The majority of thyroid cancer represents low and intermediate risk disease. Thyroid hormone suppression and other related issues may require coordinated care between providers. Given the indolent nature of these tumors careful consideration of the risks and benefits of treatment is necessary. This webinar will discuss and review common scenarios and highlight points of care relevant to the management of these patients across their care team.
Twitter @PennMDForum Management of Thyroid Nodules | Penn Medicine Thyroid Cancer, Nodule Management and COVID-19 | Penn Medicine Breast Care and Imaging During and After COVID-19 In South Jersey Hello, everyone. Welcome to the CMI. Approved women are sponsored by the Endocrine Disease Team at the A C. C. Here. Ahem is, um today we'll focus on the evaluation and management of patients with low risk, our cancer. Basically popular thyroid cancer, the most common histology. My name is Ben Kuperberg. I'm chief of Enneking Division at Mental Hospital. I'm joined by four colleagues who's disciplines represent the multidisciplinary collaboration essential for care of this patient population. First in the technology is Dr Susan Mandel, chief of the Division of Technology, Diabetes and Metabolism. A pen, our immigrant surgery colleagues, Dr Heather Walked Album from Pathology. We're joined by Dr Jalal Jalali and from nuclear medicine, Dr Dan Prima, chief of the nuclear medicine section. Together, our goal is to define and review the approach to a patient found to have low risk their cancer, which is both evidence based and patient centered. Given the indolent nature of these tumors, careful consideration of the risks and benefits of treatment is necessary. This webinar will discuss and review common scenarios and highlight points of care relevant to the management of these patients across their care team. Our objectives, say, or to recognize the attributes of Lois thyroid cancer to use patient factors to identify the extent of surgery, including unilateral versus bilateral third activity. To identify the clinical parameters that required for decision making around I won 31 therapy and to describe a patient centered approach to surveillance, including TSH targets, ultrasound imaging, Sarah globulin and dynamic risk stratification. This webinar is live and will be conducted as a panel discussion at any time during the weapon are you can submit questions by using the chat box. Please send all we have reserved 10 minutes for questions at the end of the session. This session is being recorded and a link will be available for future listening. We will also provide a pdf head of P slides. So to start with, let's ask, what is low risk dark cancer by which we mean low risk PTC or Pepe Lothar Cancer Susan, If you could please take us through this right, Good morning, everyone. And it's a pleasure to be here with you again with your person cancer center. So when we're talking about risk, um, we're generally talking about their two systems that we can use, and there's, um someone has a diagnosis of cancer. We talk about the risk of survival. So life and death. Unfortunately, as you heard Ben saying, the preamble of your most thyroid cancer is very, very low risk. We will be having a future webinar about higher risk thyroid cancer. But that's one type of risk. But the second type of risk, which really is relevant to the vast majority of our thyroid cancer patients. For currents on, we used to different systems to predict thes so for survival, we generally use the A J. C C tnm staging, where the eighth edition on for recurrence. We use the 2000 and 15 American Thyroid Association, which will be abbreviated as a t. A risk of structural recurrence. So let me show you how this work. So when we're talking about survival, we used the H A. C c eighth Edition. Thyroid cancer is the only cancer were. Really. Age is the first defining factor in putting our in classifying our patients who are diagnosed with thyroid cancer in two stages. So if you're 54 younger, you can't even be stages three or four. You are only stage one or two, which for most cancer. Stage one and two are considered low risk, and Stage one is basically any patient with disease confined to the neck. And Stage two is any patient 54 or younger who has metastatic disease. So a patient who's 54 or younger with papillary thyroid cancer cannot be in the higher risks of for survival of stages three and four. Now if you're 55 or older, which some of us are now, um, it's a little bit different, but stage one and two really refer to disease in the neck. So Stage one, if you're 55 or older, is when there is simply a thyroid all tumor, maybe with a little bit of invasion into the parathyroid adipose tissue. But without any positive lymph nodes and stage to remember, Stage two is still considered. Low risk is local regional disease, where the tumor is more aggressive, maybe invading into the muscles but not invading into the vessels or trachea. And it's any lymph Edin apathy, metastatic lymph retinopathy. So disease confined to the neck in our older patients and disease confined to the neck for stage one in our younger patients. But metastatic disease is in stage two, so one and two are generally considered low risk for survival. So what does that look like? Well, if we look at survival so life and death divided by stages you can see for stage one and stage to the survival is really excellent. Now it turns out, as I said, most of our patients with differentiated thyroid cancer are on stage one and two. Stage one has very, very high 10 year survival rate over 98% and Stage two has a very good survival rate 94% but a little bit lower on. The key factor is if you removed the young patients with metastatic disease on you. On Lee, look at those patients for diseases confined to the neck. You can see that the survival is much better. So now let's look at recurrence. So that's the other type of risk. So we just looked at life and death and survival. Using JCC eight for recurrence, we look at the American Thyroid Association risk of structural disease, and this is something that we can Onley determine after surgery when our pathologist gives us the final pathologic diagnosis and this is divided generally into three categories, with a slight subdivision in the low risk category. But we're talking about recurrence or the likelihood that cancer returns. So we have a low risk group where the risk of recurrence is less than 10% and shown on the right side or all the pathologic features that have been associated with risks of recurrence. Remember, this is not survival. Less than 10%. 1 of you submitted a question about eight millimeter tall sell popular carcinoma that had invasion Justin to parathyroid, all soft tissue. This would be considered low risk in the absence of vascular invasion, so you can see all of these pathologies have a less than 10% chance of recurrence on. You can even potentially branch off some that are less than a 5% chance of recurrence. But then, as we go up as the pathology gets more aggressive and Jihua will be discussing about this some more as we get metastatic lymph nodes, more aggressive pathology and vascular invasion, the risk of recurrence increases on as we get even more aggressive pathology, generally with larger lymph nodes, higher numbers of lymph nodes on extension outside of the thyroid in our young patients, the risk of recurrence increases to about 30% and you can actually put these together. So if you if you combine the risk of recurrence with the A J. C C eight stages for patients who are less than 55 let me show you what that looks like. So here we have all of our Stage one patients less than 55. So remember patients less than 55 stage one disease confined to the neck, but that could be an eight millimeter micro papillary carcinoma. Or it could be a four centimeter papillary carcinoma with many positive lymph nodes on. What you can see is that survival differs so that if we look at our stage one patients and we stratify them by their risk of recurrence by the American Thyroid Association, you can clearly see when you're looking at survival that those patients that have a high risk of recurrence do You have decreased survival, and it even depends a little bit about your age. Even if you're less than 55 so you can see high risk of recurrence does does impact survival, and especially for those patients between 45 55 who have disease confined to the neck. Remembering that high risk is where there's lots of vascular invasion, lots of larger metastatic lymph nodes, gross extra fire, it'll extension and some of our more aggressive mutations. So even in what we consider Stage one, we can begin to break out. Ah, higher risk group. So what, then, is low risk thyroid cancer, where overall stage one and stage to have great survival rates and very low mortality rates. But within Stage one and two, we can modify and better understand those survival rates by modification with the risk of recurrence, so that mortality is higher in those patients Were diseases confined to the neck if they're in the slightly older part of the stage 1 45 to 55 versus under 45 and importantly, if they're in stage two. If you remember, the younger patients with distant metastases are the ones that are going to have lower survival rates than the older patients. Stage two, where disease is confined to the neck, so that's for survival. But remember, even if your stage one or stage two with the low risk of mortality, you can still have an intermediate or high risk of recurrence. And this is going to be important as Dr Prema is. Dan begins to talk to you about radio event. So then I turned it back to you. All right, Susan, thank you very much for the intro. That was really great. Eso Let's supply all that information Thio Case study and talk about a patient. We have a 53 year old female who has undergone an ultrasound guided F N A for right sided 3.2 centimeter thyroid nodule with the cytology diagnosis of popular thyroid cancer. Bethesda. Six. Importantly, the fired ultrasound did not note any abnormal cervical of notes. I have referred her to Heather for surgery. So, Heather, if you could please take us through your decision making process as you discuss the extent of surgery in this situation, including your approach to look, that's eight. Well, thank you so much. It's such an honor to be here this morning. Happy to take move to the next slide, please. So when we talk about the surgical approach to low risk thyroid cancer, all of surgery is informed by the anatomy of the patient, just a za brief refresher. The thyroid is a butterfly shaped gland that sits in front of the trachea. And there a couple of structures that were very careful about during surgery main structures that we really strive to protect, our the recurrent laryngeal nerves and those run poster to the thyroid on the either side. Each recurrent laryngeal nerve serves to innovate the vocal cord on each side, and we routinely used neural monitoring. Thio protect the recurrent laryngeal nerves. Help identify them at an early stage in the surgery. Not showing on this diagram are the parathyroid glands. As you know, everybody has parathyroid glands. Typically, it's four glands and two on each side on work very hard to identify those and to brush them off during the at the time of surgery. Eso If you advance the slide, you can see that there's a couple of these structures. Allow us to think about, um, discussions with the patient about doing half or whole so bilateral or a total thyroid ectomy versus a unilateral or a thyroid lumpectomy. And when I discussed this option with patients, I talk about the Inter operative, the Peri Operative and then the lifelong factors, which contribute to this decision making. Clearly, there are some scenarios in which the decision is very easy. So for large tumors tumors with aggressive features such as gross invasion of the structures around it. So anything greater than four centimeters they're going to require a complete or total thyroid ectomy for patients who have concerning lateral neck lymph nodes. They're also going to require a total thyroid ectomy, and this is because we know that they're going to anticipate radioactive iodine. I jumped a adjuvant therapy for patients who have micro cancer. So less than one centimeter, unless there's other patient factors, will typically recommend a low back to me. But for patients with between one and four centimeters in size, like our case study, we have the option of doing half or whole. So a total thyroid ectomy or unilateral. So in terms of the very short term factors that I discussed with patients, intra operatively, we dissect around both recurrent laryngeal nerves when I do a total thyroid ectomy and just around one nerve when I do a unilateral thyroid ectomy and clearly those are very low risk and again we preserve them using neural monitoring. However, there's When you operate around to nerves, there's slightly higher risk than there is around one nerve. When I operate around all the parathyroid is they'll get a little bit bruised or ECOMOG IQ during surgery, and so, typically for those patients, they will require some temporary calcium supplement. Our protocol here is to send everybody home with some aural calcium supplement for about two weeks after surgery. For a patient who is undergoing unilateral surgery or low back to me, they only need, uh, to be dissected around to parathyroid. So no matter what happens, the other parathyroid zehr preserved and therefore they do not need routine calcium supplement after surgery. The risk of having a hypo calc mia permanently is extremely low, but and so therefore, I don't consider this a lifelong risk in terms of the peri operative considerations. There's really no risk, obviously, of needing second surgery completion thyroid ectomy If you've taken the whole of the gland on the first surgery, and for patients who have done a unilateral thyroid ectomy, there is the possibility of requiring a completion thyroid ectomy, depending on their final surgical pathology, and my colleague Dr Jalali will be covering some of the pathology factors. And then clearly the biggest consideration for many patients is that for patients who have had a total thyroid ectomy, they will have permanent hypothyroidism and therefore require leave a thigh rock scene or other thyroid hormone supplement. Lifelong. For subjects who undergo just a unilateral thyroid lumpectomy, they have a low risk of hypothyroidism. This is TSH level dependent. I typically quote people 15 to 30% chance if their TSH is in normal range. But there's excellent data from the 88 guidelines and others to give you ah, more granular estimate based on the preoperative TSH next slide, please. So in other than the an Atomic factors, there are a number of different patient factors which influence the extent of surgery theme. The presence of contra lateral modules, the presence of pre existing hypothyroidism with dependence on thyroid hormone patient risk factors. So I take into consideration the entirety of the patient, meaning that if they have other risk factors for bleeding, they're on a blood thinner. These are all important things that we discuss as well as their family and their personal history. So a patient with a personal history of radiation has clearly a different profile than a patient who has no history of hedonic radiation, their pot, their ability to be compliant with medications for this, maybe variable and the risk for general anesthesia. Because all of these procedures are performed under general anesthesia. Also, our level of concern for aggressive disease based on their image ing and their anticipated surveillance needs. And I do want to emphasize next slide, please, that this is shared decision making. And it's shared decision making, not just between the surgeon and the patient, but also between the surgeon, the patient and the endocrinologist on. We are all a team, and we approach this in a team fashion and therefore find that this is is really ongoing discussion that incorporates the patient. Factors are overall picture, and there are goals for their care. Okay, in terms of how the data that drives our decision making in, uh, for a lumpectomy versus a total thyroid ectomy, there is extensive data on did you can continue advancing. There's been a number of different papers which have showed a equivalent survival. Next slide, please eso. This comes from a large Siris of approximately 25,000 patients looking at the survival outcomes with a total thyroid ectomy versus a low back to me and the survival curves here actually track completely together and cross multiple times. Uh, actually, the size of tumor is a better discrimination. So sizes 1 to 2 centimeters versus a 2 to 4 centimeter that you do see some slight difference in survival. And these are all subject factors which I discussed with patients at the time of their preoperative evaluation. Right, Well, past things over to my colleague Dr Jalali. Alright, so thank you very much harder. That was wonderful. Eso our patient in this case, based on the lowest features, has undergone a right back to me after a third discussion, and the pathology is now available. So, Jalal, if you could walk us through the features of low risk pathology findings on the final pathology would lead to more concerned for completion. Productivity indicated to facilitate by 31 therapy. Certainly. Uh, so thank you, Ben, for the introduction. And also thank you, Susan and Heather for setting the stage to talk about pathology. So, uh, I'll be talking about how to assess, uh, thyroid cancer and what it means from a history pathology standpoint for thyroid cancer to be low risk. So when we're talking about thyroid cancer, uh and, ah, low risk thyroid cancer. We're mainly talking here about differentiated thyroid cancer carcinoma, so popular thyroid carcinomas or follicular thyroid carcinomas. We're not talking about poorly differentiated thyroid carcinomas or anaplastic thyroid carcinomas, which are naturally more aggressive and high risk. Um, specifically, when we're talking about popular thyroid carcinoma, we're mainly talking about the classic and particular variants because some other variants can be more aggressive and associated with aggressive features that they're as vascular in Beijing or extra Thai royal Extension grows except by rural extension. And when we're talking about follicular thyroid carcinoma, we're mainly talking about the minimally invasive follicular thyroid carcinoma not talking about the widely vascular invasive, uh, follicular thyroid carcinoma. We're also talking about thyroid cancer that is confined to the thyroid and without grows extra Thai Royal Extension, uh, without many lymph nodes, especially lymph nodes and metastases that are less than two millimeters on again without extensive vascular in Beijing or no high grade risk features, which I'll show pictures and talk about a little bit more. So here is an example of papillary thyroid carcinoma. You can see here that it's very nicely confined to the thyroid very nicely, uh, encapsulate or while circumscribed. You can see here some residual uh, by, uh, that is not involved by cancer on. When we look at the nuclear features of this humor, it's indeed a popular thyroid carcinoma with nuclear clearing groups, inclusions all the features that we consider for papillary thyroid carcinoma Note that this humor is also forming follicles on without any popularly. But in order for such a humor to be called popular thyroid carcinoma, nowadays we do have to have some popularly or some extension to the surrounding thyroid because otherwise it would be even considered a lower risk humor, which is nowadays called an FTP on a low risk thyroid cancer, can also be a popular thyroid carcinoma classic variant, where we can see here that the humor is forming Nice Populli and you can see here that there are nice. So MoMA bodies, which are basically did classified tumor tips that lost their blood supply. Uh, multifocal ality eso. If you have a differentiated, popularly thyroid carcinoma, that is more than one in the thyroid that would still be considered low risk. So multifocal ity. As long as the tumor is differentiated without any high risk speeches, it will still be considered the low risk. Uh, humor eso. What about extra Thai Royal Extension? Uh, it's very important to differentiate between minimal or microscopic extra Tyrell extension that you can see here on the left hand side compared to the gross extra Tyrell Extension with invading into the skeletal muscle that usually is detected intra operatively by the surgeon. And we correlate really well with our colleagues, like Heather and other surgeons, to see what they saw intra operatively and whether or not the humor is invading into the surrounding tissue. But a hint for that when we look at things under the microscope is thean Veii Asian off the surrounding skeletal muscle. As you can see here on this tumor, is actually even involving the margin. So if the humor is on Lee invading the surrounding soft tissue like adipose tissue, that that does not change the T stage anymore in the new a GCC, whereas the gross excess federal extension will do, uh, lymph node metastases. If it's a small lymph node, with a small, metastatic focus less than two millimeter that is still considered low risk, however, if the metastases is big and it's more than three centimeter off there, more than five lymph nodes that could be considered intermediate or even high risk thyroid cancer some aggressive variants that I mentioned earlier, especially if they're associated with, like other aggressive features, many lymph nodes, large lymph nodes are gross. Exxon Federal extension can be considered high risk. So here's a tall Sal variant where the tumor cells cytoplasm is taller than it is wide, and those can be associated with gross extra title extension in more than 50% of the cases. Hob nail variant. As you can see here, the cells are Some want this cohesive and kind of falling apart and almost resemble a nail on a wall. And that's why we call it a hob nail variant. And then the kilometer sell variant, which is can also be associated with vascular in Beijing. As you can see here, the tumor nuclei are quite elongated. They're dark and, uh, they can be aggressive. Uh, vascular invasion in general is also considered the high risk feature, so you can see here. These are folksy of vascular invasion, and if you see that in a popular thyroid carcinoma that can be considered the high risk and also in follicular thyroid cancer but in particular thyroid cancer, we try to differentiate between focal vascular invasion and a next ensign basket. But in Beijing, and usually you use a cut off of more than three folks side. Some other high risk features is the so called high grade paper retired character, and that can be associated with, like extensive necrosis or para neural in Beijing. And then, as I mentioned, if it's not a differentiated thyroid cancer, then it's not a low risk. So here's an example of a poorly differentiated thyroid cancer on a plastic thyroid carcinoma, and I'll switch over Thio. And for now, all right, thank you for walking through. Much of all that was really helpful. I'm going back to our case. The final pathology indicates a classic PTC with Capital ER invasion, a low risk apology. So the next step in decision making with our cancer is whether I went 31 therapy indicated, which would require a composition fired activity and not because of concern for cancer and the contra level low. But because Total third after me needs to be done in order to facilitate Island 31 as was already discussed by Heather. For patients who have been inter thyroid all TTC less than four centimeters, that is a low risk for recurrence. Describing Susan, look back to me alone with advice. So now, Dan, can you please walk us through your thought process with regard to when I went 31 therapy would be indicated, even if not for this particular case. Sure, and thank you very much for the introduction is great to be here and thanks to everyone for being up early toe here about this. So we really want to think about why, why we're going to do radio iodine therapy. And we think about radio iodine as it's really the first radioactive drug and wide use, still the most successful one. And it really can't help patients with iodine avid thyroid cancer in terms of therapy of patients with known advanced metastatic disease. And so we want to be aggressive in those patients. But that's a pretty small subset, as you've already heard of all commerce in differentiated thyroid cancer, and the vast majority of patients do really well. So the most common indication for therapy with radioactive iodine is what we call ablation. You're just trying to kill off whatever thyroid tissue remains in the neck. And most of the time that's normal thyroid tissue, not thyroid cancer. And it's really helpful for monitoring purposes to make the fire globulin undetectable. It makes us feel a lot better as clinicians seeing that nice undetectable on the fire globulin. But it really, um, in some cases doesn't make anything different for the patient at all. And so we want Thio. Remember that? So when we're weighing the risk versus the balances, the benefit is it's important. But it's not huge in patients at the lowest risk of recurrence. So in patients at low risk of recurrence, we don't need toe Blake them because we don't need that enhanced monitoring capability. Adjuvant therapy, which has been shown in many cancers to be effective, so treating patients after a curative intent resection to reduce the rate of recurrence make sense. The data for that and thyroid cancer is not great, and a lot of that is just because radioactive iodine came along at a time when clinical trials were not what they are now and it's become standard of care. So we'll never probably be able to randomize patients to, um, therapy versus not therapy. So what we have is case Siri's where some patients were treated. Some weren't. But there are clinical decisions to treat or not to treat. And so the data is not incredible. Next slide, please. So the bottom line is we we do. Have you saw this graph already from the A. T. A. On basically some of the things that raise your risk. And there are a lot of things that you can see in thyroid cancer that for any other cancer, is going to really get your Spidey sense is tingling and make you really nervous. Patients with positive lymph nodes, multifocal disease, sometimes big tumors, and you can have those things and still be at very low risk, especially if it's a young patient. So the things that really start toe make me think. I try to reverse it in thyroid cancer and try to think every patient's low risk unless they have some features of high risk and the things that start to make me nervous or extra thyroid Alexe tension, lymph nodes that have extra nodal extension and really extensive vascular invasion. Things like capsule er invasion really don't mean as much because it's still something that the surgeon was able to remove. So if if everything is within the thyroid and staying in the thyroid, those air generally lower risk, even if it looks like a big tumor next slide. And so the vast majority of patients with differentiated third cancer do well, and I really I I hope that you take away, ah, willingness to lean towards less rather than more aggressive therapy with the caveat that you do occasionally see a needle in the haystack. And you do see patients who have thyroid cancer that will ultimately be the cause of their death. And so don't ignore that. So treat every patient like they're, you know, lean towards the lower risk setting. But if a patient is behaving badly, recurrence early, Um, they you respect some recurrence. They recur again. Present with metastatic disease those of the patient that you don't want to say, Oh, thyroid cancer is a great cancer and and patients don't die of thyroid cancer. If you find the patient that does treat them aggressively. But don't treat everyone aggressively, just in case they might be that needle, they'll they'll declare themselves. And you have time to learn which one is which, and in the meantime, leading towards less aggressive. Okay, all right, Thanks, Dan Askew can all see the importance of having a team approach. Thio Patients is critically important management, even if the cases are low risk. Um, I really can't say enough. How important is to be in constant communication with all of our colleagues, and that's what will ensure the best care of our patients. So, Susan, for our patient with lower start cancer, which didn't require completion surgery or I 1 31 what would be the risk of with parents, and how did you follow them out? Thanks. It's a really great question and assess whether showed you this concept of love back to me really came about. Since papers from 2011, 2000 and 12 and was first highlighted in the 88 guidelines in 2000 and 15 on actually some really good health services, research has shown that since 2000 and 16 the rate of low back to me has increased significantly over thyroid act to me as surgeons and endocrinologists or finding the following the guidelines. However, for us, it's a little challenging because you heard Dan mentioned that word. Thyroid globulin. So thyroid globulin is a protein that's only made by normal thyroid and by thyroid cancer. And it's sort of RPS A of the thyroid cancer world, so that if someone has had bilateral thyroid surgery by a good surgeon, even if they haven't had radio iodine, the thyroid globulin should be less than one on if they have had radio iodine. The thyroid globulin is generally undetectable, but the challenge is that when you have a lumpectomy, you have half of a normal thyroid in place. And unfortunately, although, um, the initial guidelines for using fiber globulin in the in the 2000 and 15 document said that the thyroid globulin should be less than 20 or 30 after a low back to me, that hasn't been shown to be true. So what you'll see in the 2021 guidelines is that thyroid globulin is probably not helpful in the follow up of patients with low back to me because we know that many benign thyroid diseases are associated with elevated thyroid globulin, including nah, JAL's benign modules as well. So we actually kind of have to remove thyroid globulin from our follow up strategy. We'll talk about that more with the next patient, but we can talk about TSH. So one of the golden rules, you might say prior to the more recent guidelines, was that patients with thyroid cancer should be maintained with a low TSH because TSH stimulates thyroid cancer to grow. But if a patient has had a lumpectomy, as Heather said to you, one of the advantages is that hopefully you may not need to take thyroid hormone if you're preoperative, TSH was and let's say, less than two. And so, if you actually look at whether TSH Suppression is helpful in preventing recurrence in low risk thyroid cancer patients after lumpectomy, the answer is no. So looking at almost 500 patients followed for a median of over eight years, whether they received TSH suppression to keep the TSH less than 0.5, or whether they received no TSH suppression, and also the TSH was in the normal range up to 4.5. There was no difference in recurrence rates. So here we're talking about recurrence, not survival, but absolutely no difference in recurrence rates on I think the hesitancy, you can see it right there. No difference is that in the eighties guidelines from 2000 and 15, they did recommend that the TSA should be kept in the normal range. But less than two on this may actually change in the newer guidelines because there really aren't data to say at this point. Whether a TSH between two and 4.5 versus less than two makes a difference in our lumpectomy patients. So it's obviously ideal if the TSH is in the normal range, but less than 2 to 2.5. But there's absolutely no data that would say that keeping the TSH below normal is going to change recurrence rates after lumpectomy on Remember, we can't really follow thyroid globulin, but there is something else that we can follow, and that's ultrasound. So when recurrences do occur now, Heather showed you a graph like this that was for survival, showing that life and death is not altered by lumpectomy or thyroid ectomy. um, what I'm showing you here is recurrence or the likelihood that local regional diseases detected after low back to me or thyroid ectomy and this is from has been shown in at least four studies. And I'm showing you here one of the graphs from Doctor Kim that looks at recurrence rates with low back to me and thyroid ectomy in patients with tumors between 1 to 4 centimeters. And some of these included lymph node metastases that were micro metastases. As was explained to you by Jalal. If you have a lymph node metastases less than two millimeters, that is not considered high risk, and it turns out that when you look at where these recurrences are, the recurrence rates are about 49% in that 5 to 9 year period, and they're in their neck. And they do not differ in our patients who've had unilateral versus bilateral surgery. So if you look at the timing of recurrences, probably about 50% of recurrences will will occur in about five years, and some might occur a little bit later. But there's no indication to do ultrasounds potentially more frequently, remembering that all patients should have undergone that preoperative ultrasound to look at their lymph nodes prior to surgery. So since we can't use thyroid globulin, we can still use ultrasound to look at the thyroid bed, to look at the lymph notes and to look at the contra lateral lope. And the first ultrasound could be done in 12 to 18 months. And if that looks fine, given the time course for these recurrence, which media and it's around five years, you could probably repeat the ultrasound at five years. And you do not need to be doing annual ultrasounds in these patients. Unless, of course, something is found at that first ultrasound. All right, thank U S. So let's modify the case that we have of our 53 year old patient. So as for F, any of the right power nozzle revealed PPC. But now, in this instance, pre up ultrasound imaging demonstrated to suspicious rights lateral lateral neck book notes F in a sampling of one of these, which measured 1.7 centimeters, was also positive for PTC. Now, please remember that whenever an ultrasound exam of the flower it is done, it really must include evaluation of lateral cervical Internet chains So if you get a report from the radiologist that's describing thyroid but does not make any mention of notes, make sure to review with them because really can't make a good decision about clinical management without knowing about the possibility of concerning Lippman's so Heather with this new, you know, changing the case. How much that change your pressure from surgery? Great, Thank you. Before I address the new case, I think I'll double back around. There've been a number of questions in the Q and A. A box, and I think the first one pertained to our first discussion. Eso doctor below should said, How will you pre operatively risk Assess a case of a 40 year old woman with a 0.7 centimeter suspicious thyroid nodule within FN. A diagnosis of Bethesda, a five molecular positive for be Raph and Turk promoter mutations with jai alai lick frequency. Would this still be classified as pre operative low risk? And with the surgical approach change, I think this is an excellent question and highlight some of the challenges that we face when we try to apply guidelines to individual patients in particular here, the size of the tumor is actually conflicting with the histology with a B raffin, a Turk promoter mutation. We would classify this as an intermediate risk cancer despite the size. And Susan will frequently remind us that our multidisciplinary meetings that the histology will drive tumor aggression prime and that every large tumor started out as a small tumor. So my discussion personally with this patient is that they have an aggressive histology and that we would consider doing a total thyroid ectomy versus just the unilateral thyroid ectomy, which would be mandated by the size. However, if the patient wanted Thio pursue Ah, unilateral die, reject me a thyroid lumpectomy Think that would be reasonable? Um, knowing that the salvage therapy meaning a completion thyroid ectomy, is generally very safe and very well tolerated and could be formed performed at a later date. But as with any other of these decision making, particularly in these ambiguous cases, this is a shared decision making and something that I discuss both with the patients and the referring endocrinologist. Eso I'm gonna turn back to the case study. So this is our original 53 year old female. However, instead of having just the isolated right, 3.2 centimeter thyroid nodule. She also has suspicious lymph nodes in the lateral neck. If you advance this slide, just a brief reminder about the cervical lymph nodes levels is that the level six lymph nodes or the central neck lymph nodes are located in the area of the thyroid. And that's between the Eastern applied, um, asteroid muscles bilaterally. So that's highlighted in purple. Here, the level seven lymph nodes are continuation of the level six but going down in fear to the clavicles. When we have a position, patients for surgery with neck extension will actually often bring level seven up into a level six. So I see those as a continuity. The lateral neck are the levels 23 and four. So in the area of the stern applied um, asteroid and then the post your neck is level five supposed your to the stern applied um, asteroid, and it is unusual, not unheard of, but unusual for Level five to be involved in papillary thyroid cancer. Most commonly, we'll see local regional spread in level six and then continuous spread into levels 23 and four toe feel advanced. The slide. This'll is a patient of mine. Um, this was a young woman who had actually self palpate id a right thyroid mass and on ultrasound actually had bilateral thyroid masses. So if you advanced the slide, thes two cuts are slightly better images of her bilateral tumors. The dominant one was on the right, and then the smaller one was on the left and a few advanced this slide. And this really highlights what Susan had mentioned, which is the extreme importance of needing ultrasound of the cervical neck nodes and because it changes the diagnosis. So based on her thyroid image ing, she would need a total thyroid ectomy given thes size of thes. Nah, Jules, I would have performed a central neck lymph node dissection as well. But her ultra stenographer, who Dr Langer, who's actually are ahead of thyroid ultrasound here, called me on the day of her ultrasound and said, Look, she's got lateral neck nodes on the on the right side. And so we knew based on the ultrasound appearance, even before the biopsy came back. But she was gonna have lateral neck disease. However, we did obviously wait to see the biopsy results before planning her surgical approach. So for lateral neck lymph nodes because we know that there is contiguous spread and that level six will definitely be involved if you have evidence of level. Level 23 or four always plan to do a total thyroid ectomy and then bilateral central neck lymph node dissection, meaning taking level six bilaterally and then performing a modified radical neck dissection on the hips. Lateral side. So where you have biopsy proven lymph node metastases and a next life, please. If you note here in this image the abnormal note here is immediately in posterior to the oma high, you can see the oma hide passing a just anterior to the node, the jugular vein and the carotid artery. So this is a level three low level three high level four. Um, note. I always take the compartment of the affected notes and then the adjacent compartment. And so here. Given her extensive disease, I definitely needed to do three and four. I also opted to do, too, because I had some high concern for this patient. Eso This is called a modified radical neck dissection. The radical neck dissection would be to remove the jugular. The Vegas and the Senate. Clyde I'm Asteroid, and that's really fallen out of favor and head and neck surgery. Except for the most abnormal cases. There was actually a very interesting quote back in the 19 sixties from head and neck surgeon who said the radic ality of the surgery should be directed against the cancer rather than against the neck. And so now we preserve the jugular vein. We preserve the vagus nerve, we preserve the muscle, and we only take the lymph nodes. A selective lymph node dissection would be to take less than levels 23 and four on DNA. That is a uncommon surgical approach for us. So for our case here for this woman with three centimeter tumor and biopsy proven lymph node metastases, my surgical recommendation would be a total thyroid ectomy, a bilateral central neck dissection and an IPs lateral modified radical neck dissection. Hello, Thank you so much for walking us through that and give us your You're approaching about process. So after surgery, final pathology was a 3.2 centimeter classical PTC with no vascular invasion, 5 12 metastatic lateral neck lymph nodes largest measuring 1.2 centimeters and three out of five. Metastatic Central Next book notes The largest metastatic lymph node measuring once in years. So not the micro lymph node metastases. A subscriber earlier by Jalal. Although this patient would be considered stage one as discussed by Susan, this patient is also considered to be an intermediate risk for occurrence. So, Dan, if you could please tell us why 1 31 30 in this scenario. And if you also talk about preparation as well as risks, sure. And so this is a patient who is starting to hit some of those markers for higher risk disease where now I'm 31 is indicated, but still a long as there's no extra nodal extension, no extra thigh royal extension. This is a patient that can still be treated with that, a blade of intent therapy with the lowest effective doses, which I think still makes a lot of us a little edgy because we're just used to giving higher doses. But it is it has been shown to be effective, so I'm gonna get to that a little more on the next slide. But as far as patient preparation goes, we want accomplish two things we want the patients total body stores of iodine to be low on. We do that by following a low iodine diet. Um, and we used to go through a lot of rigor, moral, trying to come up with their own things. Now we just refer patients there to really excellent online. Resource is one is Thika, where they have this law. Iodine Cookbook. If you're patient speaks Hebrew, Japanese or Spanish, they could get a direct translation. Otherwise they could make do. And then the other one is one called lid Life lid for low iodine diet. And it's interesting they sort of take two very different approaches to the same thing. The Psycho one is basically starting with raw materials to make sure you're on a low iodine diet and a lot of cooking, which I think would be fun for patients in the covert era, since we're all experimenting in the kitchen with nothing else to dio lived. Life, on the other hand, went to look at prepared foods and tried to identify the ones that are safe and have low iodine levels. And so patients who are less inclined to cooking from scratch could go there and find a list of things they confined in the supermarket that are low Ida compliant, and then you want to raise the patient's TSH on day. Traditionally, we did that by making the patient hypo thyroid because we had no other choice. It's really miserable. We now do have her trope in Alfa, which is synthetic TSH. There's very little reason to do Hypo Thyroid Preparation and patients now just because, really, the toxicity is much more than we appreciate it. When we had no other choice is occasionally we'll do it a patient, just really. Some patients just don't want to get any other medications. Other times, sometimes we see a patient, and for whatever reason, they didn't take their post op thyroid hormone replacement. And they're already Hypo Thyroid will treat them. But otherwise, for your patients sake, just typically treat them with common in TSH. Next slide, please. As faras radiation safety precautions. The patients will need to follow these after treatment, and it's a lot easier on the covert era. We basically just tell patients to practice social distancing from their family as well as from the public, so as long as they're 6 ft apart from people. No one gets significant radiation exposure. Um, the levels. The specific requirements are set by the Nuclear Regulatory Commission, but different states, And even in some places, municipalities like New York City can interpret those on their own. And so the interpretation may vary by sight and by state, so follow whatever your local ones are. The one thing I cautioned people is that the guidelines are already very conservative. And when they've monitored members of the public patients, family members, um, they found really that there's very little radiation exposure, anyone well below the regulatory limits. And so they're already conservative guidelines. So we see guideline creeps. Sometimes when people say, Oh, I'm gonna add a little margin of safety and then the next person adds a little margin. All of a sudden we're doing things that are way more than we need to. Next slide ast faras dose. Consul ec Shin. I'd love saying, you know, if all you have is a hammer, you see every problem is a nail. As the regulatory requirements changed over the years and were permitted to give higher and higher doses is outpatient, Suddenly we needed to give higher and higher doses. Over the last 10 years or so, a lot of the research has been on finding the lowest effective dose. And many, many studies have shown that in the oblate of setting 30 militaries, is Justus effective as any dose higher than it at much lower Texas City? And so, in all those patients where your goal is, Teoh a blade residual thyroid patient doesn't have any of those high risk features, even if they have positive lymph nodes. That alone doesn't necessarily qualify. 30 militaries is generally sufficient and perfectly effective. A es from that are very rare. We worry a lot about secondary cancers, and there was this paper in 2018 and J. C Oh, that was a, I think, a very flawed analysis that looked at risk of malignancies after treatment. Eso There certainly is some risk, and we want to treat patients who need therapy, not those who don't so avoiding therapy and the ones who really don't need it and then earning on the side of that 30 military dose in most patients unless you really have a clear reason to give judgment therapy positive surgical margin, extra nodal extension, things like that. And then, as faras imaging is concerned, we can image. I am an image or I love imaging. It pains me to say this, but in many cases, the image ing isn't helpful. So post therapy scans are very useful If you give a patient dose of radioactive iodine therapeutically for thyroid cancer imaging, post therapy is certainly helpful. The pre therapy scan is debatable. I think it's reasonable to do it. It's reasonable to not. So if in your center it's not typically done, that's okay if it's typically done, I think that's okay. Surveillance imaging. So that scan a year or two years or three years after treatment is almost always useless As much as I love the volume, and I'm sure our business administrator would be cringing if you were on the call. Um, generally, there's almost no reason to order these scans. So so think twice, three times before ordering one. And then the one other thing that I think is something that comes up often assists have. They're filled with fluid, and that fluid is in slow communication, so cysts don't exactly concentrate the radioactive iodine. But the iodine slowly washes in and slowly washes out so often at the time of post therapy scan, you can see radioactive iodine within the cyst, and it looks like a hot spot. So here on the images, you see a benign time exist. Um, that you can see on spec. C. T. Is Clearly it looks troubling, but it's not. You can see him in premenopausal women very often in ovarian cysts, um, renal cysts, things like that. So in that case, image ing with something like Specks ET can be helpful to exclude him a test assist. But be aware if it's a really low risk patient, it's probably just a cyst. All right, thanks again. Um, so, based on the features of this case, including all of the positive notes the patient did, in fact received when I won 31 therapy. So Susan, Now, for this case, what would follow the How do you individualize followed care for your patients? Sorry, Muted first time. So it's all about individualization. So, as Dan mentioned, this patient with lymph nodes that are less than three centimeters is probably mostly an intermediate risk of recurrence patient, even though the stage one, which would mean that the risk of recurrence could be 25%. But that is not necessarily the risk of recurrence as we follow our patient through her journey with thyroid cancer and here because the patient has had thyroid ectomy and has had radio wide on. We can use cyber globulin, sort of RPS a the protein on Lee made by normal thyroid and by thyroid cancer to follow our patients. So what we do is we take our patient who may have had an initial intermediate risk of recurrence on what we do is we do something called dynamic risk stratification, where we modify that initial risk based upon the patient's outcome, using the two most important pieces of data that we can. The serum thyroid globulin on the neck ultrasound. So after surgery and radioactive iodine generally within the first 6 to 12 months, we get a TSH and the thyroid global TSH, obviously, um, to make sure our patient is appropriately treated with thyroid hormone, but a thyroid globulin and neck ultrasound on what we can do with those results is we can put our patient into four different categories of response. So when the excellent response to therapy, everything looks great. The thyroid globulin is very, very low, and the ultrasound is fine. We can have a biochemical and complete response where you could detect the thyroid globulin generally over one, but the imaging is negative. Ah, structural and complete response, where the ultrasound or maybe even a chest CT, Because the thyroid Libyan is very high to text distant metastases and then not everybody falls nicely into the three categories. So there is something called an indeterminant response, which is acceptable where the thyroid globulin is detectable at a low level. And there may be some small thyroid bed nah, jewels that you see that are do not have suspicious imaging features. So putting patients into these four categories each of them is associated with different risks of recurrences. And I'll remove the structural and complete because here you have defined residual or recurrent disease already, and so what you can then do is take that patient who may have had that intermediate risk of recurrence after surgery. And if that patient now falls into the excellent response to therapy, TSH could be normal. Thyroid globulin has checked annually on if the ultrasound was fine, since there is still a low risk of recurrence the median time for recurrences about 3 to 5 years. So the ultrasound doesn't have to be annual, however, Um, if the patient falls and the indeterminant category, where the thyroid globulin is detectable, sort of over one, you might be a little bit more concerned about Sorry, the thyroid gland that is detectable but is between 10.2 and one. You might be a little bit more concerned. Not quite as concerned is when we get to the biochemical incomplete, the TSH could be in the normal range. You check the thyroid globulin annually, and you follow the ultrasound based upon what you see. So if something is stable after a year, you might increase the frequency of ultrasound. But if your thyroid globulin goes from 0.3 to 1.5, you have to image. So these patients with thyroid globulin is that air just a little bit higher 0.2 to 1. You might follow a little bit more carefully because they have a 15% chance of her currents and those that air called biochemical incomplete because their thyroid globulin is over one, um, but provided their ultrasound does not show structural disease. We keep their TSH a little bit lower. We follow them more carefully. Looking at whether there was a change in thyroid globulin on the frequency of thyroid globulin may depend upon the trend. Is that remaining stable at 1.5? Or is it going from 1.5 to 2.5? And we have to begin to image? However, it turns out that patients with detectable thyroid globulin about 30% of them will have a decline in thyroid globulin over time. And so maybe you could go from a biochemical incomplete to an indeterminant or even an excellent response to therapy. So, based upon that thyroid globulin, an ultrasound that you do 6 to 12 months after the initial therapy with surgery and radio iodine, you could begin to then have that conversation with your patient. Although your initial risk of recurrence based on your pathology was 25 to 30% you now have an excellent response to therapy on the likelihood that your thyroid cancer returns is less than 5% and I think probably over the next several years you're going to be seeing how an endocrinology will work with our primary care colleagues to have many of these patients return to primary care for annual TSH and cyber globulin monitoring. Similarly, for those patients after low back to me. All right, Susan, thank you very much. Um, we got just a couple minutes. Many, um and I see, uh, you know, just with all of our questions through the Q and a chance have been answered by our Panelists, e accidentally marked. A question is done. When I meant to type E, I answered. Somebody asked about our Someone has had surgery and radio iodine. And there's a calcified neck limp note that it's seen on the biopsy is negative, um, from the lymph node. Can you remove it or observe it? So, unfortunately, there's some really good evidence based guidance here that if lymph nodes in the lateral neck or the central neck, even if they are positive for thyroid cancer provided it's very low volume disease that those can be followed Sona graphically with surveillance with intervention if they grow terrific. That student, could you speak briefly about third level and antibodies how those impacts are both. Yeah, so, um, thyroid globulin is the protein that's made by the normal thyroid and thyroid cancer. And, um, it's not quite as simple as I needed seem, um, in some of my slides. But about 15% of our patients with thyroid cancer will make an antibody to thyroid globulin. That makes it very challenging to measure the thyroid globulin. So in that case, they're very good data that you follow the cyber globulin antibody level. And, um, there are ways to categorize patients into that excellent, um, and thean determinant and even the biochemical response to therapy based upon the trump fiber globulin antibodies. So if they go away, they could be an excellent response. If they remain stable or decline, they can have that indeterminant response. That is really quite good. And if the antibodies increase, that is considered a biochemical, incomplete response, and you have to look for metastatic disease. Terrific. Um, well, I think that brings us, uh, just about ready to eight o'clock. So And in that time, he was gonna do have time for one question. I think that's Ah, you're right. Well, I'd like to thank all my colleagues for helping make this presentation. Susan Heather drawing Dan for joining today. E thank the A C C staff for the organization and so everyone for making time to log on for this conference and for the big questions. And also just a plug Thio, please join us for our next webinar, which will be the management of high risk their cancer on April 21st. Thank you much. Mm. So we can go right by. Look. See you later. Thank you. Thank you very much.