RAI-Refractory Defined

Transcript:R. Michael Tuttle, MD: In many of these distant metastasis patients, we use radioactive iodine and we’ve typically used a lot of radioactive iodine, and when it wouldn’t work, we would use more radioactive iodine. Dr. Naifa, you’re as guilty of this as I am.

Naifa Busaidy, MD, FACP, FACE: No.

R. Michael Tuttle, MD: No, not so much? Help me understand. When do we say enough with radioactive iodine? When is somebody RAI refractory? Not from academic guidelines, but from a real practical standpoint. When do you say ‘I’m done with radioactive iodine’?

Naifa Busaidy, MD, FACP, FACE: Yes. That has shifted a lot. We’ve changed how we’ve thought about that over the years, in terms of what is truly radioactive iodine refractory or when does radioactive iodine truly work, or when should we try it again. In general, the way that I practice is similar to a lot of folks on this table here; we’ll probably give it. The patient has just had surgery. We know that they’re high-risk, that they need the radioactive iodine. We’ll treat them with one therapy, and then look at their posttreatment scan, which is going to be very important because that’s a more sensitive way to look at if their disease takes up radioactive iodine or not. And if I knew, let’s say, from a CT scan of the chest that they had pulmonary nodules or that they had a spine metastases—and I knew that those were definitely thyroid cancer metastasis, but their posttreatment scan doesn’t light up—I’m calling that patient from the beginning, radioactive iodine refractory. That tumor biology is not going to change 2 years from now when they get a new metastases that it’s going to be sensitive to radioactive iodine.

So, I’m calling them from the get-go. Sometimes you’ll treat a patient in that postoperative setting. With that initial dose of radioactive iodine, you don’t see anything on the scan, they don’t have much thyroid globulin—so, you think that they don’t have any disease and something pops up later. In that case, you don’t necessarily know if they’re radioactive-iodine—sensitive or not. You’re guessing that it’s probably refractory to radioactive iodine, but you truly don’t know. It is worth looking at either by giving a diagnostic scan or even giving an empiric dose. It depends on your philosophy. Give an empiric dose of radioactive iodine, but look at that posttreatment scan. If you have any thyroglobulin or any lesions that you’re seeing on a SPECT or a CT scan that you know are thyroid cancer, and they’re not lighting up, call them radioactive iodine refractory and stop. Don’t give them a 500, 600 millicuries of radioactive iodine before you call it just once.

R. Michael Tuttle, MD: Marcia, we share a lot of patients together, and most of our e-mails are asking, do you think this is RAI refractory? You send them to me, so you think they are. What do you need to know to call somebody RAI refractory?

Marcia Brose, MD, PhD: I love it when I have a wonderful history, and there was clearly a nodule there. Radioactive iodine scan was not positive, end of story. Where I’m always e-mailing you to get the information on, is after a patient had radioactive iodine, they maybe had a little bit uptake or didn’t have uptake, but now, they’ve gone for 3 or 4 years and they’ve been fine. I think we always have to remember that radioactive iodine actually is cytotoxic. It actually does kill the cells. So, if they look like they’ve gotten it—in my opinion, that would be a clinical benefit. I’m questioning whether or not that will happen. It’s not uncommon that an oncologist in this country will get sent the patient who may have had 1 or 2 doses. But you really need to know the context. You need to know obviously what Naifa just said, but you also need to know how long they went between radiation doses. Did they get a benefit? And, so often, if I can’t glean that from the history that I’ve gotten or the records of the timing, I’ll just usually e-mail you. Because as a person who’s treating the patient, you usually can tell me, ‘Oh yeah, at this time, they had this and that and that ends the story’. And I’m always very thankful when you e-mail back to me. It saves me a lot of grief. However, it’s not uncommon that sometimes we don’t know. It doesn’t really hurt to stop and say, let’s just make absolutely sure and do a diagnostic scan, and just check it.

The other side of the coin, though, that I think is interesting is that, historically, we get a lot of patients who have had all of these radioactive iodine scans, and not scans and scans, and uptake or not uptake and, ‘Oh, it’s responsive and there’s no uptake’. And then, ‘Oh, if they had a CT scan and it turns out they’ve got 100 nodules’. And now I’m like, ‘Oh shoot, but when were they there?’ So, I think that we’re evolving. And there’s been a paper out—that we’ve talked about—that I think it really benefits patients, especially if the thyroid globulin is positive and the uptake scan is negative, please get a CT scan right after the radioactive one with contrast. Because if you do it after the iodine, you’re not going to give them iodine for a while, you can get the contrast. And at least get one scan, because otherwise, you’re only going to see what you’re looking for and you’re not going to see what we need to know. And so you need to have that complementary.

R. Michael Tuttle, MD: It’s that structural piece you guys always want. Eric?

Eric Sherman, MD: And, there’s definitely also cases where we don’t even need iodine or to do an iodine scan to know they’re refractory. So, we know that the chance of them being radioactive-iodine—sensitive is adversely related to FDG avidity on a PET scan. And, we’ve had a few patients—especially with Hürthle cell—where they’ve had FDG avid tumors that SUVs were 50, 60, or 90. And there really is absolutely no reason to even go through a radioactive iodine scan for these patients. They’re not going to have a benefit for it. We’ve been putting more and more into our studies that the FDG-avid disease really doesn’t even need to be proven to be RAI refractory to radioactive iodine, that that alone is necessary. And it’s also sometimes even with very poorly-differentiated thyroid cancers, that they even might be positive on the RAI scan. Mark Sabra put out a paper where it really showed, that if you give these patients radioactive iodine, you really don’t have any benefit. I think you have to go beyond just what the iodine scan shows. There’s other factors that are out there that really tell us that this is a person whose disease really shouldn’t be getting iodine, and we really need to be looking at systemic therapy right away.

R. Michael Tuttle, MD: It’s complicated because you can get enough radioactive iodine in a tumor to make it positive on scan, and still not be tumoricidal. Frank?

Frank Worden, MD: Yes. I was going to say the same thing that Eric did. Sometimes you can just tell the aggressive nature of the tumor, the extent of disease, and you get a PET, and the PET is positive. Instead of sending them back to you for RAI treatment, we just deem those people refractory up front.

R. Michael Tuttle, MD: A combination of functional and structural.

Transcript Edited for Clarity