Discussing Signatura

In this episode, Terry Lynn Arnold, sits down with both Dr. Wendy Woodworth and Dr. Azadeh Nasrazadani.

Transcript

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Terry Arnold: Hi, I'm Terry Lynn Arnold, and you're with Talk IBC, and I'm so honored to have Dr. Wendy Woodward with us today, who's the Executive Director of the Morgan Welch Clinic, and also Dr. Razidani. I didn't do it right. It's four syllables. Say it again?

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Azadeh Nasrazadani: Nas Razidani.

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Terry Arnold: Razidani. Okay, I've been practicing, but I still knew it. There's a reason we call you Dr. Ozzy, and Dr. Ozzy is one of the breast oncology specialists for inflammatory breast cancer at MD Anderson Board of Watch Clinic 2, and I asked him to be with us today, and just to give you a timestamp, it's late March of 2025, 26,

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Terry Arnold: March 26th.

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Terry Arnold: been a long year, and the reason we're having this conversation today is to talk about the blood biopsy test signatory. There are so many questions, so we're going to go from super low end of what is it, how does it work.

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Terry Arnold: all the way deep in the weeds for all those deep, deep questions that people want to know. So who wants to start, ladies?

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Wendy Woodward: Dr. Ozzy, go for it. Tell them about, those assays.

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Azadeh Nasrazadani: Great, so essentially this signatera assay, what it's aiming to do, it's a blood test, just as you would have any kind of a blood draw, and what it's looking at is for evidence of ctDNA, or essentially material that's DNA that is presumably from the V tumor that was identified in your body.

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Azadeh Nasrazadani: And the idea being that

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Azadeh Nasrazadani: trying to figure out how can we interpret the quantity and the presence or absence of these results, and whether that correlates with, whether there'll be recurrence, how the state of the disease is going, whether we're responding to therapy, all kinds of questions. So, that is the overarching goal of what it is, and kind of what it really is.

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Wendy Woodward: And I'll just give a little background broadly on these types of tests, which are all looking for MRD minimal residual disease.

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Wendy Woodward: Because Signatera, in some ways, is the first to market, so we're seeing a lot of it, because it can be ordered, and it can be paid for by insurance.

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Wendy Woodward: But it's by no means the only one. And so these come in two flavors. There's a type of minimal residual disease test that's not based on your personal tumor, it's just looking for suspicious DNA in your blood that's probably tumor DNA. And then there's a test like the Signatera test, where we actually send your tumor out so that they can look at yours specifically and design your Signatera test

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Wendy Woodward: Based on that, that's a bespoke assay.

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Wendy Woodward: So those are two, and then the next piece that's coming is, how sensitive is it? And so, if we might imagine that Signatera could pick up one piece of tumor DNA in a thousand, the newer ones are going to pick up one piece in a million. And so they become much more sensitive, and then you have to ask the question, what does positive mean? Is there… where's the right barrier? Where above this, the fact that we found this molecule means

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Wendy Woodward: something, and below this, it's just noise.

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Wendy Woodward: And those are all pieces that are still under investigation.

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Terry Arnold: It's interesting you said that about, you know, like, what is the level, because that's one of the things I'm hearing is, like, when you know… when you do the standard CTC test, there's levels that you know that this means this. But with this test, I've been told they're not really sure what that threshold is. Is that a fair thing to say?

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Terry Arnold: Like, the number of starts freaking you out. It's kind of like what we want to know as patients, right?

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Wendy Woodward: Yeah, I think we all just… if we were just to step back from our medical scientific approach, we'd all love it to be zero, right? We want to say, oh, zero is the only thing that matters.

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Wendy Woodward: But if you start to pick up tiny, tiny, tiny amounts, and some of them could be false positives, or some of them could be meaningless, then we have to know where should we really set that? And we're relying on the companies to do that work to give us an answer, but it's still in progress.

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Azadeh Nasrazadani: Towards…

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Terry Arnold: Go ahead, Dr. Ozzie, I'm sorry.

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Azadeh Nasrazadani: Oh, sorry, just to say, to add to what Dr. Woodward is saying, it goes back to the sensitivity also, right? Because, yes, the things that we know so far, we know that negative is better than positive, but it all goes back to that sensitivity. We have some patients who will continue to get this testing, and it's, you know, very, very borderline positive, negative, and it kind of fluctuates, it goes back and forth.

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Azadeh Nasrazadani: And, you know, to Wendy's point, we really don't know quite yet what to make of that, how concerning that is, how to really interpret that. So I always tell patients this is just information.

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Azadeh Nasrazadani: We do not necessarily make big, decisions, clinical decisions, based on this alone.

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Azadeh Nasrazadani: And it all goes back to sensitivity, and not really knowing for each different kind of breast cancer if the number matters differently, right? So, perhaps having a number 3 or 300 means very different things for someone who has, like, inflammatory breast cancer, or someone who has

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Azadeh Nasrazadani: Hormone receptor positive breast cancer versus triple negative. So, a lot of these things we really don't know, and it's very hard to counsel based on that data void to date.

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Terry Arnold: to say this, because I'm talking to a lot of patients who are finding this very distressing.

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Terry Arnold: And I keep telling them there's a reason it's not prime time yet, and you have to talk to your doctor and get it really individualized, and a lot of us are very… a little crazy, because we've been misdiagnosed or given the wrong information, so we're always a little suspicious, shall I say.

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Terry Arnold: And, but I tell them to talk to your doctor about the individuality, like you just said, triple negative. If you're triple positive, all that matters in this test, does it not?

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Terry Arnold: Or does it not?

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Azadeh Nasrazadani: Probably. The short answer is we don't know yet, but I think based on anecdotally, or based on how we know the clinical, the, you know, the natural history of each kind of breast cancer evolves and acts, we anticipated to, but we just don't have that information, to speak more to that.

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Wendy Woodward: And I can say, speaking to the stress, Dr. Nasras Adani and I, had got an email once from a patient you know well, who was just highlighting this, this juxtaposition where we'd love to say, we don't know the answer to that, so let's just not do it, or use it, or share it with people until we figure it out. That feels very comfortable scientifically.

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Wendy Woodward: And she very eloquently said, you know, I deal with the reality that I have metastatic breast cancer, I can handle the stress, and I want the data. And that was totally reasonable, right? We understand that, and so that's part of why it's moved forward before the data is really clear, because it is available, to patients, and patients, by and large, have articulated to us that they would rather have the data

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Wendy Woodward: than not.

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Terry Arnold: I'm hearing, too.

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Azadeh Nasrazadani: that exact person, I was thinking of her and how well she mentioned that, and she's right, she said.

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Azadeh Nasrazadani: I have a right to decide if I want to be anxious about it, and I thought that was very deep, and it's true, but I think that that kind of puts it on us to really be able to be as transparent as possible and say, okay, here's what that means, here are the caveats of this. I will share your information, but let us kind of be honest about, or transparent about what this does and does not mean, and how we can look at the data together.

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Azadeh Nasrazadani: Are the results.

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Terry Arnold: One of the things I'm hearing from patients, they say, you know, I'm at a medical facility, and one doctor in one room will order the test for their patient, but another doctor in the other room, the same facility, won't. There seems to be some different,

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Terry Arnold: feelings about that, on the doctor's side, probably because what they… what they're seeing. But also, too, I've seen people get a hot read in the blood test the same day their PET scans were negative, and vice versa. Is the test more appropriate, say, for blood…

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Terry Arnold: Bone versus lung, liver… do we know any of that?

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Wendy Woodward: I don't think we know. I think it's going to be individual biology. Some people have… we know, even not thinking about Signatera, that some people have much more pet-avid disease than others.

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Wendy Woodward: And so there are going to be some patients who don't have particularly pet-avid disease at that moment in time, where maybe the test can pick something up, and we'll have other people where maybe they have pet-avid disease, but it's not shedding into the blood.

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Wendy Woodward: Right? The way that I think about how radiation helps to cure people is that there may be deposits of disease that are in the areas that the breast cancer started, the breast or the lymph nodes, and radiation's going to get rid of those.

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Wendy Woodward: So if they're not shedding into the blood, or if systemic therapy has done a good job of eliminating whatever was being shed into the blood, then you could have a pet that demonstrates you have these issues, and not have a positive blood test, because it's here but not there, and radiation hopefully will get rid of that. We also have seen examples in the literature where if you have a known lesion, and you use radiation or a therapy to really eliminate

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Wendy Woodward: it can shed into the blood, right? Because you're picking up a fragment. You don't know if it's a whole tumor cell that's capable of growing and spreading, or is it something that's being destroyed and there's a lot of

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Wendy Woodward: That's going into the blood. And so that's part of the, again, unknown of the timing of when to get it, to try to avoid some of those caveats.

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Terry Arnold: One of the reasons I wanted both of you in the conversation, because obviously, Dr. Woodward, you're the Executive Director of the program, so you're looking at everything, and I think all of you look at all very trimodally, but you, as a radiation specialist, might have a different thought

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Terry Arnold: on this versus Dr. Ozzie, who's at the other end giving that… that chemotherapy. So.

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Terry Arnold: Does that bring a different conversation to the table for a patient to think about on who they talk to? Like, am I talking to the one who's giving me the chemo? Am I talking to the surgeon? Am I talking to the radiologist? Am I talking to my long-term wellness follow-up? How can we, as patients.

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Terry Arnold: get what we need, ask the right questions. Do you have some feedback on that?

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Azadeh Nasrazadani: Oh, absolutely. I think it makes a very big difference, and I think Dr. Woodward illuminated well how we think about it in different ways. You know, certainly, I…

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Azadeh Nasrazadani: when I see in clinical practice, and to go back to your initial question, the differences in who will get it and who won't get it, ultimately, you know, we are all trained to follow, kind of, data-driven guidelines.

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Azadeh Nasrazadani: And so while these testing modalities, Signatera, for example, it is FDA approved, there are actually no standardized guidelines on how to use this information. So, like, an NCCN or the things that the governing bodies that tell us what to do with this. So a lot of it is, truthfully, I hate to say this, but

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Azadeh Nasrazadani: and not… maybe not quite cowboy medicine, but we're all trying to do our best to interpret it to the best of our abilities and use it in a responsible way. And it goes back to our clinical judgment, ethically, how we think we should be using it. In many cases, we'll always say, hey.

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Azadeh Nasrazadani: we will get this test if it will change our practice. And so, if some clinicians feel, I do not put enough stock in this to be able to, you know, do right by you and make the right decision based on this information, I shouldn't get it.

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Azadeh Nasrazadani: And so I know that there's a big active debate in our department, and our consensus, our, you know, kind of our overall consensus is we very much steer away from it for now, unless it's part of a clinical study where we know that we are getting

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Azadeh Nasrazadani: information that will, in a very structured way, tell us how to then use it. But, you know, as I see a lot of second opinions, a lot of people from different facilities that come, and it's very interesting to me, how creatively, I guess, we're using this information. Again, everyone trying to do their best to

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Azadeh Nasrazadani: determine what does this mean in what context, whether you're using it while you're getting neoadjuvant chemotherapy in a curative intent setting, or you're getting it in the metastatic setting, where you're trying to guide, is this concordant with the imaging, the PET scan? Does this match? Does this not match? If it's a disease that you can't really get a good sense of measurements.

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Azadeh Nasrazadani: should I use this to give me one more bit of information? And so, it's a really interesting, you know, academically, it's incredibly interesting how… what the potential of these kinds of assays are, but to really… I think it's a really important thing to highlight for our listeners that I don't think any of your clinicians are trying to be mean one way or another. They really are trying to just do right by you and figure out

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Azadeh Nasrazadani: can I use this? Can I harness this information to make sure I'm making better decisions for you? And it's based on the level of comfort, and not even talking about the anxiety of it, but can I use this to make a better clinical decision? And I think that's where that comes into play.

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Wendy Woodward: There's a very practical.

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Terry Arnold: We were not able.

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Wendy Woodward: Operational piece to this, which is that… If you order a test.

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Wendy Woodward: you're going to end up spending time talking about it. And the reality is, if you have 30 patients on your template for a day, and these are the, you know, behind-the-scenes, nuts and bolts reality of how it goes.

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Wendy Woodward: You're spending the day really trying to make sure that you put time where people need it the most, in the exact right amount of time to meet everybody's needs.

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Wendy Woodward: And if suddenly there's an hour or two-hour conversation about a test for which we have no answer, you're taking time away from other things, and it's hard to navigate. And some people

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Wendy Woodward: have said, you know, we have to have a whole different workflow for this. In our access center, as we're bringing in these second opinions, where somebody was getting perfectly reasonable standard of care and then got a test they don't know the meaning of.

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Wendy Woodward: and they want to come see MD Anderson for that, we have a whole side, workflow now for that, because it's a long conversation, because there's no answer. It's so much easier when you're like, yes, you should do this, and no, you should do that. And that's not how this is.

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Wendy Woodward: So there's a practicality to it, too. Some people just acknowledge, like, I can't possibly address this in the space that I have right now, and it's not changing anything, so I'd rather not get it. So that can weigh into it also. I would say for the IBC patients, we decided in our multi-team clinic

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Wendy Woodward: as a group, because Dr. Lucci has a minimal residual disease study open.

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Wendy Woodward: And it's standard of care, that we would order it everywhere that we can practically get it.

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Wendy Woodward: And that way, we can collect that data on his study, we can look at it, it's a very unified group, right? So it's not like, oh, this patient got it, she didn't know, so I did it, and this patient got it, but she wasn't. And we can, in a very unified way, do it. And then that may impact whether or not, as things roll forward out of multi-team clinic, it continues to be ordered, and with what frequency it turns all into a gray

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Wendy Woodward: morass there.

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Wendy Woodward: So that's the one place where we have a little bit of consensus

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Wendy Woodward: we know we don't know, we know we'd like to know, let's order it when we can. And so that's a place where sometimes we're getting it, but it could mean that down the hall, somebody who's not involved in that multi-team clinic may be like, I don't order this, what are you talking about? And so that's… some of that's communication on our part, but some of it is physician preference, and

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Wendy Woodward: I'm trying to figure out how to use the time most wisely.

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Azadeh Nasrazadani: That was so much.

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Terry Arnold: Anytime somebody asks me about this, I'm constantly saying, first off, let me say, this is not prime time.

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Terry Arnold: this is not prime time, because I feel like sometimes, you know, the patients feel like they're drowning, and they will just climb on top of anything they can to save themselves, and so there's a lot of hope in this. But, you know, it's not prime time. It doesn't mean it doesn't have value, but I love what you said about, do we do this test when we don't know what it's actually

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Terry Arnold: It's on the spot, ballpark. If this test ends up being magic.

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Terry Arnold: what is kind of, like, a turnaround time? What… when do you think it could be really prime time? I think it's pretty far out, don't you?

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Wendy Woodward: I think the answer is going to be for each specific question. So, from a patient standpoint, you might be getting it longitudinally, and it feels like, oh, I'm just using Signatera. But from a science standpoint, you've got to answer the question at every time point for every group of patients.

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Wendy Woodward: So, there is emerging data. Does it dictate whether or not you would have a pathologic complete response? There's a big study that just came out, and the answer was kind of no. It was 50-50.

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Wendy Woodward: We're still trying to answer that question in IBC, because

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Wendy Woodward: We wonder then, could we act on it? If we could know for sure you had a PATH CR, could you have a smaller axillary dissection? Right? We know that the smaller axillary dissection only works in patients who have a PATH CR, so if it could help us predict those, maybe we could make a change that benefits toxicity or something like that. So we're trying to study that, but we've got to ask at that point in IBC, at that moment.

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Wendy Woodward: Then you could say, what about surveillance? And you have to say, okay, well, what about, like, what if it was positive right after surgery? What if it was positive at 6 months? What if right after surgery you had chemother… you had disease left, and so Dr. Nasra Azadani carefully picked out the very best therapy you should take to make sure we reduce that recurrence.

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Wendy Woodward: And 6 months later, it's lower, but not gone.

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Wendy Woodward: Does that mean your adjuvant therapy is working really well, and you should keep using it until it's gone? Or does it mean it has done all it can do, and it's not going to get rid of the rest of this, and eventually it's going to recur? And should we do something different now, or should we do something different later? Because not everybody does recur. And so, that's the challenge, is that we don't ever want to deprive people of high-quality therapies that have been

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Wendy Woodward: well-tested in thousands of women that we know have benefit. For the grasping at straws, I feel like I'm drowning, let's pick something different.

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Wendy Woodward: And so staying the course is a little bit hard, but that's really where we are. And I do think in the next, certainly, 5 years, but maybe even sooner than that, we're going to see study after study come out with different assays at different time points, and then we're going to have to try and

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Wendy Woodward: take all the pieces. I think one of the… one of the conversations that has been everywhere in the medical field and science since COVID is how did we lose the trust of the general population around recommendations and guidelines and all of these kinds of things? And one of them

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Wendy Woodward: Is that it is… it's never scientific to take one result and say, oh, this is the answer.

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Wendy Woodward: And then you're gonna find a different result, and it's gonna be different. And people will be like, oh, you misled me, you didn't tell me the truth, this was wrong, now I don't believe you. And that happened in COVID because it was happening in real time. There was no information. Then there was one, we all looked at it, and we're like, this is the answer. And the next thing came out, and we were like, oh my god, that's not the answer.

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Wendy Woodward: But that's how science works, right? You get the first study, and what we do, which nobody likes, is, that's the first study, I'm not sure yet, I'm gonna wait for the next study, I want this detail and that detail, and you wait till the whole body of literature comes together, and you put the puzzle pieces together, and you say.

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Wendy Woodward: The gestalt is this, and here's how well it applies to you. Maybe you're really on the fringe here, we don't have a great answer for you.

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Wendy Woodward: So that's the challenge. We're in this same space as we were when people were trying to understand how COVID worked, and we're watching these individual pieces of data come out one at a time, and looking at them, when what we want to do is stand back and say, get a bunch of data together, get all the pieces, and let's see the whole picture, not just a piece.

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Terry Arnold: I love that you said this, because this is the deep weeds I wanted to get into, because there is mistrust right now in the medical community, and there's just a lot of stress generically in life right now, I think. But one thing that's interesting to me is I'm old enough to remember when AIDS hit really hard.

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Terry Arnold: And someone in my family was exposed to AIDS due to a blood transfusion, and I was watching that information come out in real time, and and I kind of feel like I'm seeing a repeat of that. And I guess I start every conversation with the IBC patient I talk to, this test is not real time.

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Terry Arnold: And to not hang your hat on it too hard? Yeah.

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Wendy Woodward: I think that's the right.

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Terry Arnold: Message.

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Wendy Woodward: You know, we… it's nice to see it, we're all learning as we go. We don't know when the tipping point's gonna come, that we're like, okay, wow, that's really the answer for this.

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Wendy Woodward: So it's fine to see it together, but we do kind of want to think about it from that perspective. We're not… it's not the same as a Phase 3 randomized study with 3,000 patients at all.

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Azadeh Nasrazadani: just to add to that, the timing question was really interesting. It really does give another flavor. So, so much of our time is spent just talking about what is it? Should I get it? But when should I get it? Should I get it specifically? And a lot of that, you know, that complicates things, because if someone is getting in the middle of

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Azadeh Nasrazadani: curative intent, aggressive therapy, that we are really doing the things that have proven themselves. You know, having a positive test may not matter, because that's the whole point of it. That's what I try to tell patients that. That's the whole point of your chemotherapy. If there is something there, that is what this is for, because if we could just…

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Azadeh Nasrazadani: have surgery and call it a day, that's exactly what we would do. Or if you're getting in the middle of proven, like, if you're getting abemacyclib or radiation, that is what the point of that is. So it really complicates

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Azadeh Nasrazadani: the interpretation of these things when I will not necessarily… I have no plan to change the therapy, regardless of what that result is. And that's a really hard thing to sometimes convey of, sure, we can get this test.

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Azadeh Nasrazadani: But I want you to know that I am not going to change what we're going to do, no matter what that result is. And it's… it's hard to,

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Azadeh Nasrazadani: Convey that without having some degree of mistrust of why.

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Terry Arnold: I want to say something, because, like.

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Terry Arnold: I've had women call me and say, I had the test.

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Terry Arnold: I had a hot read, and then a week later, I had a hot PET scan.

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Terry Arnold: And I always say to them, but how many times did you have the test before?

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Terry Arnold: That you didn't… Have a hot read.

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Terry Arnold: and you still had a negative, or you… or whatever, I'm trying to say it the other way around. But the thing is, they think, okay, they notice when they had a hot test, and then a hot pet. They don't notice when they had a hot test.

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Terry Arnold: But then their PET scan was clear. Do you see what I'm saying? And I said, it's almost like when you say, oh yeah, my breast is swollen because I was…

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Terry Arnold: You know, I heard it the other day, somebody threw a ball at me, and I got hurt. When you hear that a lot about, you know, inflammatory breast cancer presentation, you kind of notice when the things couple together, and you don't worry about when they don't couple together. So I'm constantly telling women, this is not prime time to talk to your doctor, find out. But how can we, participate in more studies? What can we do to help people participate? Do you feel your enrollment?

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Terry Arnold: His studies is down right now, or is it pretty decent?

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Wendy Woodward: I think it's pretty decent. I think what the pros and cons are the way you get more people on study is to have a simpler, less rigorous study. So you have a registry, right? When we say we're getting Signatera for everybody in the IBC Multi-Team Clinic when we can do it, that's a registry. That's not going to answer

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Wendy Woodward: the high-quality question that you would get if you said, I'm gonna get this test at exactly this time point in patients who are at exactly the same place, who are getting exactly the same therapy.

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Wendy Woodward: Right? But then you would have far fewer patients eligible for that study. So we're enrolling lots of people, and we're getting lots of registry data. People do this other type of research, which is also provocative, but not nearly as high quality, where you say, let's look at all the people who got one.

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Wendy Woodward: Let's pull out all those patients and look at their results. Well, that's a total hodgepodge, right? So, you could end up having a result from somebody who was right after surgery, somebody who was right after they progressed, somebody who was, 2 years out. So you have all these different time points, and by the time you parse them out and say, how many people do we have at this one time point? It's actually really small.

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Wendy Woodward: And they are all getting different therapies. So some of the gestalt data we're seeing is pretty messy. It's provocative, it tells us we need these high-quality studies. Some of those things are going on. They're big national studies, of which we're participating in, that are enrolling patients to, different type of blood assays.

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Wendy Woodward: then there's a lot of competition in that space. It's not Signatera. We're proposing a test at NRG, to look at, should we be ablating

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Wendy Woodward: Metastatic, foci in patients who don't have a lot going on if chemotherapy cleared the blood.

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Wendy Woodward: And we see some evidence from that in a trial that came out. Well, when I say, oh, why don't we do that with Signatera, because everyone can get it, it's standard of care, the answer is that's not very sexy. That's not moving the field forward. That's not the coolest, newest, you know, latest thing.

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Wendy Woodward: So then we need, okay, well, now we need a second assay, and so…

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Wendy Woodward: We're just in a space right now where, yes, we're enrolling people to a lot of trials. The difference in quality of trials is vast. We all want to be collecting whatever data we can, but some of it is just observational. Here's what it kind of looks like, and it's not a… answering a scientific hypothesis, which is.

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Wendy Woodward: I think if this test is positive, you should change therapy. Here, we randomized change therapy, don't change therapy, and the outcome was changing therapy mattered. There was a big study in SWOG years ago.

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Wendy Woodward: about circulating tumor cells in patients with metastatic disease. And you'll remember Massimo Cristofinelli, really opened this up and demonstrated that patients who had 5 CTCs really seemed like their disease was going to progress.

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Wendy Woodward: So the trial was, if you had 5 CTCs, you could continue doing what you were doing, or you could be randomized to whatever your doctor thought would be better. No difference. Absolutely no difference. And that really was like a lead balloon of…

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Wendy Woodward: I don't know what to change here, and so if I'm now just moving off of therapies that seem like…

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Wendy Woodward: They're well-studied to things that we are just guessing at, we're really in a big unknown.

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Terry Arnold: Well, I am watching the clock, because I don't want to cut anybody off. I know Dr. Woodward's got a hard stop here, but one thing that,

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Terry Arnold: I'm hearing is some very good explanation about why it's not prime time, what we're doing, what we're going, why doctors might be offering it based off what action they're going to take. I want people to feel hopeful about their care. I'm about to celebrate. Yesterday was the 18th anniversary of my surgery for my.

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Azadeh Nasrazadani: I will say.

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Terry Arnold: ctomy, which is.

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Wendy Woodward: An exciting thing.

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Terry Arnold: You know, when I was… I know, and…

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Wendy Woodward: That means I met you 18 years ago.

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Azadeh Nasrazadani: Wow.

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Terry Arnold: I want people to have hope and feel good, and see there is chance for curative intent.

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Terry Arnold: even with stage 4, and feel they can live a long and happy life. But I know it's also a very difficult disease, and we need these answers. So I appreciate you taking the time to talk to me, and I hope maybe we can have another conversation when you feel appropriate about, you know, what more do we know, or what can they do, or what other things do they need to know about, so we're not… I keep telling people, don't hang your hat on this 100%.

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Terry Arnold: There's a reason on the runtime. Is that a fair way to wrap this up?

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Wendy Woodward: It is, and I'll say, some of the research that's going on is going on with the saved blood samples that people gave, where we could, one big bang, say, let's look at 100 patients like this, and see what the result is.

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Wendy Woodward: And I think we'll have a lot more of those, cohorts where we're really beginning to see how do we design these prospective trials in a way that's

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Wendy Woodward: Much more likely to be positive and impactful.

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Terry Arnold: Is there anything you want to say before we go?

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Azadeh Nasrazadani: I just want to say that you absolutely… you're right, that we should all be very hopeful. We did not have these tools before, and so we did not have the knowledge that comes with that. Yes, it is a big can of worms, but there's just such enormous potential in all the different ways that… the ways that we can ask the questions have been so interesting to see, and I think it's going to be very powerful in helping us. To your point.

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Azadeh Nasrazadani: Like, our metastatic patients said, maybe they can be cured. These are really provocative and aspirational goals, so I think the next couple years will be just, you know, astounding, and we should,

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Azadeh Nasrazadani: We all eagerly await those results, as we like to say in academic circles, so… So yes, there's lots of room for optimizing.

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Terry Arnold: I appreciate both of you taking the time, because I cannot imagine the heavy load that you carry, just at this simple fact of there's 30 people on your roster every day for appointments, and let alone all the other things that you have to do to be scientists in this difficult field, but I do appreciate it. And if there's ever a chance y'all want to make a quick snapshot of a talk, I'd love to have you back.

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Wendy Woodward: Oh, we always want to do that, and we're so grateful for the fundraising, and especially in times where science is, you know, not everybody's favorite topic, we… we are grateful.

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Terry Arnold: We, we live for it, literally. We live for it, for other people to live for it, so thank you very much, and we'll end it with hope always.

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Wendy Woodward: Awesome. Take care, thank you.

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Azadeh Nasrazadani: Absolutely, congratulations as well.