Evaluation and Treatment of Papillary Thyroid Cancer Webcast October 28, 2008 Dina Elaraj, M.D. Introduction

Evaluation and Treatment of Papillary Thyroid Cancer Webcast October 28, 2008 Dina Elaraj, M.D. Please remember the opinions expressed on Patient Powe...
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Evaluation and Treatment of Papillary Thyroid Cancer Webcast October 28, 2008 Dina Elaraj, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of Northwestern Memorial Hospital, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Introduction Andrew Schorr: Hello and welcome to Patient Power. I'm Andrew Schorr, and every two weeks we connect with you another important medical topic and an expert from Northwestern Memorial Hospital. Today we are going to talk about thyroid cancer and the most common type, papillary thyroid cancer, and this hits close to home for those of us at Patient Power. You know, our senior producer, Jamie Machala, who produces all of our programs with Northwestern Memorial, she is 30 years old now, but when she was 20, this came up for you, Jamie. Tell us the story. Symptoms and Diagnosis Jamie: So I was in college at the time, and I remember being at the library studying, and I was on the computer looking for things, and I just felt my neck, and I noticed a lump on my neck. And I already had had an appointment with my primary care physician about two weeks later, so when I went in I mentioned it to her, and immediately she thought it was definitely something bigger. I thought it was just something minor at the time, but she sent me immediately for an ultrasound and to an ear, nose, and throat specialist. And from there I had an ultrasound and I had a fine needle biopsy, and everything came back inconclusive. So they decided it was just a thyroid nodule, and they were going to go in and remove half of my thyroid gland. And on the day of the surgery they ended up actually pulling half out and testing it, and they did discover that it was cancerous, so they went out and asked my parents if they could go ahead and remove my entire thyroid gland. And my father said yes, of course. And so about six weeks later after my surgery, I had radiation I-131 therapy, and I am still followed fairly closely, but everything is fine today, and I just take thyroid replacement hormones. Andrew Schorr: And we are glad you are with us, and that this has worked out as it has. And I know with thyroid cancer typically and with papillary thyroid cancer this is usually the way it is, but let's learn much more about it from an expert, and that's Dr. Dina Elaraj. Dr. Elaraj is an endocrine surgeon at Northwestern Memorial Hospital. She

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is an assistant professor in the section of endocrine surgery and the department of surgery at Northwestern University's Feinberg School of Medicine. Dr. Elaraj, thanks for joining us. Is Jamie's situation typical? Dr. Elaraj: Thank you for having me, Andrew. And yes, actually Jamie's situation is quite typical. I have had so many people come into my office saying either they found a thyroid module themselves or their doctor found it just on routine physical exam, or sometimes they tell me, oh, well, I was having a facial, and my esthetician was feeling my neck and found my thyroid nodule. And so that's typically how it always starts is just with a thyroid nodule that's completely asymptomatic, and they go for further evaluation. And exactly like Jamie had done the first thing that we recommend is just an ultrasound of the thyroid gland which doesn't hurt, doesn't have any radiation involved in it and can really characterize what is going on inside the thyroid gland, how many nodules are there, what do the nodules look like. Sometimes the appearance of the nodules on ultrasound raise the suspicion of thyroid cancer or make one more or less suspicious in terms of recommending a biopsy. And then if a nodule has any suspicious features on ultrasound or if it's bigger than one or one and a half centimeters we typically recommend a fine needle aspiration biopsy usually using an ultrasound so we can very carefully target that nodule. Radiation Treatment Andrew Schorr: Now, is this typical where you will usually have some sort of radiation afterwards? Dr. Elaraj: Well, that depends. So what Jamie was talking about was something called radioactive iodine, which is a pill that people take one time usually after thyroid surgery for papillary thyroid cancer. And that's actually a little bit of an area of controversy in terms of how much does it help. Most people will get radioactive iodine, and the purpose is to destroy any remaining thyroid cells that are left in the neck after surgery. And a lot of people say, well, how can there be any thyroid cells left in the neck after surgery. I mean, didn't you just take my entire thyroid gland out? Well, yes, but we can only take out what we can see, and are there some cells left? Well, sure. There are always a few cells left, and sometimes a surgeon will deliberately leave a teeny, tiny bit of thyroid tissue behind if it's very close to where the nerves that control the voice insert into the voice muscles. And so the radioactive iodine will kill those as well. And so for right now pretty much all except the most lowest risk patients, meaning those with small thyroid cancers less than centimeter, no lymph node metastases, no aggressive features of the thyroid cancer, just one spot of thyroid cancer, etc., will get this radioactive iodine.

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Andrew Schorr: Now, I want you to clarify something for us. A lot of women develop thyroid problems. Dr. Elaraj: Yes. Precursors to Thyroid Cancer Andrew Schorr: And they have fatigue, or either underactive or overactive thyroid. Is there any connection between that that affects so many and thyroid cancer? Dr. Elaraj: You know, no, not really. And in fact most people who have thyroid cancer have normal thyroid function. Now, there is an entity called Hashimoto's thyroiditis which is an infiltration of the thyroid gland with lymphocytes. These are immune cells. And it causes a little bit of an inflammatory reaction in the thyroid gland, and those people eventually develop an underactive thyroid gland. And studies that have looked at an association with Hashimoto's thyroiditis and papillary thyroid cancer have found an increased prevalence of this condition in patients with papillary thyroid cancer, but does that mean that one causes the other? Not sure. Nobody knows. Andrew Schorr: Now, Jamie was just 20, so tell us about the number of people diagnosed with thyroid cancer and what the ages typically are. Dr. Elaraj: Okay. So thyroid cancer is expected to have an incidence in the US in 2008 of about 37,000 cases. It's the sixth most common cancer in women, and it has a median age of diagnosis of 45 years, so Jamie is actually a little bit on the young side for someone to be diagnosed with thyroid cancer. But it is more common in women by a ratio of about three to one. And although people have been trying to figure out why is it more common in women, they have looked at hormonal associations, they have looked at chromosomal associations, haven't really been able to pin down why it is that thyroid cancer is more common in women. Andrew Schorr: Now, is there a family connection? Dr. Elaraj: That's an interesting question. So about three percent of papillary thyroid cancers are familial, meaning that there is an inherited predisposition to it. And we know some familial syndromes that are associated with papillary thyroid cancer and I will just name a few. One is called familial adenomatous polyposis, which is a condition where people develop a lot of polyps throughout their colon, and those polyps in

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the colon predispose to colon cancer. Well, in a very rare segment of people with that genetic mutation they can also develop thyroid cancer, but it's not very common. There are a couple of other rare syndromes that we also know are associated with papillary thyroid cancer. There is something called Cowden syndrome, which is something called the hamartoma syndrome where people get hamartomas. They are firm, little tumors throughout their body, and it's due to a specific genetic mutation. And then there are a couple of others. There is an entity called familial non-medullary thyroid cancer, or we call it FNMTC for short, which specifically refers to papillary thyroid cancer in two or three first-degree relatives and has an increased risk of people in that family developing papillary thyroid cancer anywhere from three to nine times. And that specific genetic defect hasn't been figured out yet, and lots of people are trying to figure it out. They basically collect blood samples and thyroid samples and lymph node samples from people who have thyroid cancer in these families and are trying to compare them all to try to figure out a genetic association, but so far we don't know what the gene is yet. Prognosis Andrew Schorr: Dr. Elaraj, I'm sure the number one question you ask, and I am sure Jamie asked her doctors was what's my prognosis? How do you determine that? Dr. Elaraj: So prognosis is divided up into two basic things. One is what is a person's risk of recurrence? Meaning what's the chance that it's going to come back after treatment? And the other is, is this going to impact how long I live? Those are basically the two questions that people are really interested in knowing the answer to. And I tell them that we can't really give them any information about either of those two things until after their operation, because the operation is going to allow us to stage them. What does staging mean? Well, staging is a way that those of us who take care of patients with cancer are able to give information regarding prognosis. And the staging system for thyroid cancer depends on four things. One is the patient's age, and this is actually unique to thyroid cancer because people who are younger than the age of 45 have the best prognosis and can only have stage I or stage II thyroid cancer, whereas people who are older than age 45 can have stage I, II, III, or IV, just like breast cancer or colon cancer or lung cancer. The staging depends on the size the tumor, how many tumors there are, whether or not that tumor has invaded past the thyroid gland, has actually gone outside of the capsule of the thyroid gland, whether or not it's invading some important structures in the neck, whether or not any lymph nodes are involved, where those lymph nodes are located, and

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whether or not there is any distant metastatic disease. And taking all of that information together we are able to give someone a stage and then give them a prognosis. Andrew Schorr: Jamie was diagnosed at a younger age. Does that mean she just by living longer would have more likelihood of a recurrence? So this whole recurrence idea, you mentioned about age, that's one of the factors. Where does that come in? And how closely does she need to be followed? Dr. Elaraj: So usually what I tell people is that if they have stage I or stage II thyroid cancer, then their risk of recurrence over the next 20 years or so is in the 20 to 25 percent range. However if they go five years without having any recurrences, then their recurrence risk over that remaining period of time is about 10 percent. So the longer you go without having a recurrence, the less likely it becomes that you will have a recurrence. And so we usually follow people every six months for one to two years and then every year thereafter. And the way that we follow them is by checking something called thyroglobulin, which is a blood test. Do you know about thyroglobulin, Jamie? Andrew Schorr: Jamie, do you know about that? Jamie: Yes, I do. I get tested every six months, which I go Wednesday. Dr. Elaraj: So thyroglobulin is a blood test. It's a protein that normal thyroid cells make, but if a person has had their thyroid gland removed and has had radioactive iodine to kill all of their remaining thyroid cells in the body, then you shouldn't have any cells left that make any thyroglobulin. But if you have cancer that comes back, depending on how closely the cancer cells resemble normal thyroid cells and if they can make thyroglobulin, that would be sort of like the first indication that the thyroid cancer has come back. And then the other way we monitor people is by getting ultrasounds of the neck periodically because we know that papillary thyroid cancer will spread first in most cases. I mean if it's going to spread it usually spreads to the lymph nodes in the neck before going anywhere else, and ultrasound is a very sensitive way to pick that up. Andrew Schorr: Jamie, have those sometimes too, ultrasounds?

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Jamie: I do. Since it's been ten years, I haven't had as many because I was having alternating ultrasound one year and a PET scan the following year, and so it was going about every two years, and then in just the past year and a half, because of the no evidence of disease, I am getting those less frequently. Andrew Schorr: Dr. Elaraj, so I have a question for you then. So we have really given the sense that with papillary thyroid cancer in most cases it's very treatable, and I have read that even if there is a recurrence, that's treatable too, but I would love to hear you put that in perspective for us. Dr. Elaraj: Absolutely. So whenever I have a patient that's first diagnosed with papillary thyroid cancer I tell them that their treatment consists of four parts. And the first part is surgery to remove their entire thyroid gland and to evaluate the lymph nodes that live near the thyroid gland, so in what we call the central compartment of the neck. After surgery most patients, a great majority of patients will receive radioactive iodine, and so that's the second component of therapy. The third component of therapy is something called TSH suppression with levothyroxine. And levothyroxine is the generic name for thyroid hormone. There are multiple brand names of thyroid hormone. And that serves two purposes. One is to make a patient feel normal because without a thyroid gland unless we give them a little bit of thyroid hormone, then they are not going to feel normal and their metabolism won't be normal. But the other purpose that this medicine serves is to actually make them a little bit hyperthyroid. We give them a little bit more than the body actually needs, and the purpose of that is to suppress production of a hormone called thyroid stimulating hormone, or we call it TSH for short, and it's a hormone that the brain makes which is supposed to stimulate the thyroid gland to make more thyroid hormone. We also know that this TSH hormone is a stimulator of proliferation of thyroid cells including cancer cells. And so if we shut the TSH down by giving a patient a little bit more thyroid hormone than we need, then that's taking away even another stimulus or potential stimulus of cancer cell growth if there are any cells left in the body. So that's the third component is levothyroxine to suppress a person's TSH. And then the fourth component is surveillance, and we were talking a little bit about that. And the actual strategies for surveillance vary from institution to institution, and some people get thyroglobulin levels and ultrasounds every so often. Some people will throw in a radioactive iodine scan every so often. Some people will throw in a PET scan every so often. And none of those are wrong. It's very institution specific, although there are some guidelines from some national organizations.

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Now getting to your question about what do you do when it comes back, well, if someone has recurrence of their papillary thyroid cancer, it's usually in the lymph nodes in the neck, and the appropriate thing to do would be to refer the patient to a surgeon to have what we call a lymph node dissection, which is removal of that group of lymph nodes in the neck. And that's done in what we call a compartment oriented fashion. What you don't want to do is find a lymph node that's looks abnormal on ultrasound, get a biopsy of it and say okay, well, I am just going to remove that lymph node because, I'm going to use an analogy that a colleague of mine whom I respect very much uses. He says, you know, lymph node recurrences of thyroid cancer are like ants on watermelon or an ant on watermelon. If you see one, you know that there are more. So if you identify one lymph node recurrence on ultrasound, you know that there are going to be more, and if you go out, if you go and just remove that one suddenly you have created scar tissue, and when the rest of the lymph node recurrences make themselves known, whether that's six months from now or a year from now or five years from now, and you have to go back and re-operate there, suddenly the operation is more difficult and carries a higher risk for the patient because there is going to be scar tissue there. So what I recommend to people who have a recurrence of their thyroid cancer is something called a formal compartmental lymph node dissection. And it just depends on the compartment of the neck in which the recurrence happens. And then typically afterwards people will get another dose of radioactive iodine. Andrew Schorr: Now, with thyroid cancer without a recurrence, and Jamie was talking about the medicine she takes, can someone lead a normal life? And are they at risk for another cancer? Dr. Elaraj: So those are two really good questions. Taking your first question first, can they lead a normal life? Absolutely they can lead a normal life. You know, papillary thyroid cancer carries an incredibly good prognosis, and I usually tell people that their risk of dying from papillary thyroid cancer 25 years from diagnosis is in the five percent range, and so 95 percent of people are doing great 25 years out from their thyroid cancer. Now, it's not a hundred percent, because it is a cancer, but of all the cancers out there it carries an excellent prognosis, and a very indolent sort of course. It's actually interesting that there are published autopsy series, so people who study people who have died of other causes, and they have reported thyroid, this type of thyroid cancer found in the thyroid gland of people who have died of other things in up to 30 percent of people. And they didn't even know it, never had any impact on their life at all. In terms of are they at risk for developing other cancers, well, if they are part of a familial kindred, so I was talking a little bit about this familial adenomatous polyposis syndrome. So if they happen to fall into that category which is very rare, then they are at risk for developing something like colon cancer. There is a little bit of controversy regarding whether or not radioactive iodine itself increases a 7 www.patientpower.info NMH102808/1102/AS/jf

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person's risk for other cancers, and there have been some studies done, usually in Europe they do this where they have got very good population-based registries, where the researchers will look at a population of people who have received radioactive iodine for thyroid cancer and follow them over a long period of time and look to see what other cancers they develop, and then compare them to what is expected for people of similar ages living in a similar part of the country and have found that maybe there is a slight increased risk for some sort of GI cancers, gastrointestinal cancers, and maybe for some hematologic cancers, but it's not conclusive by any means. Seeking a Specialist for Treatment Andrew Schorr: Now, what is the benefit of either seeking treatment from or at least getting a second opinion from someone such as yourself who specializes in this area rather than just going to a general surgeon? Is there a benefit where we are now for going to an academic medical center? Are there clinical trials? Dr. Elaraj: Well, that's a tough question for me to answer because it's conflict of interest I guess, but I will tell you the data. So 50 percent of thyroid operations in the United States are done by surgeons who do other things. That's 50 percent. So only 50 percent of the thyroid operations in the US are done by specialists or people that we call high-volume surgeons who do greater than 50 or so a year, and that doesn't even sound like that many, but that's sort of the number that they have come up with to say you are a high-volume surgeon if you do 50 a year. And there have been some studies that show that higher volume surgeons have lower complication rates compared to lower volume surgeons. And so I think that it's sort of common sense and what I would want for one of my family members is to go see somebody who does this operation a lot. And it can be anybody. You know, there are excellent otolaryngologists who do a lot of thyroid surgery. There are people like myself and my partner, Dr. Sturgeon, and we are both general surgery trained, but we did an extra year of specialized training in endocrine surgery, and so we are high-volume thyroid surgeons. And so I think the bottom line is that you want to go have this done by someone who does it a lot, because the risks of the operation have to do with the nerves that control the voice and the parathyroid glands that control the calcium level in the blood. And there have been publications that show that higher volume surgeons have lower complication rates compared to lower volume surgeons. Andrew Schorr: Thanks for explaining it. And by the way you talked about somebody doing more than 50 surgeries a year. What's your number? Dr. Elaraj: Oh, I do between one and two hundred.

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Listener Questions Andrew Schorr: Oh, okay. That puts it in perspective. Jamie has collected some e-mail questions for us. Here is one from Sherry in St. Louis. She said, "I've been on the same dose of Synthroid since my thyroid surgery 14 years ago. Recently I had to switch to a higher dose. Does this vary as you age or is something wrong? My level seems to be in check with the new dosage." Dr. Elaraj: It doesn't mean that something is wrong. I don't know the answer to the question does it vary as someone ages because I think that the dose of thyroid hormone that any individual patient requires depends on other things. I think that people who gain a little bit of weight tend to need a little bit more thyroid hormone. It could be that her doctors wanted to suppress her TSH a little bit more than it had been suppressed, and so I don't think that it means that anything is wrong as long as this particular patient's thyroglobulin level is undetectable and nothing has shown up in terms of a recurrence on whatever type of imaging studies her doctors choose to follow her with. Andrew Schorr: Here is a question we got from Jeff in Chicago. He writes, "Is it common to have low calcium after a thyroidectomy? And are there symptoms without a blood test? And why does this happen?" Dr. Elaraj: So that's a great question, and that goes back a little bit to one of the possible complications of thyroid surgery. So this gets to something called a parathyroid gland, and "para" means next to the thyroid gland, and we all have pretty much four. And I say pretty much because some people can have fewer than four, and some people can have more than four parathyroid glands just depending on how we developed embryologically. And what they do is they control the calcium level in the blood. And these parathyroid glands, just to give you kind of a visual as to how small they are, if you take a Jelly Belly and cut it in half lengthwise, that's about the size of a parathyroid gland. And they are intimately related to the thyroid gland, sometimes they are located within the thyroid gland, but those glands are at risk during thyroid surgery. And what I usually tell people is that about five percent of people will have problems with low blood calcium after surgery that's temporary, meaning that it will go away within a few weeks or months and may require taking some extra calcium tablets and maybe even some extra vitamin D because vitamin D helps the body absorb calcium. One percent of people will have permanent problems with low blood calcium, so these people would definitely have symptoms. You don't really need a blood test to say, okay, you are having symptoms from low blood calcium. The symptoms have to do with tingling in the fingertips, tingling around the mouth,

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and when it gets really severe, then they can actually have spasming of the muscles. And a blood test of course would confirm that this is going on. And the way it's treated is with a ton of calcium and some vitamin D. Hope for the Future Andrew Schorr: Now, we started our program with our own producer, Jamie Machala, you know, having been treated out the blue for thyroid cancer ten years ago. Jamie, so what would you say? There may be somebody listening who is has just been newly diagnosed with this, with papillary thyroid cancer, and they are trying to put it in perspective, and Dr. Elaraj has done a great job in doing that. But from a patient's perspective anything you would say to them? Jamie: Well, I would have to say that one of things that my doctor told me, because obviously I was young, and it was very scary to hear that, especially right after waking up from surgery thinking it was just sort of a routine medical procedure, my doctor said if you are going to get a cancer, this is probably the best one to have, so that made me feel a lot better. And I think that it's just important to stay on top of it. So make sure that once you are treated you do go see your doctor every six months and really stay on it because I moved around quite a bit, but that was one of the things that I really stayed on top of, going every six months or so and having blood levels tested and having the PET scans and things like that, and it was really very reassuring. You know, at the time when you are being scanned it's not very comforting, but when you come out and your doctor says you have no evidence of disease, it feels really good. So just stay on it I would say. Andrew Schorr: Thanks, Jamie, and we hope you are with us for like the next hundred years. Jamie: Me too. Andrew Schorr: Yes. So stay on it. Thank you, Jamie, for putting this program together and then being willing to share your personal story. Dr. Elaraj, it sounds like there are many, many, many people across America who have been treated successfully like Jamie, and when it comes to papillary thyroid cancer can remain in a close association with the doctors who can help follow them, but have a good expectation to live a good long life. Dr. Elaraj: Absolutely. Absolutely. There are something like, I am trying to remember the number, I think it's well over 300,000.

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Andrew Schorr: That's the number I have seen, yeah. Dr. Elaraj: Yes. Thyroid cancer survivors alive and well in the United States. And I tell my patients the same thing that Jamie's doctor told her, that if this is the type of cancer that you are going to get, this is the one that you want to get because it's very treatable, not just with an operation, but we have really good targeted therapy. If you really think about the radioactive iodine, it's quite clever actually because it takes advantage of the fact that the thyroid cell has a receptor on its surface that takes in iodine. That's how it makes thyroid hormone, and iodine is found in a lot of the foods that we eat in the form of salt. And so it's really taking advantage of the fact that iodine can get into the thyroid cell almost exclusively. There are a few other tissues in the body that can take up iodine, but not to the same degree that the thyroid cell can. And basically it becomes a cancer cell's downfall that it takes up this radioactive iodine, and then the radiation kills it. Andrew Schorr: Whenever we can hear about, you know, killing the cancer cell and leading a normal life, that is good news. Dr. Dina Elaraj, endocrine surgeon at Northwestern Memorial and the Feinberg School of Medicine, thanks for being with us and really putting thyroid cancer in perspective for us on Patient Power. Dr. Elaraj: My pleasure, Andrew. Thank you so much for having me. And, Jamie, very nice to have met you and best of luck with everything. Jamie: Thanks very much. Andrew Schorr: What a great group. Well, this is what we do every two weeks on Patient Power sponsored by Northwestern Memorial Hospital. And our next program is going to discuss diabetes, which of course affects millions and is an epidemic in the United States. And we will have with us Dr. Greg Clark. So if you have questions for that, just send them in to us. You can always e-mail questions to [email protected] I am Andrew Schorr. Remember, knowledge can be the best medicine of all. Thanks for joining us. Please remember the opinions expressed on Patient Power are not necessarily the views of Northwestern Memorial Hospital, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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