Thank you everyone. Thank you for the thank you to Ace for inviting me and thank you to all of you for inviting me here to Dubai. A real pleasure to be here. So I was asked if I could give an update on the American Thyroid Association thyroid cancer clinical guidelines. I'm more than happy to dig into this to what we know. These are my disclosures as I begin and and there's pros and cons to clinical guidelines and I'll start by saying I can't give you the answers to what the 2000 upcoming 25 guidelines are going to be because they're not out yet. What is still active is the 2015 guidelines that you see here. Brian Haugen led a team of us through this and there are pros and cons to the concept of expansive clinical guidelines. As you can imagine the benefit here is you get to dig into a wide range of all the available data and try and establish the best clinical recommendations. But the downside of course is exactly this that they take a long time to develop and if you throw a problem in the middle of it like a pandemic they can be a decade or more in in in formulation. But we are on the cusp of the new guidelines that are coming forth and in fact it is worth noting that actually the size of guidelines which previously encompassed both thyroid nodular disease and thyroid cancer they are so big now they will be split into two separate guidelines that you will see coming forth this year. The 2025 thyroid nodule guideline co-authored by Susan Mandel and Lisa Orloff and then what I'll speak on more here is the 2025 thyroid cancer guidelines co-chaired by Matt Ringel and Julianne Sosa. And here's what I hope I can give you a little bit more information on which is insight into these upcoming guidelines as it relates primarily here to thyroid cancer. And what I can also share with you is the themes likely to impact the recommendations and they will include thyroid cancer over diagnosis over treatment and kind of the steps naturally clinically that are following from that. And then separately I'll speak on molecular understanding of disease and as we use that in particular to lead towards better prognostication and individualized therapy. At the end I will share a little bit with you the pro and con again of these large guidelines because many are starting to talk about whether we should keep a living document and it really speaks to how fast the field is moving forward. And I'll share with you some of those upcoming available data as well. So I'm a clinician like almost all of you I believe are clinicians and I love to start the discussion with a typical case. And in fact I'll talk through two cases. But the question here is what would you do in this situation. A 37 year old healthy female who's found to have a 4.5 centimeter papillary thyroid carcinoma. It's a clinical variant. There's nine local lymph nodes positive for disease. The largest is about 2.3 centimeters and there is some microscopic positive margin and also extra nodal extension. She's also the primary caregiver for her three children. She's nervous. She wants everything possible done to treat her cancer. And so how would you do that and what would you do. But I want you to compare that also to this. A 77 year old elderly female who on an FNA was found to have a 2.1 centimeter papillary carcinoma. It's a follicular variant. There were no lymph nodes seen on her ultrasound. She has no next symptoms and she is actively under care for breast cancer. But she's also considered very high risk and operative candidate because of her diabetes her coronary disease and her hypertension. And so how would you treat her. And I think as the guidelines committee has walked into kind of this next iteration that is very much front and center to their deliberations which is should we treat all thyroid cancer the same. And arguably for 50 60 years this is what we have done. It's this standard that you see here. Everyone was receiving a near total thyroidectomy. Everyone was receiving some amount of radioactive iodine ablation and then almost everyone was on some level of TSH suppression long term. But generally we've been doing this and we now realize that there are consequences to this consequences we don't really like. But the reason it's been happening is in general most patients through this regimen have been cured of their disease and it felt then like we should continue doing so. But the pendulum is shifting back arguing that we probably have been over treating and over diagnosing in the last many decades. 2024 and beyond I believe and this will foreshadow these clinical guidelines will almost certainly see a greater and greater focus on personalized and precision medicine. And so let's talk through that a little bit. The leading theme that I believe will be in the 2025 guidelines will really anchor on this. It will anchor on understanding the future and the normal prognosis of well differentiated thyroid carcinoma and in so doing argue that you can deescalate intervention far more than we have in the past and even consider watchful observation in a non operative fashion. And so what are the data that really back this up. Well it's a story to be told a little bit and I'm going to start kind of with a broad epidemiologic picture and we'll start with just kind of the concept of what is the greatest variable that goes into nodule formation and therefore thyroid cancer formation. And certainly no doubt it's simply patient age. This has been well known the older you are the more likely you are to have a nodule and in fact they're exceedingly common once you are over the age of 50. And it was shown here by Ernie Mazzaferri in this meta analysis a good 30 years ago. But beyond just nodule formation what we've also learned is that having more than one nodule is very common and also a function of age. These data by Nora Kwong and our group published in 2015 really just depicted what was the typical presentation in terms of multi nodularity for anyone who came into our clinic. It would be very similar to your clinic. This was a prospective cohort analysis of about 6000 patients 12000 nodules. And what you notice is that by the time patients are in their 50s or beyond almost half of them will present with two or more nodules each over one centimeter in size. So the key is that nodules of course are a function of age whether you have one or you have many. But the other thing to realize from a public health epidemiologic standpoint is simply life expectancy and the changes that we've seen in the last several decades. These are data taken from the United States but would be similar to many other countries. And the point I'm getting at here is life expectancy. If you were born in the mid 1950s in the U.S. your life expectancy was about 68 years of age. If you were born in 1980 it was about 75. If you were born about 10 to 15 years ago it would be about 80. And so there's an importance to this because medical decisions and approaches to care that we all established 20 to 50 years ago were based on different data and different assumptions in terms of the impact of disease on your future. What we also know is that women live about five years longer than on average than do men. These are from the United States but the data are quite similar in most other developed countries. And of course the key to that is women are much more likely about two to four time fold to have an increased risk of most thyroid diseases and that includes thyroid nodule and thyroid cancer. So the world is changing and these are data taken here that you see from the New York Times published last year. It just gives an insight into that. If you look at populations whether they're young, working age or older and the upper left is 1990 and then compare it to current day in the upper right and then kind of look down in the projections that we see in 2050 which is that there's a much more increased population of working age and older individuals in the Middle East, in Europe, in China. It's changing and in fact specific to the Arab countries you will find data that the demographic changes are such that older populations will quadruple by 2050. So what is on the mind of the ATA Guidelines Committee as it relates to thyroid cancer? Well it is kind of this dilemma that starts the process that we have an aging population who no doubt will have increasing comorbidities and in that population there almost certainly will be more testing and more imaging where more thyroid nodules and cancer are detected and it's in a system often where incentives like time or billing or seeing patients in the clinic can align with doing more procedures like biopsies and yet through all of this there really at times can be more harm caused than there is benefit provided. And if we need comparators there are many. You can all probably think back the last few decades as we've dealt with prostate cancer, PSA screening, as we've dealt with coronary disease and an uptick in catheterization that was occurring. These are very similar health care problems and now I think thyroid nodule and thyroid cancer is very much front and center in this regard as well. So I bring all of that up as kind of an epidemiologic overview because it fits with the data here that are worth showing. Over the last two to three decades what the committee has noted and is very aware of is the dramatic increase in thyroid cancer that we've seen. These are data taken from the United States, the Seer Cancer Thyroid Database, which is simply depicting thyroid cancer incidents as a function of the year. And what you can see here is that in the mid-1990s or so there was a clear inflection point. Suddenly there was a rapid uptick in thyroid cancer diagnoses. These data by Louise Davies and Lynn Lim both published in JAMA and what was going on? Well almost certainly it was increasing cross-sectional imaging, CAT scans, ultrasound use, things like that. And the data by Lim show that what was being found to increase this incidence was clearly well differentiated disease that was local, that was regionalized, and that was often very small. And so while we were finding more disease it was all being treated with that old standard of care that I told you. What's most important in all these data is that Louise showed there was simply no change in mortality through the process of that treatment. So this really does suggest the over-treatment, the over-diagnosis is not necessarily doing more good than it is more harm. So that's where the Guidelines Committee is at. And then you hear them preemptively talk about what's likely to come. They're going to stress de-escalation for that reason. They're going to acknowledge over-diagnosis of papillary thyroid carcinoma. And the guidelines will target two areas that allow us to de-escalate intervention for low-risk disease. The first on the bottom left will deal with less and more appropriate use of nodule evaluation, fine needle aspiration. I'll be speaking on that more this afternoon. The second on the bottom right is going to deal with less surgery. We used to have a near-total thyroidectomy for almost every patient. Now significant increases in just a hemithyroidectomy and really a discussion more often than not these days at times of non-operative watchful observation of a known biopsy proven malignancy. So let's go through some of these kind of clinical steps. What's the translation that you can take home to the clinic? How do you de-escalate intervention? And what is likely the guidelines here are going to, what am I going to foreshadow for the guidelines? Well there are many different strategies. I'm not going to say that there are only three, but I want to show you three clear examples that certainly I think have caught all of our attention. So for example for one as we speak of nodules in particular what we know is that ultrasound is a very good tool and for many patients it tells us all we need to know about their overall risk. I'll go through each one of these and for some in particular here I'm going to focus on older individuals. All that matters is defining high-risk disease. And then a third piece to consider as I mentioned was simply a greater use of less surgery whether it be hemothyroidectomy or non-operative surveillance. So let me give you an example of the real data that support each one of these strategies ahead. Take for example the use of ultrasound and these data by Horvath and colleagues. This was a prospective validation of the sonographic staging risk stratification system called TIRADS. 500 consecutive nodules but what was unique is that not only were they assessed with ultrasound but all of these patients then went to surgery so there was final gold standard histopathology. And so when TIRADS was class 2 or class 3 essentially no evidence of malignancy. All of the malignancy in those that were TIRADS class 4 or 5. And the key really here is that that represented about one-third of the entire cohort harboring one low-risk cancer. So the standard here to think about is that if you start to see such low-risk nodules you really don't necessarily need to pursue anything thereafter. You can watchfully observe them. Let's go to the other side of the equation which is perhaps looking only for high-risk disease in certain populations. And I'll give you a study here that we performed at the Brigham now about seven years ago. Zhihong Wang was the first author because we like you had kind of a standard of care of patients coming in. We had kept a consecutive database since the mid 1990s and we started to realize that we had some concerns in particular about those who are a little bit older and what we were doing in terms of benefit to risk. So we define older in this situation by those over the age of 70 years of age. And we simply looked at that consecutive cohort. It was about 1,100 patients 2,500 nodules. Everyone went through the standard of care if you will. What we were looking for is that hard endpoint though of mortality at the end. So what was first eye-opening is that when you see a patient come in who's over the age of 70 for a nodule evaluation they're actually pretty sick. What we found in our cohort is that about 20% one in five had active coronary disease. About one in three had a separate diagnosis of active malignancy. And as we followed that in the electronic medical record these patients forward over five years one of seven of them died of a completely non-thyroidal cause. So then we were asking ourselves well we really wanted to identify those that would benefit therefore even though they had other comorbidities they would benefit from treating their thyroid cancer because it likely posed a more near-term risk than did their other illnesses. So what was that number needed to help it to identify those 17 high-risk thyroid cancers that you see. It was one in 66 patients. All of them were easily identified at the time of ultrasound because you could see the lymph nodes the invasion things like that. But the real key to all of this and I apologize here for the slide that's just a bit off is that when you looked at the number needed to hurt and we all live in scenarios certainly at the Brigham I'm very proud of our surgeons they're very really talented but nothing goes without risk. And so when you actually asked what was the number of major operative complications and hurting a patient it was one in 49. If you considered surgery for benign disease and the excess morbidity it would bring as another harm it was one in 13 patients. So there was a conclusion to be drawn here which is that amongst an older population who had frequent comorbidities perhaps only the higher risk sonographic finding should lead to further workup including even an FNA. You could arguably safely simply observe those other nodules. Let me come to that third example in support of hemothyroidectomy or less surgery. Well I'll just show you two systematic reviews and meta-analyses as to why hemothyroidectomy really in the last 10 years has dramatically increased in terms of incidence in comparison to near total thyroidectomy. And the first issue is this when you look actually at surgical risk it is much safer to have a hemothyroidectomy than it is to have a near total thyroidectomy and you see that here in them in the systematic review as the diamond here is to the left of the value one. But when you think of effectiveness in particular here we're going to say disease recurrence. This systematic review in the British Journal of Surgery showing that it's equitable. So obviously we will always take the safer approach when the outcome is essentially equivocal. If I take that one step forward the question that is routinely increasingly asked is what if we have biopsied a nodule it is cancerous it is small it appears intrathyroidal and low risk. Do we really have to do anything. Is there is there actually an option of watching these patients in a non-operative fashion forward. And the answer is probably yes. First the data here out of Japan a lot of credit to Ito and his colleagues is published now over the course of the last decade. All of the initial work was done with micro papillary carcinomas those that were one centimeter or smaller but essentially showing a very high rate of safety in doing this. A small population will grow or progress. But the key to all of it is even in that population that then does get surgery and treatment it appears that that later so-called rescue surgery is equally effective at that point. To be provocative and push that even further we just published this in the J.C.E.N.M. just this year. Ben Altshuler was our first author. Thanos Bikos was a co-author. In this unique large-scale cohort that we've been following for 30 years there are unique patients who opt out of the traditional standard of care or surgery or whatnot for various reasons. Some is personal choice others is because of those comorbidities. But we looked and found this cohort over the course of about 20 years there were about 69 patients either who had biopsy proven disease or biopsy suspicious disease but the disease was large. It was between one and four centimeters intrathyroidal. All of them chose non-operative watchful observation. Now I grant you this is highly selected, but it's definitely food for thought because over the course of four years to follow, there was a 0% mortality that was disease related, a 0% chance of distant or metastatic disease. It was one case that appeared to progress and apparently on biopsy again was a poorly differentiated carcinoma. Now these nodules did grow as you would perhaps expect from a malignant process, but over the course of several years, even slightly higher and larger disease that followed conservatively seemed to be quite safe. So there are de-escalating strategies. When you think of what the ATA Clinical Guidelines Committee will be focusing on, it is going to be these types of clinical interventions because we realize if you can now identify the low risk sonographic patient, you're likely to reduce the need for much else by almost a third or what about that older group in whom we're going to perhaps only look for higher risk disease because they're quite sick. You can reduce a lot of unnecessary and risky surgery or perhaps in those that we choose less intervention or watchful intervention, we're going to reduce surgery even more. This is clearly what's happening and this is going to be foreshadowed in these new guidelines that we're just watching the pendulum swinging trying to find that perfect balance, right? The right treatment, the right patient, the right time, arguing we probably have been doing a little bit too much over the course of the last many decades. Let me shift now and go into the second theme that I think you will actively see put forth in the 2025 clinical guidelines and that is the power and utility of molecular understanding of thyroid cancer. We now have much greater ability to understand its importance, but more in particular how to use it toward beneficial efficacy. Now the starting point when I talk about molecular risk assessment of thyroid cancer, I think begins with the understanding that the BRAF V600A gene mutation, first identified by Ming-Xiao Jing in about 2005, was responsible for about half of all well-differentiated thyroid carcinoma. It was also perfectly predictive. There is no benign disease that harbors this mutation. That led to this assumption that if we could find the drivers of all thyroid cancer, well we'd be able to simply identify them preoperatively. That would be a good thing. But it became much more complex because, as you probably know, the second most common driver of mutations driving thyroid cancer are mutations in the RAS isoforms, H, N, or K. What's very different in that population is that they're not always perfectly predictive of malignant disease. In fact, about half of them will be found also in benign thyroid nodules and there should not be an assumption that all of them then will convert to malignancy. We just don't see that. The similar has been true with these other initial translocations, RET-PTC, PAX8, PPAR-Gamma. So it's complex. Nonetheless, the last decade has taught us that there's real value in molecular understanding of disease and the Guidelines Committee is going to certainly write about this quite a bit. When I talk about molecular cellular disease and thinking about thyroid cancer, I always like this simple cartoon because, to me, this is the basics of cellular biology that DNA is transcribed to RNA, is translated to a functional protein that does the job of that organ of that tissue, and there's a group of micro RNAs that are often inhibitory to that last step. But we've also seen the molecular machinery and the ability to use it transform and explode. And we now understand that mitochondrial DNA are critically important to herthal cell carcinoma understanding. There's a host of other so-called non-coding RNA that circulates, but yet seems to be very impactful on disease. And there's a host of other epigenetic markers, in particular methylation, that is also being looked at as a translatable target for understanding for us to use in the clinic. It's a real rapid expansion. So the upcoming ATA thyroid cancer guidelines will emphasize the different molecular options, but also how we use them towards disease in thyroid nodules and in thyroid cancer. And what do I mean by that? Well, I think many of you probably are most aware with the diagnostic use of molecular targets. Think of the Bethesda 3, Bethesda 4, the indeterminate cytologic category. We're pretty actively right now, we use molecular tests to help us determine benign or surgical disease. I think that's quite mature. As on the right here, I do think for very advanced disease, we've seen an absolute benefit and explosion of extensive genotyping for advanced disease so that we can target often a new TKI directly to that mutation and driver. What's been a little immature has been this concept of how to use molecular understanding of disease for prognosis. But it's rapidly advancing. In fact, if you look back at our 2016 ATA guidelines, when we talked about molecular understanding or analysis of disease for prognostic use, the answer was no, we're not ready to do that. And some would say, well, what about BRAF? Because Ming Zhao also published in 2014 that it was actually predictive of a worse survival. And the answer back then was, yes, in a univariate analysis, indeed it was. But the problem is in a multivariate analysis, it didn't help. In fact, you already knew from the histology, from the ultrasound, that there was a lot of lymph node disease often when they had the BRAF mutation, there was simply nothing that was additive from knowing that, so there was no need to test. Now things started to change. And in 2021, I'm not going to go through this, but the ATA anaplastic carcinoma guidelines clearly started to note the value of molecular understanding of disease and how that would be critical towards this advanced carcinoma. And that is clearly now the parallel theme that the Guidelines Committee, even for well-differentiated diseases, starting to grasp onto. That molecular prognostication, especially the more advanced your disease becomes, becomes helpful and becomes available now to us. There are numerous different buckets. I'll just give you some examples for the DNA-based scenarios. I want to showcase two publications from our group. The first is Theodora Papa, and she said, well, if I take the BRAF positive papillary carcinoma cohort, but increasingly we understand that there can be more than one mutations, what happens if I find that second mutation? In this case, a second mutation in the PI3K, AKT, or mTOR pathway. And what you see for the first time is that understanding, molecular understanding of disease, that double mutation independently predicts a huge increase in overall mortality risk. And the same would be true then in the RAS cohort. This was published by Thanos Bikas from our group. If you found, again, a RAS-positive malignancy and a second mutation, mortality significantly increased in a significant fashion in a multivariate model. While DNA prognostics are probably the most widely available testing that we will consider worldwide, I still think what we will find in the course of 5, 10, or whatever years ahead, is that RNA-based prognostics will probably be the most powerful application for us as it relates to thyroid cancer. Why can I say that? Well, it's not because we have yet the data exactly available to us in thyroid cancer, but we're also not the first ones on the block. That's the reason. If you look in the test here, primarily from the United States, but increasingly widely available across the globe, think about tests like Oncotype DX you may have heard of in breast cancer, Decipher in prostate cancer. Let's just go through these one by one. This is not thyroid cancer. This is something called GRID made by a company called Decipher that was looking at an RNA-based molecular test for prostate cancer, but what they were able to show is that this pattern, this RNA-based signature in this GRID, so to speak, was additive and increasingly beneficial beyond knowing the histologic phenotype, the Gleason score, et cetera, and it would predict mortality or the need for follow-up. The same thing with Oncotype DX for breast cancer, an RNA-based technology, this showing essentially what is your overall risk of breast cancer recurrence and even starting to talk about who would benefit then from chemotherapy or who would not, individualized prognostic therapy. This is important because that company, Decipher, that made the prostate cancer test has also purchased another in the United States company called Viracite, and they actually are in the thyroid cancer business. I suspect we'll see this kind of carry through ahead. There are many examples here in the literature. For time, I won't go through this here in great detail, but the prognostic opportunities that relate to molecular understanding of disease are front and center in front of the ATA Clinical Guidelines Committee. Because of questions like this, we would love to know molecularly who harbors a MEK signature because that predicts the iodine avidity, and so that predicts responsiveness to radioactive iodine ablation, but yet we don't have this yet. We also now have MEK inhibition that are increasingly in front of us to augment that uptake if needed. We would love to know this before an individual starts treatment. We also currently have no preoperative ability to adequately identify a NFTP, this low-risk kind of almost malignant signature, but that would be very useful then for the most limited removal that could be done, and you could make an argument the more we understand a molecular high-risk signature, a molecular low-risk signature, these are all going to be very important. So molecular prognostics are very much moving in front of us. I do think the 2025 thyroid cancer guidelines will still lead, of course, with the histologic diagnosis of thyroid cancer. They're going to still argue that we need the clinical staging data that we all are using currently, but equally important will be the molecular staging data because that's what comes together then for the discussion with the patient, and in particular then the individualized treatment. This is the process that is prognostic, that is individualized, and that is adaptive over time. That's what the guideline committee wants us all to kind of take forward. Prognostic information, of course, impacts care. I told you long ago that the initial question was everyone was getting a near-total thyroidectomy, but not anymore. The more we can understand overall risk, we're asking if any surgery is needed or if it is, how much? Same thing with radioiodine TSH suppression. Do we need it? For how long? To what extent? Everything carries a pro and a con, and increasingly what we haven't thought about but we will surrounds follow-up as well. How often to see someone back in the clinic? What testing to be done? When to discharge them? Finally, let me end here with just five minutes of kind of this, I think, cutting-edge kind of next step. So I told you early on that the association as a whole has a lot of debate ongoing about whether large-scale guidelines should be reproduced every five or ten years. It's a lot of work for the committee that puts forth the effort. It's a lot of time to dig in in a systematic way to all of the literature that we have. And yet at the same time, if you do it every five to seven or ten years in this case, you lose sight that advancements move forward every six, 12, or 18 months sometimes. So should we create more of a living document? I don't have an answer to that, but I do know it's very much front and center. And in that train of thought, let me share with you just how quickly things are advancing and what might be some of the cutting-edge next steps that we will see that will translate into the clinical care of patients in our clinic. So one of them surrounds single-cell analysis now of thyroid cancer, a very rapidly advancing field. And I like to lead with this question, which is, did you know, because I did not know up until I read the papers, that one cubic centimeter of thyroid cancer, a papillary carcinoma, just one cubic centimeter, harbors about 100 million cells. When you look under the microscope, they, to me, at least, look like follicular papillary carcinoma cells. That's what I see, and most of that slide is taken up with those cells. But that's not really what's going on. Within any given tumor, as homogeneous as it looks under the microscope, while there are tumor cells, there are stromal cells that are fibroblasts or mesenchymal cells. There's a host of immune cells. They're all playing different functions that are leading to individualized scenarios that prompt the next step and what's going to happen for this patient and this tumor. And in fact, let me show you the data by Pooh and colleagues. This was from Nature just three years ago. This was 11 patients where they analyzed papillary carcinoma. They did single-cell analysis on 160,000 cells. And based on the molecular profiling of those 160,000 cells, this is what they saw, that homogeneous one cubic centimeter of papillary carcinoma, it actually has maybe less than half thyrocytes. Most of what you find in there are immune-related T cells and B cells. Even if that's just an eye-opener, let's just look in particular at what they found just related to endothelial cells, that you can look at subpopulations, and understanding their molecular profile, you can follow the alluvial plot from left to right. Up on the top, if you have normal endothelial cells, they will typically evolve mostly to be lymphatics and then a little bit to be arterial and venous structures. But that's not true in the tumor. These vascular cells are now destined to become immature or lead towards the so-called tip of the endovascular structure, and they're acting very differently. We can understand that now with their genomic signatures, and that's leading to a much different understanding of risk recurrence and perhaps disease treatment. This is just one proof-of-concept study, but there's a second now that came out just last year in JCNI looking at anaplastic carcinoma and beginning to tell us why is it that we've always known anaplastic seems to evolve from papillary carcinoma, but then quickly becomes one of the most dangerous diseases. And it really shows here that on a single-cell basis, we understand there are two phases. The first is the genetic changes create an inflammatory phenotype, but over time, that actually devolves, and it becomes a so-called mesenchymal phenotype as the immune system also becomes intolerant and exhausted, essentially. 2024 is ripe and available with science being performed as it relates to the so-called omics, whether it's bulk RNA sequencing, single-cell sequencing, single-nuclei sequencing. Attack sequencing deals with those epigenetic changes. There's a lot there. The second cutting-edge area that is increasingly gaining attention is metabolomics. So if we've talked about DNA translated to RNA transcribed to a protein, et cetera, what we realize is that at the end of the day, it is then the actual job of that organ that is actually creating the phenotype in the individual. And if you look in particular at just the numbers, we have a lot of DNA. We have a lot of proteins that are generated. We have relatively few metabolites at the end of the day, but they really tell us what's going on within the cancer, within the patient, and that can be profiled. And so metabolomics is being profiled looking at these various cellular systems we all learned once in medical school and then long kind of forgot. But take this, for example, Ian Ganley out of Sloan Kettering and just a year ago and some data now coming out of our lab as well. This was just looking at herthocell disease, whether it be benign, mild, or advanced carcinoma, and they clearly profile quite differently. There's actively different things going on which can give us insight into the individual and probably will be something we can test on most patients ahead. So what's next? There's a lot. And I'll make sure I give time for questions here as well. And I don't know the exact release, but I do know that finally after many years and a lot of hard work by some great people on both of these committees, we will have active documents and I will bet that they will come forth for public release in 2025, two separate sets of guidelines, one on nodules, one on cancer. And so my summary on differentiated thyroid cancer foreshadowing the 2025 American Thyroid Cancer Guidelines. The summary take-homes that I would give you is this, I think it's very important we continue to acknowledge that most well-differentiated thyroid cancer is low risk. It's also readily treatable and it confers a very good prognosis. And in fact, individualized risk assessment is now more important than ever. In large part because we probably were over-treating so many patients before. De-escalating intervention is the active issue in front of us. How do we do that? Perhaps less FNA, more reliance on ultrasound, less surgery, perhaps not considering radioactive iodine, maybe a little bit less TSH suppression, things like that. We're trying to find the subgroups to apply the right treatment to the right patient at the right time. The second theme, as I mentioned, is that molecular analysis of thyroid cancer is important. It's certainly not required in all cases, especially in low-risk disease. But it is increasingly considered, especially as the disease advances. And that's in large part because it allows you the individualized understanding of what's going on and prognostication that flows from that. That is what's new in molecular world. It's not as much diagnostic or advanced treatment. Those I think are pretty established. But the individual prognostication is moving forward. Obviously, I tempted you and tempted myself with just discussing the cutting edge of thyroid cancer and really what I think though comes forth so frequently now in front of us. It's a very active moving area and hence the reason we may see a living document into the future. Most importantly though, I just want to thank all of you for your attention, the chance to come to Dubai and speak to you here today. More than happy to take questions as well.

ATA guidelines

thyroid cancer

precision medicine

molecular diagnostics

personalized treatment

active surveillance

living guidelines