And I think some of the first data came from the solid organ transplant ah patients essentially. And what was first announced was showing that in response to vaccination, this is a similar article in Jama from the Boyarsky and Grusinsky wine group that there is essentially a lack of individuals who responded to vaccination both after the first and the second dose. And if you look at these at the binding site, the RBD side on the left and The S1 domain of spike on the right. It actually looks as though people are having robust antibody responses. But I think anything under 50 on the left graph is actually going to be not very protective. Uh and what they're finding is that actually only about 54% of this population, these are folks with uh for example, kidney transplant or liver transplant, heart transplant etcetera actually developed an antibody response in general. And we were certainly seeing an increase in immunocompromised folks that were vaccinated that we're seeing on service as well. Uh next slide please. Um So I just want to show you an example from our own study here at link. We're very interested in looking at vaccine responses and immunocompromised persons. We recently published a case report of discordant virus specific antibody levels and t cell responses following a third dose of SARS Kobe to vaccination. And someone with connective tissue disease on severe prolonged immunosuppressive therapy including uh riTUXimab so anti B cell therapies um uh as well. Uh And this was actually this is we we did this before all the data started to emerge. So it's you know one patient I realized but but I thought this this is a very informative case that what we saw was that uh this participant actually developed a detectable antibody response after the for two doses of MMR vaccine. But then after you know they weren't very high actually um uh comparatively. Uh And um what's interesting is even after a third dose those vaccine responses was started to wane and started to go down initially. Uh And that was cause for concern when we look at our healthy vaccine controls on the right looking at both neutralization and total antibodies, what we didn't see in this participant was any neutralizing capacity. So all the developed an antibody response. So they had a detectable total I G I G. M. S. A. Uh to the spike. Uh the RBD region in the spike protein. There was absolutely no neutralization that was was measured. And I think that this this gives us caution that, you know, and particularly the folks that have anti B cell therapy, that there may be severely impaired human responses. Even if you can detect antibodies. And that led us to think about how do we how do we deal with the immuno compromised patients that may have low level or modest levels of antibodies. Are they functional? Are they able to protect against primary infection or modulate disease severity? This participant was on anti cd 20 therapy. Um but before um uh so, you know, it's clearly had a reduction of the memory B cell compartment and the percent B cells was actually less than 1% before. After the first vaccine down below. However, when we looked at cd eight T cell responses, we actually saw an increase in cd eight T cell responses. I'm showing you either interfere on production or interferon and uh tumor necrosis factor alpha production interested really in Both CD four and CD eight T cells. And what we saw is that we stimulated these with um Essentially the same peptides that the vaccine elicits a response to. We saw that there was actually an increase in CD eight T cell um responses that were similar to healthy vaccine controls without um you know, compromise. I would also like to mention that there was a recent paper by john worries group that was fascinating. That showed that people that were getting took some ab for M. S. Had a severely impaired human neural response which is what we would expect from this data but also from other studies. But they had a paradoxical increase in the cd eight T cell frequent or the frequency of of of SARS cov two specific cd eight T cells. So the question was it was impairing human immunity but there was actually this This this compensatory perhaps uh increase in CD eight T cell response. But unfortunately this population is at more at risk of developing more severe disease and hospitalization. So the question then becomes what exactly is the C. D. A. The role of cd eight T cells or cd four T cells in that matter. All those are probably more related to antibody production and education of B cells within B cell follicles and lymph nodes. But you know I think it really brings up some questions that we really don't know what what What exactly is the role of CD eight T cells playing. I suspect that they have a beneficial effect on modulating disease but whether the protective against primary infection we actually don't know. So I think that that article was compelling and brings up a lot of questions that we need to dig into scientifically next slide and just to say that you know folks have started thinking about what to do in the email compromised population. Do you give boosters of M. RNA. Do you give boosters of a different vaccine like johnson and johnson if you've already had Moderna Pfizer or vice versa or do you reduce immune suppression? Do you hold him in a suppression? And these are all things that obviously people are trying and studying now, especially boosting. And I'll show data for that later after Dr Fung talks. But one thing I do want to mention um uh is that you know, in the setting of holding him in a suppression that we have noticed in some of our link participants that even if they stop riTUXimab six months before vaccine, there was still an impaired vaccine response. And I think that that's important to keep in mind when thinking about the cancer population. Next time I'll be talking a little bit about cancer patients in particular in vaccine response. Um so this is a study that looked at 151 cancer patients versus 54 healthy controls among the cancer patients, 63% of solid tumor, 37% had he malignancy. And and all of the participants received two doses of the Pfizer mmr vaccine. Um some at the standard 21 days apart which is the data that is presented and then some actually received a delayed 12 week boost. This is a european study. The data was not reported in the paper. And so what you see is that healthy controls, as we know from all of the large RCT is the amount a great moral and t. Cell response after the first and then 100% after the second does. But there is a decrease response in both solid cancer. But even more so in key Melinda MSI patients. Um you can see for a solid cancer patients after the first dose. Only about 40% had an IgG response. Um uh And then that went up to about 95%. Which is pretty good after the second dose. Whereas human tendency was much lower 18% after the first dose, 60% after the second. Is that these um These results are kind of mirrored and um kind of the T. Cell response. And so of course everything when it comes to vaccine response we care about I. G. S. But more importantly about mutualization tigers. And what was important is that compared to healthy controls. Solid cancer patients actually had pretty similar neutralization tigers whereas there was a decreased neutralizes fighters and humility. So breaking down these groups a little bit more. So this is a study looking at a just solid tumor patients. 102 of them. Compared to 78 healthy controls who received two doses of Pfizer vaccine and you can see the breakdown of the solid two years here. Um What's good is that kind of similar to the prior paper, 90% of the cancer patients were positive after the second dose. Um But the median I. D. G. E. Tigers whether whether or not we know what to make of those were lower than the control and that the big the risk factors associated with lower antibody tighter we're receiving chemotherapy and immunotherapy. Um So this is a study looking specifically at human malignancy. This is a registry trial where they looked at close to 1500 humility patients who received two doses of either of the Madonna or Fighter M. RNA vaccine. Um This show that 75% had a positive anti spike antibody. Um And there were higher responses with Moderna than Fighter which we know we just talked about home with your in a hell is it's a better I mean potentially due to the never. Um the lowest rates of anti body responses were in all kind of subtypes of non hodgkin lymphoma ranging from 20% to 56% cll patients. About a third of them have an antibody response. Um And um car T cell therapy. Um And they were actually pretty high. I apologize. This is this is a type of their style lower. Um Actually amL amL CML patients and Hodgkin lymphoma patients actually had pretty high positive antibody responses. So of course he malignancy as you all know is not they aren't all just one bucket um stuff are different. And what about stem cell transplant recipients? Um In this study of 88 stem cell transplant recipients who received two doses of the Pfizer. About the median of 23 3 months was transplant. Um 78% have to quantify a little anti body, 18% had no detectable antibody. And there are higher responses in patients who are greater than one year post transplant. And what higher absolute lymphocyte count. And of course on the opposite side, lower responses on among those who are still on immuno suppressive medic. And so I think this is a great slide that was presented at the cbc advisory committee that actually compares the cancer patients to the other immuno suppressed patients. And you can see here cancer is this column um light blue is our solid tumor patients and then dark blue or the humility. And you can see that there is decreased response particularly. Okay then why do we care? Of course a doctor dot he did a great job of outlining this. We care because of breakthrough infections about the vaccine response. And so this is just an example of the study um from Israel that showed that among hospitalized patients with breakthrough uh Covid 1925% of them were cancer patients and cancer patients made up 32% of patients with poor outcomes. And then actually low tide waters of anti spike I.g. were associated. So the current vaccine strategies for cancer patients is we want as many of them as possible to get vaccinated. Um Once they are vaccinated. Um There I think it's important to clarify the concept of additional dose or third dose versus the booster dose dr Gandhi spoke about this. Um But the point of the additional or third dose is for patients who did not amount to sufficient response to the initial vaccine series to actually improve their immune response. And so when this most approved a few months ago, the criteria were patients who were on active treatment for solid tumor malignancy, who had received uh some salt transit. And these were patients were we've gotten M. RNA series greater than 28 days before and then you get them a third. But the newer recommendations are about booster dose and the goal in this situation is actually different. It is to actually reduce covid acquisition and disease severity among patients who we know are at higher risk for getting subdued. And so this is where the third dose of the fighter is coming in. It's for older patients and anybody with kind of medical conditions including. Um And then I'll just we'll touch a little bit about kind of future in additional prevention strategies. This includes vaccination with starter Henrich, we'll talk about passive immunotherapy with monoclonal is and then we're all very excited about the new um some new antivirals. I've just had a promising data. Oh perfect. So so you know it's interesting that as we talk about boosting but I agree with dr fung and it's it's really not boosting in this population. It's continuing to vaccinate until you achieve a response. We do this for other vaccines as well. Hepatitis B for example. This is not this is not you know alone in terms of covid in terms of those that are compromised. And I think there's now data just starting to emerge on using more than three doses. So not boosting per se but giving 1/4 dose in our immuno compromised patients that don't have adequate responses to the first three doses. So if the first two didn't work, why not give a third? Uh And johns Hopkins group on the left. I apologize about the tiny table there, it's hard to read but an accepted manuscript showing that actually a not insignificant number of patients that lacked or had a modest response after the third dose actually responded to 1/4 dose. Uh And there's also a recent group from europe now showing that in those that did not respond after a third dose about 50% or 40 to 50% or so actually achieved higher levels of of antibody tigers after 1/4 dose. And again these are in solid organ transplant participants and patients. So a little bit different and tend to be more even a suppressed. Uh Apparently for the first two doses. But I think the question is why not we why don't we just keep going until someone has an adequate response. Uh since we do it with with other diseases. So it's a question that's now starting to be asked and maybe an answer will be here with us soon. Um and then as uh kind of piggybacking on what dr Henrich mentioned, we also want to know kind of watch vaccine we want to give as additional doses. There's going to be some increased some new data that's coming out pretty soon on a hetero ologists um covid vaccines and then you know, comprehend patients. But this is just an example in immunocompromised patient um with lymphoblastic lymphoma who is treated with riTUXimab routine. And there's an en route nib who got two doses of the Pfizer vaccine didn't have a detectable antibody response. And then actually then got the J and J 10 weeks later and then had an antibody response which was confirmed by anti body. So this may be one of the techniques sure that we have to increase our patients. And then I also mentioned passive immunotherapy monoclonal antibodies as a preventative strategy. Um Right now it is approved for post exposure prophylaxis um for patients who are not fully vaccinated or vaccinated but not expected to mount an adequate immune response. So our immune compromised patients and if they had a recent close contact or in a high risk chronic setting. So in a nursing home residing in a prison or in um we've also we've been using the criteria of and then what we're really hoping to see is what to do um for pre exposure for blacks as in the other underway. Um soft. Okay. And I'll just finish briefly uh Yeah, I think everybody's been watching the news about uh multiple revere as a potential treatment for early disease to avoid hospitalization and death. And obviously this was big news for markets all by news releases, how we get all of our uh initial covid data now anyways in the scientific community, which is interesting. But basically this is an oral drug that can be used twice a day That showed a 50% reduction in death or hospitalization uh in those usually fairly early in disease. Although they didn't see any differences in efficacy by timing of symptom onset variant or risk factors. But it was a relatively small study and folks were fairly early in the course of disease. I don't I don't really know what to make stock of this until I actually see the data which we haven't seen. But I do want to give you a fact that although this is a potential promising strategy for our cancer population, especially in early disease, very much like a monoclonal antibody therapy maybe as well is that this is this is a nucleoside analog. So it's a it's a side of an analog but it's not like the nucleoside or nucleotide analog we use for HIV which insert themselves in this case in the RNA dependent RNA polymerase chain elongation but rather than a boarding this like we would in reverse transcriptase inhibitors. Uh this actually gets incorporated into the R. N. A. And over time increases the muted genesis uh of the virus and actually leads to viral viral genome which is RNA. So RNA genome mutations that are detrimental to the virus. And there's actually been some in vitro data showing that there may be also mutagenic potential and integration potential in mammalian cells from this from this analog as well. Although again we haven't seen any data so it's hard to tell. But there have now been some prominent scientists who have worked on the initial nucleoside and nucleotide reverse transcriptase inhibitors for HIV that are expressing some potential concern that there could be uh potential neurogenesis risk of a million cells. But again, I have no data to support plus or minus but but this is something just to look out for when thinking about some of these novel therapies with evaluating them without without without data in hand. Great, thank you so much. That was really a fabulous uh you know, handoff back and forth. Really great and I learned a lot. I think that it's really helpful for our audience and for those who listen to this later. We have just time for a couple of questions to ask. But one of the questions is you know, we see how the status with anybody's should we be uh measuring anybody's is there a quick response to that. Uh so the transplanted group as dr fung knows, we we discussed this every week and we have never come up with a firm consensus on what to actually do. I think you know the and all the doctor can speak to this as well. But you know the thought is you know that we see, you know, what should we be testing or should we just be giving more doses or should we be treating folks Is that they're not going to have an inherent immune response uh in this situation? And I don't think we we don't have a prospective data to answer that question I think is the problem. But you know clearly if if you have a modest or or negative antibody response in the setting of immuno suppressed immune suppression, you don't compromise that that's going to bode poorly for the for the patient. It may be measuring the spike protein antibodies rather than the nuclear cap said. I mean I know I wanted I forget why but I had some blood tests for government. It was the wrong one which was negative actually. I've been vaccinated but I don't think it helps you so much if you had the nuclear caps it. No, no, they're vaccinated. So that's the problem. And so people can get misled. Right right. And you can you can there's a send out you can do for the spike antibodies, you just have to specify. It oftentimes will suggest. But then they'll send the wrong ones. Yeah it depends what you're looking at as well. If you're not looking at a vaccine response, which nuclear capsule response will not show. Uh then then you just have to realize what you're doing. So this is complicated but I'll Monica, Monica dandy. Do you have a any thought about that? You know? I think the minute they would know, I mean I will say that I treat only people living with HIV and uh we have resisted sending out of bodies because it is really confusing for people and they could still have responses from their T cells. And um so so uh more in the research setting. Um and we haven't been letting people boost with antibodies. So I think the answer to that is it's still a little bit unclear whether these blood tests really help our patients. And then another question is that uh you know, we have solid tumor patients who are being treated with hormones, radiation and surgery but they're not getting chemo or steroids, they seem to be have relatively robust immune responses. I don't think they really fit into our immune compromised patient population. But we all have patients who don't want to be vaccinated and then get covid should they then get vaccinated, are we telling them to is what's the advantage to them since they have great mistrust against vaccinations. Absolutely get vaccinated. So we know there is recent data from the Rockefeller from Michelle nuisance wags group who developed a lot of the monoclonal broadly neutralizing animals to treat HIV that in certain number of patients who were previously infected and then vaccinated they can actually develop extremely broad antibody uh kind of repertoire that is far better than either vaccine alone or natural infection alone. It's not everybody, but it's a certain small number of patients but I'll pass it to others. Absolutely. There's there's great clinical evidence that getting vaccinated after having an infection still protects against future infection. Um and I will say on the anti spike topic uh we are still debating on what to do with it. But I do think it's the wave of the future right, the recovery trial that came out for using monoclonal antibodies for patients who get admitted require people have a negative anti spike. And so it's going to be kind of incorporated into I think are that's really interesting. And I think um it is also a question about whether or not you recommend that somebody get Pfizer or Moderna now um because maybe one has a better uh you know, protection duration. You know, we I will say that we did a study with TIM as well where we looked at patients with HIV who got Moderna versus Fighter and saw the same sort of um finding that was in a jam a paper of non people not living with HIV that the antibodies were higher with Moderna than fighter and again I think it is the higher dose but I also think four weeks it was just a better duration than three weeks. So that was probably too short. They were trying to do the clinical trials quickly. So um for a booster it doesn't matter anyway because it's six months after your second dose. But I do think the Moderna has some advantages as an initial um vaccine in terms of what that data we saw in terms of protection. That's great. I really appreciate that and I very much appreciate all of your discussions and talks. This was really fabulous and it's great that we're able to record it also so that it can be seen by an even broader audience. So thank you so much for your participation this evening and we'll look forward to continuing to talk about the covid pandemic with you as things progress. And now it's my pleasure to introduce Donald Abrams who will talk to us about Integrative Oncology and then we'll have a little time for questions at the end. I and just to keep in mind that in the chat box I put a link to where the recording will be afterwards. Um and we will also be having additional sessions throughout the cancer center Grand rounds series and the next one will be I think a really interesting update on breast cancer from the san Antonio breast cancer symposium exercising cancer and a little bit about the ice by you know, a german program. Donald. All right, thank you hope. But everybody take a deep breath and close your eyes and then open them just to get us into a different space. So, I am going to talk about integrative cancer care. I do have some disclosures as shown here and what is integrative cancer care. I think this quote which is often attributed to William Osler really goes back to my monitor is a hebrew sage. It is more important to know what sort of patient has a disease than what disease a patient has. And this was recently reiterated in Asko Post, which is my sort of what I read to keep up to date the patient we see in the person we may not, although we treat the patient in front of us proficiently, we sometimes can be oblivious to the person behind the patient while the patient carries the diagnosis. It is the person within who carries the patient. This becomes important because it is a person and the vicissitudes of his or her life that determine the patient's presence, absence and behavior. To put it another way I always said, when I was at SAn Francisco General, I treat cancer and at the Ocean Center for Integrative Medicine, I treat people living with cancer. So I define integrative cancer care as the rational evidence informed combination of conventional therapy with complementary interventions into an individualist therapeutic regimen that addresses the whole person body mind and spirit with cancer. And you'll notice italics sighs informed because we as oncologists are the most evidence demanding I think of clinical specialists because we deal with a very serious illness and we use very potent medications. So we like to see randomized control clinical trials in the literature before we make recommendations to our patients. However much of what we do and integrated oncology is really more evidence informed because it's difficult to do a randomized placebo controlled trial of blueberries, broccoli massage or even acupuncture. So integrative Oncology provides relationship centered care. I used to start my new patient visit by saying, tell me your story. But my my price Gainey or whatever that score is my score for doctor knew my history was the lowest of all my scores. So now I tell the patients their story, but In asking them to tell me their story and not interrupting them, as most physicians do. After 17 seconds of speaking, I begin to establish some sort of a relationship. Integrative oncology integrates conventional and complementary methods of treatment and prevention, aiming to activate the body's innate healing response using natural, less invasive interventions whenever possible. Integrative oncology engages mind, body spirit and community. Rarely do. I see a patient coming to see me resuming with me alone, more zooming alone than visiting. But because cancer does not just infect infect the individual, it infects their whole community. And Integrative oncology encourages providers to model healthy lifestyles for their patients even though it's against OSHA. When I used to see patients live, I would be drinking my green tea during my morning clinics. Integrative oncology focuses attention on lifestyle choices for disease prevention and maintenance of health and maintains the healing is always possible even when curing is not. So who do I see in consultation at the Ocean Center? Very rarely do I see patients who are seeking alternatives to conventional cancer therapy. The so called refuse mix. I think about 5% of patients I see are in that category and I usually wind up referring them to one of my colleagues at the cancer center after trying to convince them that I have no alternative options. More commonly, I see people seeking complementary therapies while undergoing conventional therapy to either mitigate the symptoms of their cancer, its treatment or to hopefully help prolong their remission. The other group that I mainly see are those seeking optimal survivorship care. There are a few people that I see at the other end of the spectrum where they've run out of every treatment that we have available in conventional oncology seeking some sort of miracle cure, which I don't have breeze belle is an integrative palliative care specialist who has really taken over seeing the integrative end of life care patients. So what are my goals of an integrative oncology consultation No one. And I think really most important is to increase the patient's sense of control when you hear you have cancer immediately. Your locus of control has been ripped from underneath you. We're now at the mercy of the surgeon, the radiation oncologists, medical oncologists and even the chemotherapy nurse, decreasing ongoing inflammation is something we now appreciate inflammation as a cause of many of the degenerative diseases of aging, dementia, heart disease and cancer to some extent. Another goal is then by decreasing inflammation. We help unload the body's own immune system in the fight against cancer uh similar but not quite as expensive as what we're doing with our checkpoint inhibitors. When I did ask patients to tell me their story, they often wove a story as if stress caused their cancer. I don't think stress in and of itself causes cancer but stress is not good for cancer or anything else for that matter stresses adrenaline decided toxic and cortisol uh steroid hormone which is an immune suppressive and then off these things together I think serve to increase the patient's sense of hope that they are doing something themselves. So how do we increase that sense of control by controlling weight. And as you know, two thirds of America and now overweight or obese and controlling weight is by altering diet increasing physical activity. We then discuss appropriate use of supplements and the breath, I asked you to take a deep breath to sort of punctuate where we were and where we are and the breath is sort of a link between the mind and the body because before I mentioned breathing. We're all breathing, autonomic li and now we do appreciate that. We can control the rate the onset and the depth of our duration of our breathing. And that is sort of the link between much of a people do for mind, body interventions, hypnosis, yoga is moving with your breath, a guided imagery for people that need a little bit more than just their breath is very useful. And I ask patients to connect with their family and friends and engage in their religious beliefs or their spirituality With regards to the first three uh control issues that I discussed. I rely heavily on the American Institute for Cancer Research, World Cancer Research Fund recommendations for cancer prevention, but number 10 is for after a cancer diagnosis. Follow the nine guidelines above and again, number one is to be a healthy weight and you can do that by being physically active. Number three is the first that says anything about food. And it used to say avoid sugary drinks, which I think is better than sugar sweetened drinks because data from europe suggests that those people who only drink fruit juices also have a 14% increased risk of developing cancer, limit consumption of red and processed meats used to say limit consumption of red meat and avoid processed meat, which I again believe was more correct because processed meats are considered a class one carcinogen by the World Health Organization. The positive recommendation is to eat a diet rich in whole grains, vegetables, fruits and beans and then one more negative is to limit alcohol in the past. The guidelines said if consumed at all limit to two a day for men and one a day for women That was in 2007. They changed it when they updated the guideline in 2018 to save for cancer prevention, it's best not to drink alcohol. And this year they also shouted out fast foods and other processed foods high in fat starches or sugars as one of the means by which we've become an overweight and obese society. So I believe the ideal diet that I discussed with patients is organic, plant based antioxidant rich whole foods. So many patients I see say I have cancer, I'm going to juice everything or I have cancer, I'm going to Sprinkle broccoli powder in a smoothie. I think it's always better to eat whole foods and this diet I believe is anti inflammatory. It's important to appreciate that in this Jama article on the state of U. S. Health 1990 to 2016 burden of disease. They suggest that the number one cause of death in the United States today is dietary risks and that exceeds tobacco and high blood pressure and doesn't include high body mass index or low physical activity. So if you add those three lifestyle parameters together, it's off the chart. That article didn't tell us what the 14 components of dietary risk are. We had to go to the lance at an earlier article said that diets that are low in fruits and vegetables, whole grains, nuts and seeds, milk, fiber, calcium, seafood, omega three fatty acids and polyunsaturated fatty acids and diets that are high in red meat, processed meat, sugar, sweetened beverages, trans fatty acids and sodium. So many people for some reason feel that I'm a vegan and I am not a vegan actually. And I don't think vegan is a particularly healthy lifestyle. There's no culture that's had vegan as their diet that's persisted. 7th Day Adventists are usually some sort of a vegetarian And this is an article from Jama Internal Medicine a few years back. Looking at the development of colorectal cancer in various adventists studying 77,000 people They found that when adjust the hazard ratio for colorectal cancer in vegetarians versus non vegetarians was a 22% reduction vegans interestingly only had a 16% reduction. Pesca Terrians, Pesca vegetarians, those who also eat fish have the greatest 43% reduction in their risk of colorectal cancer. This is an article from walter Willet who's harvard's best nutrition. Uh investigators scientists and it's an article on dairy that appeared in the new England Journal of Medicine last year and I share this with my patients because suddenly in the middle of this article on dairy, he has this graph of all cause mortality associated with protein sources and the dotted line for reference is dairy and below dairies, plants, poultry and fish and above dairy is red meat, eggs significantly above and processed meats off the chart. So the guideline to limit consumption of red and avoid processed meats I think is the best guideline. So what I discuss with patients in the 1st 20 minutes of my consultation is food recommendations and our nutrition colleagues at the cancer center are absolutely fabulous. I love great um a carrie and her recommendations and the program that they're doing starting tomorrow for our patients on eat to nourish. But I'll tell you Our patients really like hearing an oncologist say something other than it doesn't really matter, eat whatever you want because it does matter. And when an oncologist talks to a patient for 20 minutes about food, I think it's a motivator to make change. And I'm very appreciative when patients tell me how much better they feel after changing their diet and lifestyle. So I recommend that patients increased their plant based foods, particularly heavily pigmented fruits and cruciferous vegetables, flowers grow in the shape of a crucifix, increase whole grains, decreased animal fats by eliminating dairy, red and processed meats or minimizing poultry, preferably organic because otherwise it's highly inflammatory and increased marine omega three fatty acids, decrease refined carbohydrates sugar. White flour, white rice, jasmine and basmati are better than Uncle Ben's or sushi rice seasoned with ginger, garlic, onions and turmeric. And if you're beverages, think about christmas, green and red green tea and red wine. If any alcohol at all is probably the best beverage. Now the standard American diet is not as good as what the Institute of Medicine recommends. As far as macro nutrient displayed, they recommend that the diet should be about 60% carbohydrates, 20% protein and 20% fat. Standard american diet is excessive in fat, decreased in protein and carbohydrates. Many of our cancer patients want to consume a ketogenic diet. I believe perhaps the most unhealthy diet out there. All fat and protein, macrobiotic and vegan diets are a little accentuated in the carbohydrates with decreased protein. Which can become a problem in vegans and probably not enough fat to make hormones which some of us actually need. Doesn't make any difference. Does it really work? Well, 41,000 people participated in a study looking at whether adherence particularly to the World Cancer Research Fund, american Institute for Cancer research guidelines made any difference and a one point increase in the score. I. E better adherence Led to a 12% decrease in the overall risk of cancer. 14% decrease in breast, 12 decrease in prostate and a not statistically significant increase in colorectal cancer. But pretty close. What about after a cancer diagnosis? Does it really matter? Well this is from an old study done by Jeffrey Maier heart at the dana Farber. Looking at nutrition in patients participating in A. C. A. L. G. B. Study of a given chemotherapy for patients with colon cancer. And he divided the group into quintiles of western dietary pattern that they consumed. And the group that consumed the lowest quintile on the left was the reference group. And as you can see as a diet became more western, the risk of developing recurrence increased threefold and the risk of death increased twofold. So just to show you this group on the right had one serving of red meat a day, five refined grains and too sugary desserts. Whereas the group on the left for reference had red meat twice a week, uh Too refined grains a day and sugary desserts three times a week. So it does seem to make a difference. And in fact the Meyer hard data was reanalyzed recently looking at what they called the food insulin index and they find foods with a high food insulin index evoke a stronger plasma insulin response. And so they calculated the dietary insulin load from the fruit frequency questionnaire and this food insulin index. And they found that higher dietary insulin load was associated with worse disease free survival. Both uh recurrence free and overall survival as well. And this association was independent of the western versus prudent dietary pattern from the chart that I just showed you. And the magnitude of this association was highest in obese patients. Well what about exercise? I think all of us are aware that exercise decreases the risk of a number of our most common cancers, breast colorectal and prostate, to name a few. This looks at exercise in cancer survivors. A meta analysis of 50,000 survivors. 16 studies and breasts and seven colorectal. The most active breast cancer survivors and the most physically active colorectal cancer survivors had lower rates of death, both from their cancer and all cause mortality. And interestingly, survivors who reported an increase in activity only after their cancer diagnosis also decrease their risk of death 40%, which is not insignificant. What about the oncologist now, I as somebody who used to see patients at the general in 15 to 20 minutes and worry about how they were doing on their chemo. Didn't really talk to my patients that much about doing physical activity. But this was a study looking at non small cell cancer patients, most of them desired advice about physical activity. From a face to face recommendation from their physician, 92%, preferring that if it were coming from their oncologists. A survey of Canadian oncologist showed that two thirds agreed that physical activity was safe and beneficial. Less than half ever recommended it and only a quarter within the past month when an oncologist recommends an increase in physical activity to a pick cancer patient, It results in an increase of 60 minutes of vigorous walking equivalent a week, which definitely leads to increase survival. And then recently a paper published looked at the different benefits of aerobic versus resistant versus a combination of aerobic plus resistance exercise personally I started doing my yoga practice late in life at age 60 but I feel that yoga provides strength, flexibility and balance. And then also if you're moving with your breath for an hour you sort of forget to think about everything else that's going on and during the pandemic, when I don't have a gym to go to, there were times early on when I did six hours of yoga a week and I think it's really important and something that has been demonstrated in many cancer sub populations to be of benefit. One of the other questions that I very commonly get from patients who bring me a shopping bag of supplements is doc can I take this? And I just want to point out levels of evidence that our patients use in deciding which complementary therapies are going to take. This was a survey of 38, men with prostate cancer in the United Kingdom. And when they were asked to rank what form of evidence they felt were most personally reasonable, meaningful. They ranked number one personal stories of people helped by the treatment today. Actually my new patient was drinking borax because his brother and sister in law said it worked for their auto immune diseases. I said I don't think you should do that. Number five for these patients was scientific evidence. So it's important for us to appreciate that the hierarchy that our patients used is somewhat different from ours. So Donald, I'm so sorry to interrupt you, but we're 20 minutes in in just at seven. So I'm wondering if you can wrap up a little just so we can have one question. Okay, so the reason, yeah I'll zoom patients are asked the asking really if there is a potential cytochrome P 4 50 interaction between the botanical they're taking and their anti cancer agents. And these can happen. And the other question that patients are asking is am I taking an antioxidant that's going to interfere with either my chemotherapy. That's working by oxidation or my radiation therapy which is uh working also by developing free radicals. So these are the supplements that I generally recommend to all patients more or less. I the only blood tests I order on patients is a 25 hydroxy vitamin D. Level because low vitamin D. Puts people at greater risk of cancer and people with cancer whose vitamin D. Levels are low, don't do as well as those who are normal. And then cannabis is another intervention that you all know, I'm very fond of, particularly for symptom management. There is a growing belief out there in the internet and social media community that cannabis cures cancer cannabis. There is no evidence in the medical literature that it does. But a recent article just published this year In 21 patients with glioblastoma. Multiforme me looking at a whole plant extract of cannabis with a 1-1 ratio of THC tetrahydrocannabinol to CBD did show that in this very small study, although two thirds of each group progressed at six months, the groups receiving the 1 to 1 ratio of THC to CBD had a one year survival of 83% compared to 44% which was statistically significant. Although this early phase trial was not powered for survival. So in conclusion, almost mind body interventions or what we recommend for decreasing stress, participating in support groups, journaling guided imagery, hypnosis, breathwork and we offer mindfulness based stress reduction course is at the cancer center as well as at the Ocean Center an acupuncture. I find my patients who are getting acupuncture in conjunction with their conventional chemo radiation, hormonal or immunotherapy do much better than those who don't. The NIH had a consensus conference in 1997 that said acupuncture was an effective anti semetic during chemotherapy. I wish my head neck patients would all get acupuncture prior to radiation to preserve their salivary flow. This is just a recent study again that showed, in fact, I think donald I'm going to have to okay, there it is. Past due group visits to And I ask patients three closing questions and the role of the physician is secure. So yeah. Okay, thank you. I so appreciate your excellent talk and it's just great guidelines for managing patients and I think you know, one question which you can maybe type into the Q. And A box because we're going to have to close you with increasing the sense of control and what kind of language you use with patients when discussing this concept. So if you could answer that typing in it would be wonderful. And we really appreciate all of our speakers this evening. Uh and your attention the audience. We will have this as a video posted on the cancer center's website. As I put into the chat. I and we look forward to seeing you at the next cancer center grand rounds where we'll talk about the newest developments in breast cancer. And also we'll be talking about new directions in Neo Adjuvant therapy And I am sorry that we had to we had 20 minutes really for each session. So I know we could spend the entire session talking about integrative medicine but never fear. Donald is fabulous and excellent speaker and I know that he will come back and join us again. We also will have him speak at our breast cancer forum. So there will be many opportunities to hear Donald talk again about Integrative Oncology and how we really deal with this in our oncology patients. So thank you very much