 Can you hear me okay? I want to thank the organizers for inviting me to speak today and Dr. Swain for sharing the podium. So a lot of discussion today about point of decision, a point of care decision support. So I'm just going to give you an example of what we've done at Vanderbilt just as a representative example of what can be done. So many of you may know that cancer has been for more than 100 years really described from where it came from on the body as well as what it looks like under the microscope. But we know really that at the genetic level many cancers can differ especially in terms of what is so-called the driver mutation, i.e. the mutation that not only induces tumor genesis but then is required for that tumor cell to survive. And so classically melanoma for example has been described where it comes from on the skin but now we know from tumor profiling at Vanderbilt for example and elsewhere that there's really multiple subsets that are clinically relevant. At Vanderbilt we've initiated routine tumor testing, we've tested over 2,100 specimens and again a large fraction of these patients, tumors will have specific driver mutations that are potentially actionable with targeted therapies today. And as a result of the genotyping 61% of those patients have gone on to a clinical trial specifically in melanoma, a big comparison to the 3% nationally that go on. So the reason I think I'm talking to you today is because there's a huge knowledge gap even in the oncology world as to what to do with all these mutations. We built gene panels that only were testing for about 40 to 60 mutations and even then some fellows and staff at our Vanderbilt were having difficulty deciding what to do with those specific mutations. A lot of people have talked about this but essentially there's surveys that reveal disconnect in the understanding of and communication about genetic mutation testing among healthcare professionals and cancer patients. And so one of the things we did was first to get rid of the old electronic medical record for reporting gene mutation testing. As many of you may know at many hospitals there's a scan PDF from the molecular pathology lab that goes into the chart. It's very hard to find that report. It's also hard to see where the result is. And the challenge for us was really how do you start to report multiple mutations in multiple genes at the same time and whose role is to curate all that knowledge. And there's no clinical trial information or therapeutic implications for the results. And so at Vanderbilt we actually control our own medical record. It's called star panel so we can adapt it. And in conjunction with Mia Levy, a very talented biomedical informaticist, we've essentially put into the chart the results of genetic testing of our patients. Here in particular is what we call a dashboard or a white board where we can see by patient the exact mutations that we're tested for in the specific melanoma panel. And then we put a lot thought into saying what does a clinician really want to know, they just want to know positive or negative. So you can see if a yellow result is positive and a gray result is negative. If you really want to know the exact mutation, you hover over the yellow and it gives you specifically all the different kinds of mutations that you looked for. And you can see that a clinician at the point of care with five minutes to see his or her patient could get very confused, especially at the genomic level of the significance of all these mutations. Now, again, I'm also a practicing oncologist. I know that you have five minutes sometimes to go see your patient. You want to just look it up and be able to discuss in an intelligent manner. So within the chart, if you forgot what B600E is, you can just click on that. And it takes you to MyCancerGeno, which is a freely available website designed to enable a genetically informed approach to cancer medicine. Now, at this particular website, you can see in very brief detail, we wrote it, or the mantra is that a clinician should be able to catch up on all the information within five minutes. It will tell you, for example, the location of the mutation, the frequency of that mutation in melanoma, the frequency of the specific B600E mutation among BRAF mutant melanomas, and then the implications for targeted therapy. In addition, what we're most excited about is it can help you find clinical trials. And so if you click on the clinical trials tab, it will take you to BRAF mutation directed melanoma clinical trials, not only at Vanderbilt within our own system, but also in Tennessee, in the United States, and internationally. What Dr. Levy did was to download all of clinicaltrials.gov and then using natural language processing and machine learning. You'll use gene names to search that and annotate it so that you can search the trials by gene status. And then if you click on specifically, for example, that number, it will take you to the clinical trial that's being done at Vanderbilt, and you can check eligibility. You can click on the United States and it will tell you which sites around the world, in the United States, particularly have trials directed towards BRAF mutant melanoma, and then you'll click on the specific site and it will take you to nciclinicaltrials.gov. Again, this is a website that's designed to enable a genetically informed approach to cancer medicine called Mycancer Genome. We currently cover 17 cancers, 25 genes, and 289 disease gene variant relationships. We also have clinical trial search where you can search 36,000 cancer trials, 135 cancer diagnoses, and 437 cancer genes as defined by cosmic, which is the catalog of somatic mutations in cancer run by the Sanger. We want to be the cosmic for clinicians, which is essentially not available except through this website currently in the world. We also built something called Direct, which is the DNA mutation inventory to refine and enhance cancer treatment. We started with EGF receptor mutations in lung cancer and basically looked at all papers since 2005 and have more than 1,000 patients in the database with 188 different kinds of EGF receptor mutations. Again, as a person who was involved in the discovery of EGF mutations, I used to get emails all over every week from people. I had my patient's tumor genotype that has this mutation. What am I supposed to do? Well, now they can just go to Direct and then they can find out the significance of that particular mutation in EGF receptor. And we hope to expand that out. And actually, we think there should be a national or international effort with this kind of database so that we can actually keep track of all these rare mutations. We also built the interest-only complete list of targeted therapeutics, which you can easily access on the website. And there are other educational things on the website as well. Right now, this is a worldwide collaboration. It's basically based on philanthropy and grants. We have 49 contributors from 18 institutions in eight countries. And we now are starting about in, we started in January of 2011. And we now have more than 2,000 site users per week, according to Google Analytics, from 134 countries around the world in all 52 U.S. territories. And then this slide is just to show you that it's a huge collaborative effort. We do have a lot of people at Vanderbilt, but our contributors are from all over the world, and we ask experts throughout the world to help contribute on their specific disease and gene variants and mutations. Thanks. Great. All right. Thank you very much. So we have questions for our oncology colleagues. I think Mark is going to start off. Thank you. One comment related to the aggregation of data, again, and we've got a great example on oncology of how this can work. And that's the children's oncology group that, for a variety of reasons, were faced with the challenges of rare tumors and made the decision from the get-go to aggregate data. And the number of children that are on trials approaches 100%. And so in some ways, I don't think we'll be able to scroll back and begin something like that, but it's certainly a worthy goal. The question I have for you, Bill, is tell me a little bit more about the outcome measures that you're using to determine the impact and effectiveness of the MCG program. Yeah, that's a great question. Right now, all we have is a user survey that people can ask us questions or give recommendations, et cetera. We had multiple survey requests. Right now, the content is written for physicians, biophysicians, and physician scientists. But we've had a lot of requests to translate it into patient-centric information. And I'll get to your detailed question, but we've also had requests to translate it into French, German, and then other medical institutes wanting to link to us and or suck in the content so that they can report their outcomes. In terms of actually whether it's influencing patient care, we have not measured that specifically. Right now, we're trying to help clinicians and oncologists really use the genetic information. We know patients are getting their tumors tested. The bulk of mutations that are tested for include, like, V600E or actionable ones, like an EGF receptor, where people do know what to do. But there are some rare ones where we don't have. There's no evidence, as we've been discussing in terms of the guidelines. And I think the reason I wanted him to present it to is because we would like in ASCO to include these kind of things, because our cancer link, one of the main goals is looking at outcomes for all these patients who are treated, not just with genomic information, but information in general. Yeah, and one specific question or point. You mentioned that 65% of your Vanderbilt patients are on trial. How much of that is attributable to this, or was that just a cultural thing that predated this? Yeah, so some of that involves the fact that, for example, melanoma, we have lots of trials that are genome directed. And so I think there's a huge referral bias for patients to come and get specific care for their specific mutation. We have trials for all the different subsets of melanoma, for example. I'm wondering when you work with these cancer genomes, are you getting more information than the candidate genes? Or are you really just focusing on the driver mutations in cancer? Yeah, so right now, at least in Vanderbilt, we're just focusing on the driver mutations, but we know there's, as other people have talked about, there's gonna be large groups of people who are doing exomes or genomes, et cetera. Right now, the website is only designed to help you with a single mutation and a single gene and a single gene disease variant. So I think the next frontier will be, how do you deal with multiple mutations? However, there are companies that many of you may know, for example, like Foundation Medicine, which profiles more than 200 cancer genes, full exomes, including multiple fusions, et cetera, and they give much more extensive reports, some of which are clinicians still have trouble interpreting if they're not necessarily pathway-oriented in terms of cancer biology. One thing that you'll probably be struggling with as well as everyone is how do you deal with the mutations that you find that are not related to oncology? So you're dealing with cancer, but then there are all those other findings. And so have you run across any of those yet? Or are you making plans to deal with other subspecialties? You wanna describe it? Sure, well, in cancer, right, at Vanderbilt, we're only testing for known variants, but obviously everyone's moving towards full exome or finding variants of unknown significance. Right now, as Dr. Swain alluded to, at least in cancer, you can say there's a mutation for which there's an FDA-approved drug and there's an indication in that specific disease. Then you may get a mutation like V600E in a colon cancer for which there's no FDA approval, but both there's FDA approval and a different cancer. And then, and you can move on down the chain. You know, that's a mutation of clinical significance but not necessarily in that disease. Then you move on to variants of unknown significance, et cetera. I think a lot of us are wrestling with that. In fact, I was just reading the science paper coming over about how you can also re-identify patients by all of that data. And I think we all have to grapple with that as we move towards these large databases. Great, Gene? For Dr. Swain, it seems to me, relatively the other subspecialties of medicine, you really have a challenging task because you're having to put this all together as tons of data rolls in. Are there lessons learned about how you've done that that could inform what other people are gonna try to do to get ready for it before it hits? Well, I think that CancerLink is the lessons learned. And we're just still, we're continuing to learn lessons and the prototype is just being rolled out. So we definitely will and we plan to publish a paper on it on the issues. It's not been easy, as you can imagine, using all different electronic medical records, trying to get it all together, getting from my institution, for example, which is MedStar, the lawyers are not excited, would be an understatement, about giving information to a company to anonymize. That's a huge problem right there, the HIPAA issues. So there are a lot of things that we will have to look at and we've worked with. But the plus is that at least 130,000 patients' data is there, so the precedent will have been shown and hopefully in seeing that and seeing that we can show outcomes and that we can show benefit, quality, looking at value and things like that, others will see that and actually agree. Yeah, so I think that that's a really important point and something that I think we should highlight as we think about how to address some of these issues. And this has come up at other meetings as the concept of the trusted broker or the safe harbor and what role could perhaps the policy shop of genome develop relating to defining those types of safe harbors where we could do this very important job of aggregating data. I think that would be terrific, really important. Can I comment? Yeah. Quick comment on that, in terms of our direct database, the DNA mutation inventory to refine and enhance cancer treatment, you would be surprised about how many barriers there are in terms of getting the mutation status for example, trials from cooperative group trials, et cetera. Originally we wanted to make that database easily searchable by anyone, but then because groups would give us data that had already been published but had not necessarily been published with the fine mutation data in detail, they didn't want that shareable. So we had to basically make it that you ask us a question, what is your specific mutation of interest and then we would give the result back. And for example, companies are also very reluctant to share that information, et cetera. It would be good to have an honest broker in the middle that could get all that information. I think the other thing that's really interesting if you actually talk to patients, they're very much for this. So they're the least of the obstacle in getting this done. And I think it's important in this kind of setting too, as we go forward in talking about guidelines that patient advocates really be involved because they are our advocates. They want this done. They want quicker therapies and all of that. Great idea. Jonas, please. I was going to ask you exactly that. Are initiatives like patients like me somehow pushing for this to happen? Patients pushing for what we're doing specifically? Yeah. So initiatives like patients like me, for instance. Some patients. I don't know that specifically, but I know the patients really, in looking at different surveys and all have been very willing to do this. And they're not pushing us specifically, but I think that they will definitely be great advocates for it because it helps them in the long run. You have metastatic cancer. You're not cured in most situations. So they all know that and are very happy to contribute. And I think we just need to educate people, patients, even more about it and make sure that the data is not used inappropriately. Great. Other comments? Super. Well, this has been wonderful. Thank you so much. Our next topic is Mark. We should thank our speakers. Thank you, Mark. Mark reminds me that my manners aren't glued too closely to me. So he sits next to me instead. So in terms of lunch, we had asked them to provide it a little bit early in case we ended early. I don't think they're quite ready yet, but it should be out there momentarily. It will be just to the side here. We are having a working lunch, so really we need you to get your lunch and bring it back in. And with the size of this group, it's going to take the full amount of time to get it back in. So we will reconvene here at 110, hearing from the Heart Association. Thank you.