Establishing Treatment Goals and Monitoring Patients With DTC

Criteria used by endocrinologists/oncologists to establish goals of therapy for patients with differentiated thyroid cancer, and recommendations for active surveillance.

Lori Wirth, MD: Speaking of molecular diagnostics and treatment options, let’s talk a little about treatment. Naifa, do you want to lead this? I think we’ve talked a bit about surgery. We’ve probably touched on that. I think we talked about radioactive iodine, and so we’re already at, unfortunately, iodine-refractory DTC [differentiated thyroid cancer]. So Naifa, where would you start?

Naifa L. Busaidy, MD, FACP, FACE: First of all, just as background because I’m not sure that we mentioned this, in 85% to 90% of differentiated thyroid cancers, surgery is the most important. Resecting the disease is the best chance at making somebody cancer-free. And so, the reason I want to emphasize that is identifying your surgical colleague who is really good and does thyroid cancer surgery is very important, even if the patient has to travel. That cannot be emphasized enough.

The last thing you want to do is harm your patient and leave disease behind. So, see us second. It’s always a 3-pronged surgery, then radioactive iodine. But don’t beat that horse, don’t keep treating with radioactive iodine. So, give the initial treatment, maybe 1 more empiric dose, and then give up, like Giuseppe had talked about. And then giving the patient thyroid hormone, giving them about 2 μg/kg, giving them a little more than their body needs of TSH [thyrotropin] suppression.

Beyond that, that 5% to 15% of patients who would recur, most of them recur in the neck. And so, we are looking at more surgery, not necessarily any more radioactive iodine, but more surgery. So that is important and that cycle keeps going. Beyond that, we’re following patients with their thyroglobulin, their cancer marker. It’s important to measure that at the same time as their TSH levels because that can vary by their TSH levels.

Once you’ve determined that the patient has disease, either biochemically by their thyroglobulin, or by imaging, then the question is, is that going to harm the patient? And of course if you’ve determined like Lori said, that this is refractory to radioactive iodine by the definitions that Giuseppe had mentioned earlier, then there is no cure. It’s important to be stepping back, explaining to the patient, and controlling our own anxiety—the patient feeds off of the physician’s anxiety—that maybe we need to change our mindset that we’re living with disease.

When a patient has residual disease that you’ve identified, either the thyroglobulin’s elevated or they have structural evidence of disease on imaging, which most commonly is in the neck, many of those patients can live with that thyroid cancer there without it being threatening. So, if it’s not progressive, it’s not symptomatic, you make this decision with the surgeon. Even if they’re not in your office or not in your institution, making that phone call is important as to, is this really going to cause harm? Can we do short-term follow-up? You’re not saying goodbye to the patient. You’re following them with imaging every 3 to 6 months initially, and making sure that it’s not growing.

I would advise when you have residual neck disease that you also do imaging of the chest to see that they don’t have distant metastatic disease, which most commonly is in the chest after the neck. Then if the thyroglobulin is rising and you’re not seeing changes in the neck or lung disease, do a PET [positron emission tomography] scan. When thyroglobulin is rising, especially if it’s greater than 10 [ng/mL], PET scans are very helpful. They’re not necessarily helpful in the vast majority of thyroid cancers prior to this. If you have radioactive iodine-refractory disease, if they have disease that’s growing in the neck, have that conversation with the surgeon, surgical resectability. If it’s not resectable or there’s distant disease, then we move on to other discussions about systemic therapy, which we’ll discuss in a second.

Lori Wirth, MD: That’s exactly what I wanted you to talk about.

Naifa L. Busaidy, MD, FACP, FACE: External beam radiotherapy is not very good with structural disease present. There is a role for it, which I’ll come to in a second. But just so we review the data, the retrospective data suggest that when there’s structural evidence of disease and it’s just sitting there and not progressing, that giving them external beam radiotherapy is not very helpful.

The role of external beam radiotherapy is if there’s progressive disease that is growing fairly rapidly, albeit, and the surgeon has said, “I can’t cut this out.” The other role of external beam radiotherapy we use a lot less now, and that’s in the adjuvant setting. So, the surgeon has operated on the neck, whether it’s the first or the fifth time, and he or she’s gotten it down to microscopic level. However, he or she says that we cannot go back into the neck, and so we need to do external beam radiotherapy because we’re at high risk. And that tends to work better in older patients, but we’re not using that in everybody. Again, coming back to that multidisciplinary conversation is so important.

Maria E. Cabanillas, MD: I would argue that we’re using a lot less external beam radiation in differentiated thyroid cancer for the neck than before because we have good systemic therapies now. Where we’re using it more often in differentiated thyroid cancer is targeting a distant metastasis. And so, I think that the role of external beam radiation in the neck for DTC has really changed a lot in the past decade.

Lori Wirth, MD:How about chemotherapy, standard cytotoxic chemotherapy, either with radiation or alone?

Marcia Brose, MD, PhD, FASCO: I would argue that’s now gone the way of the dinosaurs. We really don’t give that at this point. That was 1974 when Adriamycin [doxorubicin] was approved, and it was approved based on x-rays. So, there was progression happening that we couldn’t even see. It was approved in spite of fact that it doesn’t work. At this point we don’t give it unless we are talking about maybe an aggressive anaplastic thyroid cancer that doesn’t have any other treatment options like a BRAF mutation, or we’re giving it with radiation. But that’s really a very select, very small, rare situation.

Naifa L. Busaidy, MD, FACP, FACE: People try to bring up the argument, “Well, your partial response rates were on the order of 15% to 20% with cytotoxic chemotherapy, and your targeted therapies sometimes are that.” But the point is that they’re short-lived, and they have toxicity.

Marcia Brose, MD, PhD, FASCO: And they were progressing, but because it was x-rays and not CT scans, we couldn’t see it. That’s another reason why the PFS [progression-free survival] was twice as long as it probably really is.

Transcript edited for clarity.

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