Ash Alizadeh: A New Age in Oncology
You. Today. On the future of everything, the future of cancer diagnosis. And treatment, well. I don't think I even need to say that cancer is a terrible, and scary disease. Or really, a set of diseases that affect many people worldwide, loved. Ones friends and people themselves, have. To struggle very few people are not affected, by this disease and recently. There's been great progress, and. And generation, of hope for improved, diagnosis, and treatment of cancer based. On really, progress in many areas. Improved. Imaging, methods. That take pictures and detect the cancer ability. To sequence the DNA of, the cancer cells to understand, exactly what's, wrong and what might, need to be fixed better, medications. That are focused on specific defects, in these, cells to. Give, a more, focused. Treatment. Improvements. In radiation therapy and, many, other areas of the US government, the, National Institutes of Health has, created, a cancer, moonshot, which. Is a large well funded research program, to accelerate. Progress in cancer research, in. The development of treatments and diagnostics, now. An important, trend in cancer. Research is personalized. Medicine, and what do I mean by that well, can, we use information about the individual, patients, to, more sensitively, detect the, cancer in the first place can. We use information about how the patient, responds, over, time to. Choose the right sequence of treatments and combinations, can. We help the patient understand, the likely, outcomes, of their treatment so they have less uncertainty, one, of the big scary things about cancer, is not just the diagnosis, but all the uncertainty, that that brings to the patient in terms of what, does that mean for my health and my life am i talking months years, decades what's. Going on dr.. Ash Ali's, Etta is a professor, of medicine and oncology. At Stanford. University, his, lab has focused on understanding the biology of cancer how it begins grows, and how you can treat it from, multiple perspectives, including, the transition, from normal, cell to cancer cell the role of the immune system and the creation. New tools to study cancer ash. One. Area you have focused on recently is. Forecasting. How, a cancer, will progress over time is it aggressive, will it respond to treatment, how should we monitor, it how frequently should we monitor it why, have you focused on this and what, could be the benefits, to patients and their physicians that's. A thank, you, Russ, so in. Addition to the things you talked about I happen to be an oncologist and, take care of some of these folks and, in large part. Focusing. On this problems been motivated. By the personal experience of looking, in the patient's, eyes. And, having a conversation with them as they go through this. Journey, that, you're going through with them and it's. A really, sobering. To look, at how blunt our tools are for. Getting. A sense for whether you're making progress as you're going through the course of therapy so the disease. I take care of clinically, is one of the most common, blood cancers, a aggressive. Lymphoma that we cure in, the majority of patients but, it's not a hundred percent and. In. Having a conversation with the patient about. The. Likelihood, of being in one of those, and. The group that is cured as opposed to the group that isn't, is. Something, that takes months, if not years to, determine. So. In all that time you and the patient are extremely, worried exactly. And so the thought was. You. Know we've historically, you. Know in, the past looked. At various. Time. Points during this journey and said, what information, do we have and. What. How, can that information help predict the future but. You. Know in in, part motivated by, seeing, how. Statisticians. And, other. Folks were making such forward. Progress using, statistical. Tools to look at dynamic. Data. In. Particular in relation elections. Nate Silver and. Some others to take longitudinal. Data and build, a framework. For saying. Who's gonna win this election who's. Gonna win this baseball, match who's gonna win this, ball game are, you smarter as you integrate information, over.
A, Time, frame when you're looking at let's say a version, of a film as opposed to still shots during, during. The transition, now certainly I'm sure doctors, and you yourself, in your practice over the years have tried to do this so what has changed, that, makes you, optimistic. That you can do an even better job right, so, yeah I had the, same thoughts but I don't think we, have ever really. Done this in a. Longitudinally. Integrated. Statistical. Framework that. Makes. An accurate, forecast, and I think even in my own practice, and. In. Chatting, with most of my peers, we almost treat the most recent, data as, the. Best data. So. What's the score at halftime as a best predictor, of the game forgetting. That maybe. Even quarterbacks. Out even, though the score is tied the, you know that he was injured on the last play, exactly. If you didn't watch the first half and you just tuned in a half time you. Probably, in. Assuming, that the score halftime is more important than having watch the first half you. Would be less, likely to make, a good prediction and so we we set out to answer this question if you integrate the. Information over time using a couple statistical, frameworks. Do. We do better um and. I surprised, actually because, I, set, out the guys to prove me wrong that. I that the most recent information would be the best information and. It. Happens, it seems to be true that in, integrating, information dynamically. You make a much better forecast. So can you how, does this actually work for. Real patients and real data today are they coming I'm sure they're not coming to the hospital every day for a measurement right there must be some sense of sure longitudinally, following, the monitor, so. We've done this now for three types of cancers, and are working on a bunch more but, we took the the most common, than FOMA which. Is large b-cell lymphoma. That's, the the, most common, blood. Cancer, we also took the most common leukemia, chronic lymphocytic leukemia and, worked the European.
Cooperative. Group that had collected large, numbers, of patients and longitudinal, measurements, and we took early stage breast cancer and, we, said okay there, are established. Still. Shots in the film that, have been defined as predicting, risk, stage, of the disease age of the patient. Burden. Of disease etc and, then still, shots as. Their. Response to the patient drop. Or have the pathology clear, or etc. But. Now we are going to staple, this information, together in, a statistical, framework that, says okay, I'll either consider these things in isolation or I'll roll them up into an equation to, give you a number and, that. Number will, make the forecast. Calibrated. Probability. So. If I'm understanding in, the, olden days yes, you might get two patients who had come to there let's say it's their two year appointment, sure and they look identical they, have a similar blood tests they have similar, imaging, that you can't detect the disease perhaps and in, those days in the olden days you might say these patients are essentially equivalent exactly. And then what I'm hearing you say now is the path by which they got to that point might, actually make them have different. Expected. Futures that's right so you might say you two looked the same but I'm gonna, smoke just to sound harsh I'm gonna give you good news and I'm gonna give you bad news because, the history of how you got here is very different exactly. So. So this path dependence. So if, you start and looking, exactly the same way you know you have the same risk factor Stage two it is easier a certain age and you, get the same treatment and one, patient has a response, one doesn't, of course that information is different and then you staple that information, forward and and. You. Make a prediction or you. Get to the same point that you know the score is tied but. You had prior histories, so. This is the future of everything I'm Russ Altman I'm speaking with dr. ash ELISA about. Cancer, and new ways to follow it and prognosticate. About it so. Is. This a purely research, result, or has it started to change practice. And in what and in what ways you, know since. The, paper is published as a theoretical article. And. I. Was, surprised by how much excitement. We've. Gotten from the community artists.
Our Collaborators, in Europe and the. Broader community of, American. Oncologists, about trying to take this framework and now that we've done it and several, diseases to. Use it for a predictive. Therapeutic. Change. Idea, we're still in the midst of designing, a good clinical trial where we take the information and say okay, now we're going to be changing. Treatment based on a number not. Based on a. Feeling. That feeling or let's say an image say, right a picture. Of here's, this much disease I have and, that, doesn't, have a whole lot of history so we've got to be careful about how to do. That right so that, we, have the best chance of having. The. Result means something, where, they're surprising. Results, in terms of as you looked at this data not only the current data but all the past data are their sources of data that we're surprisingly, more useful, than expected, or less useful than expected, or did, it actually play out mostly how you would expect in terms of what the most valuable pieces of information are, you know I, don't. Think I, think I was surprised, by how well the data complemented. Each other I don't think I would that I have a bias of course I've my lab has, spent. A lot of effort on trying to develop non-invasive. Diagnostics. Liquid. Biopsies, for. Helping. Make, these movies, right to get a sense of what's happened and for those who are not familiar the liquid biopsies, are samples. Of blood where you can detect the cancer. Or cancer and so it's much less invasive than a biopsy or a surgery that's right and. I you know we, we. If, we measure these things and they these, are let's. Say the DNA. From a tumor that you can measure, quickly. After the start of treatment for a patient with chemotherapy within, a few days of getting chemotherapy these, levels, change so dramatically, because, the half-life. Or the lifespan of these DNA, molecules is so short. That, you can see dramatic. Predictive. Power in and of themselves and, of course those of us and many other groups have shown that those. Measurements. Are are, great. At predicting, the future but, it's, the. Ability to to. Use. That information, and what. Was there before and also, the additional information in. The. Course of disease radiographic. Data we're not gonna get rid of radiology. Anytime, soon, and, it does provide information. Let's. Say a procedure. Has a pathologist. Evaluate. As the. Result of new adjuvant, chemotherapy, as. Before, the surgeon, does the definitive job, of cutting out a tumor, we're. Not gonna throw that information, out it has information, in it I think, the thing I was surprised by was, the complementarity. More so than any one piece being. The, most implement, thats actually good to hear that the the, medical, the oncology, profession, has chosen its tools relatively. Wisely, maybe not even realizing, how wise it. Was so, I'm, struck by this and in thinking about it because a lot of it is predicting, predicting. Forecasting. The future that what the patient state is going to be um. How. Does it affect management so maybe. Since we're not many of us are not oncologists. How, does knowing whether a patient has a relatively. Good prognosis, or a relatively, bad prognosis how does that affect the way you treat, them right do you give up sooner, or do you get more aggressive all, right take us through how this situation changes. Care sure so, let's. Say we're, talking about an aggressive, lymphomas so we're talking about just using. Unlike. Let's say breast cancer or lung cancer, it's not a disease that we have the surgeons help us with cut, out as a way to cure the disease we, need to use drugs in combination when, a patient comes to see me let's say like yesterday in my clinic with. A new diagnosis, we get a, picture. Of, where. This disease, is what's, the stage what's the risk, etc you have a conversation with a patient in general, you say yep what we think we have a 60% chance of curing you with. This regimen, and that's. Good and for Meishan but it's not a whole, lot better than a coin flip right yes I, would. Go home nervous, right you would go home nervous and your oncologist is nervous right the whole team is nervous you're fighting a battle together to, save, a life and, the. Question is the. Things you're doing are. Toxic. They're, expensive and, a. Human beings life is, not. A trivial thing to be playing a, coin, flip weightless so.
Can. You through the course of this treatment help. Even. If it's not for changing treatment help set priorities, right so do. I, prepare. For my grandkids. Wedding. In couple years or, do, i, prioritize. Writing, my will, write, harsh but are you a real, situation these are conversations, I have regularly, with patients, on, the, flip side. Well. If this treatment is unlikely, to work could. We imagine this strategy as a quick, change. Of treatment, that's the experiment, we need to do. But. Yep. This is chemotherapy. It works for 60% of patients to cure them you're not one of those 60%. We, should be putting you on a clinical study of a new drug let's, say these. Engineered. Immune cells chimeric. Antigen receptor. T-cells, expensive. But profoundly. Effective, with a single, dose curing, a large fraction, of patients at home the, disease could we imagine doing such a thing and we've been talking with a lot of folks about that kind of strategy this is the future of everything I'm Russ Altman I'm speaking with dr. Ashe ELISA, about. Chemotherapy. And the value. Of having, better, predictive. Information about, what the future of a cancer looks like so, it sounds from your from, your last answer that, a lot, of this is risk management and, knowing. That it's an aggressive cancer, might, make you more willing. To subject, the patient to very harsh, or even. Investigational. Therapies. But, if the patient looks like they're going to likely respond, well to the standard, treatments, for that cancer then, your, level of risk. Taking. Might go down because your be confident, that the existing. Methods will be is. That a fair summary of I think so I think you. Know in part we this disease is a poster child for oncologist, because the, lymphoma, one but the other ones are, also. Relevant. I don't, think it's about intensity. As much as it about honing. The strategy, based on the information I could imagine for a significant, fraction of patients, we. Give everybody six treatment cycles with the chemotherapy recipe. That that's the recipe for the average patient but not for the individual patient maybe you could get one.
Treatment Or two treatments, and be done so, you could imagine this as down. D. Lowering. Or de-escalating. Or then on. The flip side it. Could help us pick drugs that are more effective, than. Chemotherapy but, we can't ignore, the history of 50 years of research to show that these. Recipes, cure, such such a large fraction of patients so, so, this is very exciting obviously and for the three diseases you mentioned which presumably were in your first theoretical called. It the theoretical, paper. It. Sounds to me like it would have general applicability and I think you even made a reference to that the community, is excited about this and it is now kind of part of the research agenda to see if this can work and be applied to numerous, other cancers, prostate you didn't mention brain, yes etc, yeah actually it's funny you mentioned that prostates the next one on the radar we've been working on. Brain, tumors we are also working on. The. The. The need for these things as data so what can we the theoretical. Framework needs data, but. So. Applying, it to other tumor types and then doing the clinical studies, to say alright you you know risk management, but a therapeutic, risk management, what's what's next, for these folks this, is the future of everything I'm Russ Altman more, with dr. ash ELISA de about oncology, the. Future of cancer diagnosis, and treatment, next, on SiriusXM. Insight, 121. Welcome. Back to the future of everything I'm Russ Altman I'm speaking with dr. ash ELISA, de about, cancer, and current. Trends in cancer, diagnosis. And treatment, so, two things, and we made brief. Of this in the last segment is this idea of a liquid biopsy, biopsies. Are usually scary because it usually means a surgery, and. Liquid is just confusing. So could you take us a little bit more deliberately. Through, this, relatively, new technology that we're hearing a lot about even in the popular, press sure, so. You're. Right and that liquid. Refers, to a liquid. That we're trying to sample whether it's blood. Whether it's urine, whether. It's cerebrospinal. Fluid, etc. But by and large most people have talked about blood and in.
The Blood there are a variety of, types of molecules. Or, analytes. That can, give us some window, into. What the primary tumor looks like. The. These. Include, maybe. Whole cells in intact form you know circulating, tumor cells so, the cells that have broken off or Oken I've just, sitting there in the blood that's right so for blood cancers that's not not so unusual because they tend to circulate, but for solid, tumors we've. Known for some time that even. In early-stage tumors. Some, fraction, of the cells get. Loose and circulate, and that's. Those are called circulating, so that's remarkable, just a just to punctuate, that that means there might be some of my breast cancer cells, if I had breast cancer in my circulating. Blood that's right take it from my arm that's right. Then. The. That's, one class the other class is. Forget. The cellular portion of blood let's, look in the juice that, floats on top of the blood cells when you spin the blood and. That. Plasma. Or serum, in. Large part folks have focused on plasma. As molecules. In it that don't necessarily, need. To be an intact cells they could have broken off and one, class of molecules that people have spent a lot of time on are called, cell free DNA molecules. It's fascinating, because these, molecules were recognized, by a couple of French scientists, in the 1940s. Before the Nobel Prize before. The structure of DNA was even solved, and. That they, they recognized, that these molecules were free and abundant in cell free DNA but. Not that abundant, it's still. It's. Still a, needle, in a haystack problem so. If one word take that DNA and look, for things that tell you something special. About some part of the body you, can find. And. Detect, and infer go a biopsy so at. Stanford, the work of Steve quake and others has been transformative. For medicine. Are. We thinking about using this to, detect the cancer in the first place or to follow its progress as, you treat or whether both, of those are areas of active, active, research so. The. Analogy, I was mentioning to, what, Steve, quake has worked on is for. Figuring. Out whether, pregnancy. Is. Associated. With Down syndrome and. In. The past we used to use biochemical. Markers, and ultrasound, and so on and, being. Able to look for that's caused by an extra copy of a single chromosome, chromosome 21, but, if you look for that in the blood of the mom because, by a few weeks of pregnancy a few percent, of the DNA is coming from the fetus even though a few percent of the cells don't circulate this. Makes it very easy to. Non-invasively. Without, putting a needle through. The uterine. Wall you, know, synthesis, I. Get. A look into this environment. Non-invasively. So. That's, but that that's a disease or, a condition I should say where.
You, Have a whole chromosome, and, that. That you know what you're looking for cancer, is much more heterogeneous. And. The. The. Mutations. Happen all over all, the, chromosomes and you can't take a single mutation and detect it so that the liquid biopsy ideas are to look for mutations in DNA and, help. It inform you about early diagnosis. But, also what. Mutations. Might be there that, could, help you inform a therapy, and then also monitor. A response, is their disease remaining, or not, or is there things evolving, this, is the future of everything I'm Russ Altman and we're speaking about liquid. Biopsy, and cancer, diagnosis. So let me ask one I know as. You know I'm also a physician one, of the things that that happens, when we have these new capabilities is, they, allow us to look at. Diseases. In this case much earlier than we might normally, see the disease and that means we often don't know what to do with the information right, so now, that I can detect the cancer that's in the blood perhaps, before it has any clinical, symptoms and before the, normal, way I'm, using scare quotes the normal way to diagnosis, which is because of the onset of clinical symptoms or something, it becomes, a little bit challenging to know what to do with this information which. Actually leads me to the to the topic which is that there's, this immune system, that there there's I know there are theories, that the immune system is actually doing some kind of surveillance, and maybe helping, us with very early cancers. In. Terms of recognizing, getting rid of them before we ever have problems so pulling. Back a little bit can you tell me a little bit because, I also know this is another very hot area about. How our understanding of the immune system relates. To cancer and new treatments, for cancer, oh sure. So. The, last decade, has been a remarkable. Time. For. Studying, the immune system, and its relationship to. Cancer. In, fact the, most exciting, drugs of the last decade, have involved. The immune system so instead of directly attacking the tumor cells with drugs that kill, the cancer cells you. Now have. Drugs that engage. The. Immune system to say hey wake up and then the. Same drug working, for many cancers, has. An effect and curing. A substantial, minority of, patients with who'd otherwise, be. Deceased of their and obviously the immune system needs a little help right because it's not doing it on its own that's right and this, imbalance that. Happens, we're still trying to understand, all the. Rules. Of the system what are the nuts, and bolts that. Keep. This, system from, doing, its job the way that it was designed. To. But. We figured out a few of those and to basically. Take. The breaks. That are put on the immune system by cancer, cells and say hey this isn't right we can we can get in the middle of this with an antibody, so they're diabolical, I want to highlight what you just the cancer, has figured out ways to get the immune system to calm down, right arguably, inappropriately. Right because. It there's, been pressure on the cancer to do that so that it can grow and they survive so we need to stop and you call them breaks which is a great I love that analogy so we have to figure out how to get the foot off the brake with an iron system, exactly, now, how I think, once the kwid biopsies, become, good enough, to. Detect. Cancers, at an early time that. Might afford us opportunities, to leverage immunity, I don't think we are, near. That time in the next year or two I think it's an emerging, area there are lots of folks that have been working on this problem to build tools that are sharp enough that you, a. Significant. Fraction of early-stage, cancers. But. There are versions of of these things that, that. I think could work towards it for example I don't know if you've heard of a test called Kola guard this. Is a, you. Poop in the proverbial box, instead, of having a colonoscopy. And. It finds a significant, fraction of colon, cancers, that, would otherwise, have been missed because a large fraction, of healthy. Adults who are eligible for colonoscopies. Aren't, willing to have this perhaps.
Not A liquid, biopsy, but another kind yes I guess it depends on what what state your bowels are in but. Yes. So. This. Is exciting what are the diseases that are looking, like, the. Most promising, for these immune, therapies I'm sure there are people listening who, themselves or their loved ones are struggling with cancer which, of the cancers where these immune, based therapies, are starting, to appear and what's on the horizon sure, the, earliest, was, a disease called melanoma, where chemotherapy. And many other approaches. Had not been all that effective and melanoma. Is the poster child for these kinds of of therapies. Lung cancer has been. The. Second so you're picking pretty bad cancers, they can be pretty bad cancers, and seeing this result but a range of other cancer, types now in fact these drugs are approved for, half a dozen cancers, broadly. At. Various stages of the disease but. Also in, any, cancer, if the has certain molecular features, if the mutations, look a certain way so, this is happening now and, physicians. And in the community, are aware of these drugs and if if you're lucky enough to have a cancer. That's Lutton well that's a terrible thing to say but if your cancer does happen, to be and look, susceptible, to these drugs it's out there now absolutely, very, soon thank. You for listening to the future of everything I'm Russ Altman if you missed any of this episode, listen, anytime on, demand, with the Sirius XM, app.