Experts from Penn Medicine discuss approaches for radioactive iodine therapy in aggressive thyroid cancer, clinical scenarios where external beam radiation may be indicated, surveillance strategies for high-risk patients and indications for intervention. Panelists include specialists from medical oncology, surgery, radiation oncology and nuclear medicine.
@PennMDForum Management of Low Risk Thyroid Cancer Management of Thyroid Nodules Penn Medicine Thyroid Cancer Nodule Management and Covid-19 Penn Medicine
Okay good morning everyone and um thank you for joining us very early on this morning, a little bit late, there was some technical issues um but we're so pleased that you could all join us this morning. Um Let me start by um sharing my screen. Um Here we go and welcome to the CNN approved webinar sponsored by the endocrine disease team here at the Abramson Cancer Center at Penn Medicine. Um Our goal today is to focus on the evaluation and management of patients with high risk thyroid cancer, follicular cell origin, so not medullary cancer today um that will be for a future webinar. My name is Susan Mandel and I'm pleased to join you. I'm the chief of endocrine here at the Perlman School of Medicine And I'm joined by four outstanding colleagues and friends who's disciplines truly represent the multidisciplinary collaboration essential for the care of this very challenging patient population. First from head and neck surgery. Doctor are italian from nuclear medicine, dr dan prima, from radiation oncology, Dr SAm Swisher McClure and from medical oncology. Dr Marcia breaux's. Um Today our goal is to define and review the approach to a patient found to have high risk thyroid cancer which is both evidence based and patient centred. And we will focus on initial therapy, appropriate surveillance and additional treatment options is indicated as the course of the disease progresses over time. Since our webinar will discuss and highlights points of care relevant to the management of these patients across their care continent. Their care continuum will be sharing the clinical vignette and verbally providing the pathology results and the radiology results. Um This is our disclosure side here and our objectives so assessing the approaches for radioactive iodine and aggressive thyroid cancer, identifying clinical scenarios where external being radiation may be indicated reviewing surveillance strategies for high risk patients with thyroid cancer and indications for intervention and recognizing the very important role of systemic therapy in metastatic thyroid cancer. Um so again, so pictures here. A couple of these are a little bit older. Um and all of us have become a little bit older, but all of us have as much energy as we've always had and I am really thrilled to welcome all of our panelists today. So um you'll see people's pictures as as they are directed as questions are directed to them. But we'll start with a case. Um The webinar is live and will be conducted as a panel discussion. So at any time during the webinar please submit questions using the chat box sent to all and we have reserved time at the end for questions. Um um to answer the session is being recorded. There will be a link. And for those of you who submitted questions in advance we've tried to incorporate the answer is dispersed through the webinar. So here we have a 47 year old male who felt a lump in his neck while shaving. He has no risk factors for thyroid cancer, either personal risk factors or a family history. And on his ultrasound he had a left mid 2.7 centimetre thyroid nodule that had all of the high suspicion features that we look for. A tyrant's five nodule. It was hippo Kotick solid with irregular margins and punkt eight academic fosse. And also an ultrasound appeared to have extra thyroid, all extension, both anti really and posterior lee. Um The lump that he felt was actually a left lateral cervical lymph node. That was about three centimeters. That's what caught his attention while shaving. And there were multiple abnormal lateral neck lymph nodes. He underwent F. N. A. Of both the nodule and one of the left lateral neck lymph nodes. And this was papillary um carcinoma. So our uh patient is now referred to you. And can you walk us through how you plan surgery for this patient? Is there a role for cross sectional imaging your inter operative strategy? Um And um you know what you might anticipate finding? Thank you Susan and welcome to all. Good morning. The patient's ultrasound gives us a lot of information. I would add cross sectional imaging a ct scan and contrast is reasonable. The contrast is going to be uh washed out over the period of time that the post op period includes prior to the patient getting radioactive iodine. So I think that's something that's relatively more accepted and something that many of us actually would have avoided 10, 15 years ago. We would look at that that imaging specifically to look at the high extremes of the neck, the retro fire in jail, the periphery, in jail nodes and also to look at disease that may extend below the clavicle, especially in the central compartment but also laterally as sometimes can be identified. The ultrasound is going to be our guide. A lot of this is counseling our patients are worried about the aesthetics of their operations. So when I frequently we'll use a cartoon all cartoon out that we're going to dissect out the compartment of nodes. Level two through four including parts of level five, the transfer cervical lymph nodes. I wouldn't necessarily skeletonized the spinal accessory nerve in the posterior triangle, but we would oftentimes see it securely and to put the patients at ease. Central compartment, recurrent laryngeal nerve monitoring via the endotracheal tube and trapezius, monitoring for spinal accessory um function are really things that give the patient a lot of peace of mind. And actually as a surgeon that gives you a good guy to understand you're doing things in a way that's optimally safe. The extent of the incision each of us are going to do slightly differently. We have a great team of surgeons and endocrine general surgery trained, had neck trained. We all use fairly small incisions and we all do this compartmentalize dissection. I think one of the questions that the patients will ask, where maybe we're going to ask ourselves is what do you do with the central compartment? And the central compartment is really critical to consider, especially when there's lateral neck lymph nodes. So almost all of those patients and the papers range uh and and percentages. But I quote a paper that says about 85 of people will have central compartment disease if they have lateral compartment disease. So I will address the central compartment on the gypsy lateral side. I will definitely look at the contra lateral side. Of course our goal is preservation of the parathyroid as well as the recurrent nerve. So I think um Susan that covers the general points. You were wanting to cover a lot of our patients also want to know about function after work after the surgery. So they're most common. Side effects are going to be some stiffness, potentially range of motion issues. So we will definitely we've in physical therapy to help them recover in the most expeditious way. Thank you. Thank you. Um I figured you'd be good to um get everybody some faces here. So let me just see. I think I can get this. Oh it's not quite working as I wanted it to but let's see. Um Okay so we'll go back to here. Let's get some places there. Okay so pathology, so not surprisingly this is a high risk pathology. It is a 2.7 centimetre. Popular carcinoma. Call sal variant with vascular invasion, extra thyroid, all extension, both to the strap muscles. Interior lee as well as to the parathyroid, all top soft tissue Um positive margins um and uh the lymph node dissection on level six. There were some positive lymph nodes and these were not microscopic. Um a task to see is the largest metastatic lymph node was one cm and the lateral um Neck. Um the largest lymph nodes sorry was three cm 3 m with extra nodal extension. So I'm really quite extensive disease and something that the american thyroid association would consider high risk recurrence um from the Uh from the 2015 guidelines. And I'm sorry there is a type of here as well. It was 13 out of 19 lymph nodes were positive in the lateral neck sam. Something that comes up a lot is um you know patients have heard this larry cancer is a head and neck cancer and they know about radiation for other head and neck cancers. Can you comment here just on when do you consider external beam radiation and a patient after primary surgery for papillary carcinoma? And then we'll obviously calling you later as our patient progresses. Sure. Good morning. Thank you Susan. So um you know I think the first point to be made in these cases in general is that most patients with differentiated thyroid cancer will not require external beam radiation therapy. Which is certainly in contrast to patients with other head and neck cancers, notably squamous cell carcinomas. Um and so you know in this patient, despite the aggressive and high risk disease, we you know at pan at least would generally not recommend postoperative external beam radiation therapy. The patients for whom we would more strongly consider. External beam radiation therapy would be those who have localized or regional disease in the neck that um that is grossly under a selectable. So gross residual disease after surgery. Um that is non medical to a a gross total resection those patients, we would consider a delivery of external beam radiation therapy. Um even patients where they have positive surgical margins after after surgery, if it's a microscopically positive margin. Uh National guidelines um indicate that external beam treatment can be considered in that situation. But I think it has to be weighed against the option of close observation or surveillance in that situation. And there's not been a randomized trial uh to kind of help further guide treatment in that decision. But given the toxicities and both acute and long term side effects of external beam radiation therapy in this area the body. Uh at penn at least we would generally um favorite close observation in those patients Certainly in this case specifically the patients under 50 years of age. And that's also a you know, as we're all aware of young age is a favorable prognostic factor. Um SAM I just like to follow up you've gotten a couple of questions in the past about poorly differentiated carcinoma as opposed to tall sails. So if this were a poorly differentiated carcinoma with the exact same pathology features vascular invasion, the same thing. Just sort of microscopic residual tissue and a younger person with that change your approach to external beamer. We can still do this close watch and And wait. And then by the way, Dan, I'm going to ask you the same question of poorly differentiated carcinoma would change your radio iodine dosage. But start with Sam 1st. Sure. So poorly differentiated carcinomas may be less likely to respond to radioactive iodine. And so the overall risk of recurrence may be higher. Um The uh you know I I don't know that it would change my decision making in this specific patient given the young age. Um You know if I think that if there was an early recurrence um you know in the immediate postoperative period if there was a disease that was already invading visceral organs at the time of presentation or threatening you know vital organs in the neck, the larynx trachea, the esophagus at the time of presentation. And those are the factors that would really drive me to recommend external beam radiation therapy immediately. Great, thank you very much. Um Let me go back to my crazy screen share again with this um where I seem to keep going back to our but we'll come over here um And uh so I'll leave this in the non presentation mode just so that you can see it. So no external being here for this patient whether it's tall, sell or poorly differentiated. However, something that I do think is important here um and this would hold whether it's poorly differentiated, whether it's classic, whether it's turtle cell, whether it's tall cell is as an endocrinologist. When I see these patients post operatively when vascular invasion is present, we generally order a non contrast C. T. And so that was done here. And this patient had about 22-3 mm. Solid lung modules bilaterally both by Bassler and in the upper lobes. So something that in somebody with no other risk factors for some type of um small modular pulmonary disease or interstitial lung disease would be really quite suspicious for papillary or for thyroid carcinoma metastases. And you can see that post operatively only both Iraq's and his TSH was 0.3 thyroid globulin was 4.5 and his antibodies were negative. Um So dan um why don't you talk us through? Um I went 31 planning administration and I have your slides here. And if you could include how any of this report, we differentiated how it would change your management. And there is a question in the chat about somebody who got 250 million curies. So if you could sort of talk about your dosage planning as well um in a patient and you know how you select the appropriate activity that you administer. Sure, thank you. Good morning everyone. So I think radio iodine is an interesting topic. Next slide please. So there are three kind of situations where we want to give radioactive iodine. The first is ablation where we're just trying to get rid of whatever normal thyroid is left behind by even the most thorough surgery. Um We want to make the thyroid gland and undetectable improve monitoring in the future. And that's a dose are a treatment where we have very strong evidence that low dose of 30 militaries has a very high success rate equivalent to higher doses. And so in those cases that's typically what we're gonna do. Adjuvant therapy is a little more controversial. The data is not very strong, but a lot of that is because the data was gathered at a time when we didn't do strong data gathering trials and it's become standard of care. So would be virtually impossible to go back and do randomized trials. But it makes sense that a german therapy works and most solid cancers where it's been tested and it should work here. And so we think about typically a higher dose with that. But usually a pen, we've really standard on standardized on 100 militaries for an adjuvant therapy, unclear what the optimal doses. But at that dose we have what we think is a fairly favorable risk benefit ratio. And there's not strong data that a higher dose would do better than that. And then there's the third category of therapy where you have a patient with known advanced or metastatic disease where we're trying to treat the disease we know about. Um and in that case typically we're thinking about a maximum tolerated dose and we may need to do does symmetry in order to determine that dose next slide. And in this case I think we have a hybrid dose. And there's this fancy word called Theranos sticks which is near and dear to anyone in nuclear medicine because it's really the essence of what we've been doing for over 80 years is we give a therapeutic drug that we can also image. And from that image we can tell whether or not the therapeutic is hitting its target. So you have this therapeutic and diagnostic component all in one And diagnostic those low dose I want 23 or low dose. I won 31 diagnostic scans have pretty low sensitivity. So because you're giving a low dose, your imaging a day or two later um you're not clearing from background tissues as well. The contrast is not really great. Whereas post therapy scans are very good. You're giving a much higher dose. You're waiting about a week for them for the iodine to clear out from the normal tissues. If you do not have a positive post therapy scan, it's very unlikely the patient will benefit from radio iodine. And I know nuclear medicine is often unclear medicine and we're looking for that blur within a bigger blur with radioactive iodine therapy and thyroid cancer. It's not like that. If you can't see it, if you have to squint and convince yourself that something is there, it's probably not enough to really give a therapeutic benefit to the patient. And so if it's not clearly a positive scan, it is really important. And there is this dichotomy that radio iodine remains the most effective therapy for metastatic thyroid cancer. It's super effective in the patients that take it up and we see some patients and I'll show you an example later. But the flip side to that is it's entirely ineffective and Aydin refractory patients. So I love the expression that if all you have is a hammer, you see every problem is a nail. And for a long time the only hammer we had in thyroid cancer was radioactive iodine. And so patients who didn't respond to radioactive iodine, our only option was more radioactive iodine. And so that's what we tried. Thanks to people like dr brose who has led a ton of work. We now have not one but multiple drugs approved for Aydin refractory thyroid cancer. And so I think the most important takeaway is that once you've determined that a patient's Aydin refractory, make sure that they get access to those drugs that work in Aydin Refractory disease. There was a question about genetics and it is interesting, there are some emerging data that suggests that some of the drug, herbal mutations that you might see on a genetic panel in advanced cancer can predict ride in refractory disease. A lot of the work has centered around the raft and TERT mutations. A patient with either of those has a fairly high likelihood of Aydin refractory disease. A patient with both of those mutations, so be ralf and TERT is almost certain to have aydin refractory disease. And so we typically would not do a lot of therapy in those patients really quickly when we do the radioactive iodine administration, we want to deplete the body of iodine. We want to raise TSH virtually always with recombinant human TSH now fire atropine alpha very safe to use. Even in advanced disease. We do want to screen the patients who are at high risk for brain metastases. So those who have known vascular invasion and evidence of metastatic disease elsewhere, We typically do do a diagnostic scan and in some cases it can help if we're on the fence in a case like this. If we did the diagnostic scan and there's clearly a lot of uptake in the lungs. We would switch that patient and judo symmetry at that point and give a maximum dose Most of the time. We don't see that will give them that a given dose. 100 militaries get the post therapy scan and definitively know whether or not more radioactive iodine is likely to be helpful in this patient. Next slide the law abidin diet. We try not to reinvent the wheel. There are two excellent organizations. One is like a dot org which has a whole cookbook, basically cooking things from scratch to make them low. Aydin lid life community dot org has a different approach where they found prepared foods that they've confirmed to be low iodine. Um we don't want to torture people. So they're on the diet for a week prior to therapy and then the second day after therapy. So if they're treated on a Wednesday, friday morning, they can wake up and eat whatever they want next slide. Um And I did mention this on the prior slide. So thyroid hormone withdrawal is really unpleasant when we didn't have an option. We got patients through it, but we have an option and so very rarely do we do thyroid hormone withdrawal. Um There's really no evidence that patients do worse with. Um We're comin to human TSH and it's usually the better option with the caveat that patients with brain metastases. You want to be careful because you can get swallowing next slide. Um And I mentioned, oh symmetry is useful if we're gonna want to treat with the maximum tolerated dose in a patient with known aydin avid metastatic disease. So this is really not important to do if you're if a patient is I don refractory, they're going to be, I don refractory whether you give 100 militaries or 400 and so you do want to have some strong rationale to believe that the patient is aydin avid before putting them through this next life. And just to leave you with that, these are two separate patients on the left is a patient who had widespread Aydin avid disease. You can see the first post therapy scan with a lot of remnant in the neck and bilateral lung metastases. A year later was the neck disease was completely a bladed, needed another dose of radioactive iodine for the lung metastases. This is a patient I treated way back in the dark ages of residency and I recently found that he was quote unquote lost to follow up when he and his wife moved down to the Carolinas to have a happy retirement. No evidence of disease. On the right, on the other hand, is a patient who ct looked virtually identical to the other patient and had neck disease. Diffuse lung metastases. You can tell this is a post therapy scan where there's really no significant retention. You can tell just because there's really no retention in the body. You can't even tell the edges of the body. That's just noise of the background. And this is a patient who's not retaining Aydin and is not going to benefit from radioactive iodine, but can benefit from those other therapies that are available. That DR Bruce will talk about momentarily. Thanks. Thank you, dan. Um so, coming back to our patient then, um, unfortunately, our patients can look like the right one. Although there was there was some uptake in the neck. So but no uptake in the lungs. So this would be somebody that we would consider iodine non added in the lungs provided these are lung mets, which is a high likelihood and reminding you of where his post operative TSH is. So Marsha, can you join us to comment on the relevant oncologist at that time? And also there a psychologist at this stage. But also there are a couple of questions about solid tumors sequencing and I know you're going to be speaking to us later and it's very important and systemic therapy. But when you consider it's important to do solid tumor sequencing, is this the time or would it potentially be later? Sure. Thank you, Susan. So basically my approach is that I'd like to see a patient as soon as our ai refractory disease has been documented and the reason for that is we don't know how these modules are going to behave many times in retrospect. We can see that they behave well but we don't know that the get go. So in my opinion they need to be seen at least once by a thyroid cancer oncologist. Who knows both. Obviously oncology but also no thyroid cancer. Um The second thing is about this patient is that there's a lot of education that needs to go in it. So if these are ei refractory disease modules takeoff they'll need to actually have a little bit of education. Um but like Sam I would um I would also recommend um surveillance at this point because we want to we want to be treating disease that's one a certain size and we also want to treat disease that's actually growing. Um the actual decision about when to start is actually related to multiple factors, including how fastest growing the locations are. Some very high risk locations that even if they're small burden of disease, I would start earlier. Um and so there's a lot of things that go into that treatment planning. Um But much to say that I I think the main thing is that they should at least meet the oncologist and the oncologist should partner with the endocrinologist to do um the surveillance going forward so that there can be preparation for when the systemic therapy would be needed. Um As far as genetics go, I prefer to do the genetics myself because that can also be determined a little bit by the course of the disease. If the patient has no disease for a while, I wouldn't do genetics for a bit and then I might choose to do the genetics on an advancing nodule. These panels tend to be very expensive, suggest doing the genetics now on the primary may not be as useful if later on they have a rapidly evolving nodule. I'll be wanting to get the genetics on that instead. So usually I would hold off on the genetics um Unless and sometimes it's been already done because maybe dan has needed to know what the the Wrath and TERT status was and maybe they got that from the genetics that was done on the thyroid nodule is initially. Um But I would not be ordering genetics until I'm getting closer to just starting the patient on systemic therapy. Thank you. Thank you. I'm going to um come back to a slide for a second. There was a question about what we meant by the lateral and the central neck and um courtesy of Rachel tells who quickly sent this. Um Are you could you just take us through um what is considered the central net compartment and the lateral neck compartment? Um In the gladly. That's a great question Rachel, thank you for the slides. The level six which is that anterior right over the Larynx. Thank you. Susan is defined anatomically from the highway to this below the manubrium. From character to character. uh more commonly for the recurrences were going to be seeing level six and 7 disease that alone the level of the thyroid cartilage and below. And it's going to be defined by your radiologist and ultra and endocrine team on their surveillance and the guidelines are going to guide our behavior on this area. But that's that's the central compartment. So during a standard thyroidectomy we're all getting to evaluate the central compartment by visualization help patients. And if you use in tropic of ultrasound. It's it's there for us to evaluate the lateral neck is lateral to the carotid artery and jugular vein. It's the compartment under the sternal Clyde. Um asteroid it uh goes from level two which is the high neck down to level four which is the lower neck and level five is the portion of the neck that's posterior to the sternal Clyde. Um asteroid muscle. Uh The history of next surgery is fascinating. That's where the word radical neck dissection comes from. And our patients come in armed with this image of their next surgery. So a lot of what our endocrine colleagues are, even medical oncology discussions. I'm sure Marcia gets this question but we're really doing surgery to preserve all the key structures and remove the lymph nodes and fat that are surrounding the target area. It's a good question. Thank you. Thank you. Well that's actually going to be very relevant for our patients. So um he's seen by his endocrinologist three months after Radio I don. And his follow up chest ct fortunately shows not surprisingly in these cases that his lung modules are stable. His thyroid globulin is still approximately three and he has his first surveillance ultrasound. And um here he has a left level for lymph node That has the Sana graphic features that are suspicious. It's small at seven x 8 x nine but a type of co it um it is vascular and there's some punk state academic both side which you can see so suspicious for papillary thyroid cancer. And so of course we're all in this situation where although as endocrinologists we've had the discussion with our patients. But this is high risk for recurrence, which means approximately 30-35 chance of structural recurrence. This is something that we explain to a patient might be considered residual disease. It's very small. Unfortunately, the guidelines have said that Small lymph nodes, especially in the lateral neck where the smallest dimension is less than 10 and this is less than This is seven can be followed. Um so our uh um when you see these patients and we see them together, um your approach to these people and um how you talk to them and um is this the right time for re operation? So Susan I think you hit the nail. You hit the target. Really? It's a conversation and not an operation for most of these folks. The guidelines guide us to wait till the lymph node is larger than a centimeter. And the caveat to that is now you're dealing. And the patient really has this concern. My cancer is back or is my cancer active? And the surveillance story tells a lot of what's really going on. So unless that lymph node looks like it's going to invade the Vegas by some of the imaging criteria where there's something unusual clinically about it. Most of these lymph nodes, we're going to watch until they become a senate member or larger If it was the central compartment and it was larger than eight. Then the guidelines say to consider surgery at that point. But I have to tell you, the conversation may seem more intense than some of the conversations to take somebody into surgery or other treatment. And it's because it's a it's an emotional intellectual disconnect from treat my cancer versus watch it. But the journey together with your underground colleagues really helps kind of take the patient to where they want to be. Um and sometimes I'll check. Those patients would follow up exams even though I can't really feel much Susan back to you. Thanks. Thank you. Okay. I still keep ending up on that one and one day. I'll figure this out. Okay, so um um here is our patient now. So he um we have a conversation, the surgeon, the endocrinologist, the patient of a conversation, and we follow the small lymph node for three years and it remains stable, which is pretty common for many of these lymph nodes. But his lung modules, which are likely intellect metastases at this time, Have slowly grown over three years from about 2-3 mm to about four. And the cyber globulin has increased from 3 to 12. And I think the challenge for entrepreneurs ologists always is how much of that increase in thyroid globulin is attributable to the slow growth in the volume of his lung metastases or is something else going on? And we have to temper that with the fact that we know that this is tall sell or even if this is poorly differentiated, there may be still some thyroid globulin secretion, but it's not very effective secretion. So if this were a classic papillary and lung metastases, the thyroid globulin might be in the hundreds, but we have to take any change in the thyroid globulin um with serious consideration for things like tall cellar or even poorly differentiated, which can make some thyroid globulin. So my concern is an endocrinologist is is all of this increase in thyroid globulin attributable to the slow growth in his lungs or something else going on. And um he did have vascular invasion and my concern always with my patients as patient has a great quality of life. So is there something else that I need to know about that might potentially adversely affect? Is like so dan. Um in this situation can you talk us through some of the additional imaging that might be helpful here in a patient with 12 seller, we could even make it poorly differentiated. Direct counsel. Sure for sure. So I think as the as the thyroid gland thyroid globulin rises we can think about F. D. G. Pet ct. Or in the situation of poorly differentiated cancers that may not be making thyroid globulin. You can think sooner about F. D. G. Pet ct but it can give you a couple of pieces of information. One in the item refractory disease setting. It is quite sensitive. Um But in the iodine avid setting it actually or even in the indian refractory setting it has prognostic value. So in a patient with known progressive advanced thyroid cancer, so the lung nodules are very likely thyroid cancer at this point they're growing slowly. They have the distribution. We can be pretty certain. I saw a question about whether or not you had bronc the patient. I think there are some situations where we want to get tissue. I think this one it's everything is so definitive that probably there's not much benefit to confirming that it is because we know. Um But a negative F. D. G. Pet in that situation doesn't mean it's not thyroid cancer but it means that the patient is likely to have a still a fairly indolent course and and sitting pat can be very reasonable and you can also have sensitivity for detecting other sites of disease. So in this example you can see on the F. D. G. Pet ct, the lung nodules were negative. So even though the thyroid cancer they're not F. D. G. Avid, there's still relatively indolent. But we see this lyric metastases in C. Seven. That is F. D. G. Yeah but it's not blazing hot but it's clearly positive. It aligns with politic lesion. Um And we can say with fairly good certainty that not only is this metastatic thyroid cancer but this is something that has a more aggressive genotype. Thank you. Um I think the comment that john made which is um a pearl for all of us to take care of these patients clinically is that patients come to us and they stationed I have a pet scan. In fact we're often asked that question. Unfortunately most thyroid cancer is metastases are very slowly growing so that the fact that the lung modules are not visualized on the pet scan is probably a combination obviously of their small size. But we've all seen four millimeter lung modules that can be effigy Abbott. So the lack of F. G. Ability and the lung nodule confirms what we already know which is over three years. These are very slowly growing. Um And so hopefully our patient will continue that course for a while but does show. And also by the way, the small lymph node in his neck, which is also not growing as F. G. Abbott. So it confirms, you know about the biology of the disease. From cross sectional imaging. There was a question in um in the chat about whether or not all allegiance need to pick up radioactive iodine and typically unfortunately a patient's cancer course is going to be determined or driven by the most aggressive disease. So the stuff that's indolent will stay indolent and the more aggressive stuff will presumably grow and spread. And so I think it really is important that if someone has iodine avid disease, so someone has 10 iodine avid lung metastases. But a bunch of giant non avid bone and node mets that are growing and growing into important structures treating those lung metastases might make us feel better. It certainly won't help the patient. Um so so you need to be cognizant of what's likely to drive morbidity and mortality in the patient and treat that. So I think you kind of um in part answered this question. So patient and I have a discussion. So we have this new um lyrics C7 met which is confirmed um obviously on cross sectional imaging in something that's F. D. G avid like this. Is there a role for repeat radioactive iodine should be using that hammer again. Or should we turn to one of our other colleagues? And this is I was I made a mental note to thank Sarah for his comment earlier. Who said, you know I probably think about some more imaging and then Susan you mentioned if there's vascular invasion getting the Ct. I think sometimes we end up in a quandary when there is metastatic disease that we didn't know about before. And we don't know if it's Aydin Abbott in this case because we got the chest ct. The lung nodules were there at baseline and we know we didn't treat them with the radioactive iodine. I think there's no need to do further radioactive iodine in this case. Had we not known that we might be confused? And so should we give it a try and it might delay things by a month or more? And so I think it's really helpful to have that information up front. And I would say as an endocrinologist where my colleagues Caroline kim and christian Cobolli and I all see patients who referred in from many areas regionally. It's very helpful if we know about the duration of those lung modules. So the point that was made earlier with this case is that if there is vascular invasion and the primary tumor getting that chest ct without contrast is very important because if we can date lung nodule is to being present at the time of the initial radio iodine therapy. And if the post therapy did not show up, take in the lungs 3 to 4 years later when the thyroid globulin is higher and we see them as a consultation from one of our colleagues in the entropy community and now we see eight millimeter lung modules. If we know that they were there at the time of the initial radio iodine therapy, then that patient is not a candidate for additional radio iodine. And we often refer those patients onto Marsha. Um SAM though, turn to you. So um can you talk a little bit now about the role of radiation therapy and this sort of al ago metastatic disease where we have some other areas that are relatively stable but a new metastases. Sure. Thanks Susan. So um for for this patient, given the relatively limited extent of metastatic disease overall um and the indolent behavior of the lung metastases but this uh new focal progression in the in the c spine. Uh I think local directed treatment to the spine is warranted. And so the way we would approach this patient um you know, we obtain an MRI of the spine to further delineate the extent of disease and assess whether anything like ford compression was present. Uh If there was pathologic fracture in the vertebral body and any spinal instability, we review the case with our neurosurgical colleagues, particularly if there was concern about spine stability. Where if there was poor compression to consider decompression with the lamb neck to me or other surgical interventions, but barring those, um you know, we could address this uh this lesion in the spine with a form of radiation therapy called steri attacked IQ body radiation therapy or S. P. R. T. And what that entails is a uh highly precise and high dose radiation treatment that's delivered to the spine over a period of 1-2 weeks. And that treatment would be expected to be associated with a very high probability of local tumor control in the range of 85 to 95% which is critical for patients with disease in the spine. Given the morbidity. Um that would be a consequence of progression in that area. Mile apathy and and and pain and things of that sort. So we would recommend and offer S. P. R. T. For this sort of patient. Great um and Marcia before I turn to you and go a little bit further with his course when he gets worse and um he will be seeing you. There's a question about ethanol or R. F. A. For small lymph nodes in the neck. And I think that goes back to what are said is um we know that many of these remain quite stable and perhaps if it's the only source of metastatic disease, it's something you might consider. This is a patient who likely has known pulmonary metastases unfortunately has stability in this one lymph node area. So I generally find by having that conversation with the patient and the surgeon having it as well that they're really quite comfortable with the stability on imaging and not going for an interventional technique. Um, if there is a singular solitary metastatic lymph node. Um and that is the only source of metastases that is detected and follow up. I think that that is a discussion with the patient about what the intervention should be if an intervention is considered because remembering that there still is a role for active surveillance for low volume neck disease. So those discussions about interventional nonsurgical techniques versus surgery versus active surveillance all depend upon the patient, the patient's general, of course, what else is going on? Besides that lymph node? Um, your how good your surgeon is, um how good you are being able to do the ethanol or the R. F. A. So again, we're very fortunate that the techniques of image guided ethanol ablation and R. F. A. R. Techniques that are now available to us in our choice. So there are choices to be had. But those are all discussions with the patient but really importantly in consideration with the context of disease. Um think we're sort of up to date on questions. Do you want to answer one question that dan Rosenbaum asked, dan. One of the things that we see as an endocrinologist is sometimes you do have a patient who has multiple little um lung metastases and one is growing dissing Chrisley And those are the ones that we will send, you know, have a bunch of lung nodule is 3-4 mm, relatively stable. One is eight, One is 10, it's 12, it's speculated and we send them to our interventional pulmonologist and we diagnose and adenocarcinoma in the setting of metastatic thyroid cancer so that there are times that we never want to consider everything as thyroid cancer. But if something doesn't make sense, that's when we might actually go for tissue. And over the years I've probably diagnosed about 10 primary lung carcinoma as well. I've been following thyroid cancer. Um So with this, let me go back now to our next one here. So our patient gets the S. P. R. T. Just great. And now finally in years like for it to seven his lymph node is growing. No other lymph nodes yet. Remember this is residual disease that slowly progressing but his long modules are progressing to there are now about 40 lung modules that range from six millimeters to 1.2 centimeters. And I'm going to turn over the rest of this discussion right now to Marcia. Um to talk about the really critical role of a medical oncologist with expertise in thyroid cancer and Marcia especially comment on and Marcia and I talked about this because we've worked together now for over 10 years is how the intervention, um, timing has changed and what your surveillance strategy is. How do you decide when you're going to start therapy and what is the additional information you need in your choice of the different options? So, um, let's um, show your face here. Thank you very much. Okay, so thank you Susan. Um so just a couple of things that I toggled. I also want to thank our a for putting in that CT scan early on. One of the things that I want to point out is that if we have a patient who has just neck disease and nothing else, I think being more aggressive with the neck disease makes sense. And but in the back side of that, one of the things, and I think this patient shows is that you could have been very aggressive with the neck and they would have probably still shown up with this lesion in the spine. And so that's really the biggest argument for surveillance because just treating something that's not bothering the patient and is barely growing is often not going to be the site that will be a problem. Um, and on the cT scans again, it all has to do with what they look like. You know, differentiated thyroid cancer is always well circumscribed with really nice shape, usually round, um, a rounded ish. Um, and it really has some nice borders to it. As soon as I see a speculated lesion, we have one of two possibilities either it's an adenocarcinoma or we might be having somebody who has actually anaplastic thyroid cancer now in a plastic thyroid cancer distance sites is becoming more common. I think we're finding it because some people are living longer with their differentiated disease and so we can't completely rule that out. So, um sort of both to Susan and are I really do believe in getting those scans early. That's super important. Hopefully, by the time I would see this patient, I would have already been talking to this patient and following along with their disease. I probably would not have treated again the local disease except that if hit it really started to pace faster than the lung disease. And I was watching the lung disease and I thought, wow, you know, we could probably get another year before there's enough lesions that are really to treat systemically. I also like handling these off back to Ara and we actually have done this on many of our cases where a person can get that one nodule if the one nodule in the neck is the one that's growing. We can get another two years by what I call coasting the patient by going ahead and taking the one active nodule out and sitting and waiting for the next, whatever it is to actually matter that that's going to grow up. So the first rule of surveillance is to sort of make sure that nothing bad happens quickly. If I don't know the patient very well, I'll get a couple of cat scans in a row. Um for diagnostic imaging, I prefer the diagnostic cat C A C. T. With contrast because we're assuming now that dan prima has decided that he's not going to do any more radioactive iodine. And so the benefit of contrast is that there are some places where the contrast really, really helps delineate the disease. On the pleural lining is one area, and that can happen even on the pleural surfaces, inside the inside the lung, on the um septa of the lobes. So by having that contrast that can really highlight those even small modules, How I decide on when to start has a lot to do with 15 years experience of following these patients. And it doesn't fall down to a number of a number of lesions or size or even the rate of growth. A lot of it also has to do with where these are. Um and so the goal is always to predate symptoms. That's the most important thing. Um in the guidelines of the islands are very, I mean, they're very non specific about treating this and they're even less specific now because they're already six years old. And now we have many, many more systemic therapies. So at this point it really has to do with being in with an oncologist who treats these a lot. Who knows how to do surveillance when they can we like to see um patients do. So I feel like I'm well I love drugs, you know, like that's my thing. Um My my my first goal and and and um my first responsibility of the patient is to protect their non system. That system like therapy period of life because once they start on these, they often will require them for the rest of their life. So I'm telling them go on cruises, you know, go to Greece, you know, do all the things that they wanted to do. Um And then what we do is when we do have to start their prepared because they know what's gonna entail. Um We will at that point if we haven't, when I'm starting to see that in the next six months I'm going to start systemic therapy. I usually will start to pick where I'm going to get the genetic analysis for. Um now that we have targeted therapies that are both for point mutations as well as for the infusions, I will have to make sure I get a very good panel and then it will actually pick up both. But in spite of the targeted therapies, like we may have things for B. Wrath and Rhett um track fusions. Um There are also things like grass that are prognostic and Turkey that are prognostic. So we'll want to get these full panels to actually decide. And then the last I guess in idea or point that I want to make is just because you're a point mutation does not mean that that is the correct therapy to use in the first setting. For instance the data on the rap inhibitors is good but it actually it pales in comparison to the vet Geoff when that Jeff receptor live at nib and one coming down the pike cabos antonym. So um you really want to have an oncologist who has experience with all of these different therapies so that they know how to sequence them. And also then the success of our patients will have a lot to do with how well they manage the side effects. So anybody who gives these therapies can obviously get rid of the side effects by dropping the dose. Unfortunately that's not good for the patient. And so often I become not just the patient's position but I also become the patient's coach Um and I'm really often in touch with them a lot by cell phone or texting um as they start these therapies because what side effects they may have for, you know, different therapies will be different for each patient and how they tolerate it. There are lots and lots of tricks that I've learned over 15 years of giving them both ones that we knew about, but also ones that our patients have brought to us. And so based on whatever issues patients might have with systemic therapy, we usually can make it tolerable. I've had patients who are on systemic therapy for 15 years, so it really is something that can be a long term process. But you really have to have an oncologist who's going to be dedicated to them, who knows, thyroid cancer and most importantly knows how to help them manage a very high level a function Many of these agents, even when they're used in other cancers. Um it's almost anticipated lots of times. They're they're they're used with other agents. Those patients um clinical functioning won't be as good. And I think the expectation for how well they're going to do as much lower. But in thyroid cancer patients you know we have these 50 year olds were going to live a long time. It's super, super important. I will say that I prefer if we can avoid the XRT to the neck. Um When we can I pre I prefer that especially if we know that they have metastatic disease. And the reason for that is we've had a couple of bad effects where the scar tissue can break down and we can end up with fistulas. Um And uh either to officials or Catania specialist. Um and that can be a complication that can be difficult to manage. So um we tend to wait as long as we can but we don't wait too long because one of the issues that also happens is there are as we pointed out, some side effects associated with these medications and when we give these we don't want to have them on top of the fact that they're already symptomatic. So they already feel down because they can't breathe or they're coughing all the time and they're not sleeping. And then give them the side effects of the medication on top of that. So you really want to have somebody who knows how to read these scans in time. An initiation to happen before they're going to get system on as late as possible. But also before they're going to be symptomatic. Um And remembering also that in addition to the side effects of the drug, the actual breakdown of the tissue can be overwhelming. Unfortunately had a patient recently who just passed away and they passed away because they had where they're now in hospice because they had such big burden of disease that when we started treating it, their body basically couldn't handle the cancer burden even as it was dying. So it is incredibly important to start earlier than that. Um And so we know a lot about the data about that. We do know that patients anything with a centimeter more, but it's not really useful because you know, one patient with one cent one centimeter lesion can be followed. But a patient with 51 centimeter lesions all over their lungs has quite a burden of disease. So there's not really a black and white and the size even or when to do it. And there isn't even necessarily progression because of course if somebody is a four or five centimeter disease, I don't want to find out how fast it's growing. I usually want to do something to try to get get it down. The last thing I'll say is a roll of an oncologist is at that point I feel like we are constantly working with our colleagues were not usually alone. I'm constantly we're working with Ara or sam or dan. Not so much dan at this point because the radioactive iodine refractory but maybe is with regards to F. D. G. Pet. But really working with XRT and um dr Chilean and try to figure out when I have a solo a lesion that is actually progressing. What is it that I want to be treating and can I get away again with a local therapy? So we're usually passing these people back and forth and back and forth and having a conversation many times. Do you think this is one you could do? You know, I know we've done it a couple of times, but maybe we could get another couple of years and in most cases when I've done that, that's actually been what's happened. So it really is still a team sport even once I've taken over a little bit more of the management of a patient, but we continue to work as a multidisciplinary team. Thank you Marcia. Um I think you you can definitely get how people come in and out of the team as the patients um course progresses. And actually one of the questions was how do you reassure patient who you with, whom you've already had the conversation that there is metastatic disease, but you're not going to do anything about it. And that is a very challenging conversation and I think it relies on your comfort in knowing that this is something that's slowly progressive, which obviously at the first chest ct you don't know, but you know, over time, you also know this from the pet scan. I think one of the things that I've noticed as a position taking care of patients from endocrinologists who have amazing expertise in the wide spectrum of endocrine disorders, which I no longer share. Um, but because I'm focused on thyroid cancer is, um, is the, uh, if you are uncertain, your patient is going to be uncertain. So having marshals expertise to say, you know, I've seen this before, we can follow you or if we treat them are says, I followed small lymph nodes, dan knows what it's like to follow. Either iodine every disease or I don't have a non disease and an entrepreneur ologists who sees a lot of patients with metastatic thyroid cancer and can say, you know, this is something that can remain very indolent for a long time and when it doesn't, um, Marcia used to call me, you're used to call yourself our insurance plan, but it's a lot more than that. It's part of, it's no longer insurance, it's part of the whole spectrum of care. Um, I think we have answered. Um, There's a question about a 20 year old, which I did not see. Um, I actually don't have any open questions here. I don't know if it's in the Q and A. It's a question about a 20 year old with a seven centimeter poorly differentiated cancer for folk, I a vascular invasion and no lymph node involvement. So I think we sort of answered that that would be someone provided. The surgery is pretty extensive. That would get a chest C. T. Non contrast at the time, right after the surgery or before the surgery. We get radio wide and we followed very carefully. Um um And then one final question to just a brief comment because we're running out of time obviously a little bit more about determining iodine refractory status. Yeah. And so that's something that if you have structural disease so clear disease that you can see anatomically and you do a therapeutic dose. So 30 militaries or higher. Um And you don't clearly see that uptake on a post therapy scan. Then I think you can determine that the patient is aydin refractory. If you see uptake on the post therapy scan there it gets a little more complicated because then you can have visible uptake but not enough uptake to get a good therapeutic benefit. But those patients where you do see clear uptake typically you're gonna want to give a maximum tolerated dose and see whether the thorough globulin significantly improves and plateaus for some period of time. So if you give a patient a dose symmetry in a maximal dose and their thyroid globulin just continues to rise through it. That's another criterion for aydin refractory disease. Um We have time, we have one or two more minutes um dan there was a question about our protocol for thyroid and preparation for radioactive iodine. So if you could just because I certainly have also seen it differently but about the timing of the competent human TSH injections and the dozing. So patients get 09 mg of common human TSH given intra muscularly on two consecutive days. And the really important thing is the therapeutic dose should go in approximately 24 hours after that second injection. The TSH levels dropped very very quickly after the after they peak. And so you really want to get them treated at the peak of the TSH. And so that's why it's really important that you figure everything out counts back from 24 hours after the second injection. So typically we give injection on day one injection on day 22 hours later we give a low dose of I 1 23 the next day we do a scan and we treat the patient most of the time. We have a really good idea of what treatment dose we're going to give. So we have pre ordered that and we have it there and as long as the scan doesn't have any surprises we can treat them right away and make it very streamlined. If we see something on the scan that makes us change the plan then we would um order a new dose but that's pretty rare. Um We are at the hour and um there's still a couple of good questions in the chat. Maybe we can try to get back to you about those. We'd like to thank, first of all, I want to thank the panelists for their um for all their engagement, for their planning were participating here and most importantly for their collegiality and their care of all of our patients here at Penn um also to the Abramson Cancer Center staff, especially this morning with our technical glitches you guys really came through. So thank you very very much and thank you to all of our um our audience and our attendees who took time to get up early in the morning and to log on and join us and made the conversation so rich by interjecting your questions so that we could even further explore the journeys of our patients with aggressive larry cancer. So I wish you all a very good day and a good week. Thank you very much. Do we just stay as they like well. So we have okay when Susan we can stay in debrief if you have time or we can do that later. Oh it's fine. I've got to drop the kids off at school. Thank you everybody. Thanks guys. Thanks Russia thanks. Yeah the kids I think we're good. Um You are still alive though. Yeah I'm just looking about the ones we couldn't answer. Um Yeah we can do it another time. Okay and I have record of those those questions so. Okay thank you. Okay.