Transcript:R. Michael Tuttle, MD: Marcia, take me to the opposite end. So, what you heard Naifa talk about was relatively low- or intermediate-risk patients that essentially are surgically cured. You can get all their surgery out, maybe a little radioactive iodine, maybe some TSH, but they’re a surgical cure. What do we do when we’re faced with somebody, they’ve got a nodule in their thyroid, but they’ve got a spine metastasis or they’ve got a hip metastasis? How do we deal with that?

Marcia S. Brose, MD, PhD: Interestingly, some of the patients actually present that way. In fact, they weren’t discovered with a thyroid nodule at all. But now they come in with a pathologic fracture or pain in their back that may have been there for years, especially because thyroid cancer is usually fairly slow growing. So, what you need to do is address the thing that is a medically emergent situation. You need to stabilize the spine, do surgery if you can, and in some cases, they’ll need external beam radiation as well. You need to sort of handle the emergency right away.

R. Michael Tuttle, MD: So, all of that delaying Dr. Naifa’s surgery and radioactive iodine.

Marcia S. Brose, MD, PhD: It doesn’t matter at all because if you think about it, the horse is already out of the barn. You’re still going to do that to control the disease and try to limit the disease. And, in fact, the radioactive iodine will go places including to bone metastasis. So, it’s not that you wouldn’t do it, it’s just that you do need to handle the surgical situation first, whether you need to replace the hip. But, even if you can’t remove it surgically, you definitely need to get external beam radiation. You also have to think about this patient, regardless of what happens with the surgery and radioactive iodine. The one thing I’ll say is disease that goes to the bone tends to go to the bone, and will go to the bone again. Even though we can try to control it—and the radioactive iodine may do a very good job at preventing it—that patient is already flagging themselves for somebody who will probably benefit from bone stabilizers, such as Zometa. And, we tend to plan to give that in there. Now, we may wait until the surgery radioactive iodine is done, but as soon as they’ve presented with bone disease, they have that on their menu, and it will definitely be brought in as soon as the rest of their disease has been taken.

R. Michael Tuttle, MD: It’s part of the process. Some of these patients have a disease that’s not easily resectable. In these high-risk guys, that disease is invading the trachea, it’s in the wall of the esophagus. If the surgeons can get it out… We know they didn’t get all of it out. It tends to be poorly-differentiated, and radioactive iodine is not going to work. Where do we need to start thinking about external beam radiation in that local regional control?

Frank Worden, MD: I think that is kind of a tricky thing with a lot of these patients. In some of it, you’re concerned about the airway, and so we always have them evaluated. Do they need tracheostomies or not? And I think, at that juncture, there is a role for external beam radiation therapy. So, those patients who present with either large mediastinal involvement or the disease in the neck, N3 tumors, start with radiation. And it doesn’t mean we wouldn’t consider radioactive iodine therapy, perhaps for the rest of the distant disease, but to get control of that disease, we definitely would start there.

R. Michael Tuttle, MD: Eric, let me ask you. I’m in charge. The question is, we always take the thyroids out and we always give radioactive iodine. But, in some of these patients, we know radioactive iodine is not going to work. They’re patients with Hürthle cells, they have bad, poorly-differentiated tumors. And I’m taking out a relatively small thyroid nodule that has distant metastasis. Is there any logic to bypassing the thyroid surgery altogether and you just treating with one of these tyrosine kinase or targeted drugs or medicines?

Eric Sherman, MD: Well, what you always have to first consider is that all of these tyrosine kinase inhibitors have toxicities, and no one wants to live their life with that. And once we start it, they’re on it forever. So, even though they have distant metastatic disease, that disease could still be very slow growing and doesn’t warrant treatment at that time. Maybe it does, but a lot of times it doesn’t. And, if that’s the case, you don’t want to start them on a tyrosine kinase inhibitor. It’s actually easier for them to maybe undergo surgery and have it resected. Even when you do want to start it sometimes, you do have to consider local control. You have to decide on a case-by-case basis. I don’t think we have to always automatically go to total thyroidectomy for a half a centimeter nodule in the thyroid. If the person has a 3- to 4-cm nodule on the thyroid—even if we can control it for a while with tyrosine kinase inhibitor, when something starts growing, it’s not going to be the lung nodule that’s going to cause some problems. It’s going to be the tumor invading through the trachea that’s going to cause the problems.

R. Michael Tuttle, MD: Which is clearly the more common thing in this situation, to have a big tumor up front. Marcia?

Marcia S. Brose, MD, PhD: So, the one thing I will balance with that is that when we first started in this, a lot of patients who had neck-only aggressive disease, or even sometimes neck and lung, got surgery and then they would have radioactive therapy, and then external beam radiation. And now, unfortunately, unlike the patients who have had neck cancers that may not survive that long, these patients will often be around 10, 15, and 20 years later. And now they’re having many, many issues related to external beam radiation. I think we, in the last 10 years, have really stepped back from using it routinely. We used to say, oh, external beam or extrathyroidal extension, now we need to clean up the neck. We’re going to irradiate it to make sure it doesn’t come back. I think you’re doing the patient a disservice to do that. And I will say, with the exception of a patient who has bulky disease that’s not resectable, I almost never actually use external bream radiation in an adjuvant way in the neck. I’d rather have them go 10 years and have to have a couple extra surgeries, than end up with problems with stenosis of their coronary arteries and the difficulty swallowing, all of these things that we’ll see.

The other side of that is if they have metastatic disease and they only have a couple of lymph nodes—but it’s not like what Eric was talking about where you’re really worried about it, like if it’s in the thyroid, it’s right next to the airway or if it’s actually invading. I’m not talking about those. They are fairly rare. But it’s quite often that we see patients who have had, say, lymph node involvement and extrathyroidal extension, and now it may even be in a lateral neck muscle. Those patients are probably not going to die from that. I had a young woman who was a mother, and there was even talk about doing a laryngectomy to really clean out her neck and everything. And we held off because we knew we were going to have to treat her distant disease anyway with a kinase inhibitor. So it turns out, if you’re going to end up treating the distant disease anyway, the kinase inhibitors do work in the neck. And how that patient eventually succumbed to her disease was from a distant metastasis. So, I actually have to have a really, really good reason to give external beam radiation, and I try to encourage people to not do it, and to really seek an evaluation by somebody who knows thyroid cancer. Because there’s an art to it and if you cannot give it at all, I think you’re helping the patient.

R. Michael Tuttle, MD: Eric has an opinion on this. This is like every Thursday morning we’re arguing about that. Eric, where are you with this one?

Eric Sherman, MD: I actually disagree. I think with the older radiation techniques, people had a lot of problems with it. And I definitely think—with someone who does not have an experience in doing radiation to the thyroid—you’re going to run into a lot of trouble, and that’s true for all head and neck cancers. You always want someone with a lot of experience with it. But when we look back at our experience using radiation therapy for differentiated thyroid cancers, not anaplastic, we’ve actually found a very good experience, that a very small number of people have long-term toxicities from it. We’ve actually been looking at adding chemotherapy to the radiation.

Marcia S. Brose, MD, PhD: Is this in the adjuvant setting, Eric, or are you talking about patients who had residual disease?

Eric Sherman, MD: So, we’re not talking about adjuvant as you just had a total thyroidectomy and we’re just going to give external beam radiation. We do it occasionally for patients who have had multiple neck surgeries. You’ve had your fifth or sixth neck surgery. The last one was 3 months after the one before, and, in those cases what we’ll actually do...

Marcia S. Brose, MD, PhD: And I agree in that scenario. I’m talking more about in the adjuvant setting.

R. Michael Tuttle, MD: In that truly adjuvant setting. Frank?

Frank Worden, MD: Right, and that’s what I was going to say. In addition to what Marcia said, too, now that we have new targeted agents… And I know we’re going to talk about that a little bit later—one in particular, lenvatinib, has nice responses. I agree, I had a patient very similar to what she described. We decided to give them lenvatinib, and they actually had a very nice dramatic response. So, with the advent of these newer agents coming out that actually induce response, we can use those systemic drugs sometimes in place of radiation. But I do agree, we will give radiation as Eric just described.

Transcript Edited for Clarity