Patient monitoring and therapy selection in RAIR DTC

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Marcia Brose, MD: Lori, you’ve talked about this before, but maybe you could tell us concisely what your triggers are for moving from active surveillance to treatment. Do you have a short list in your head? How do you do?

Lori Wirth, MD: This period of active surveillance or monitoring of the disease is very useful in establishing the nature of the disease because there is a very wide variation in the natural history of iodine-refractory DTPs. [differentiated thyroid cancer]. Some patients may progress very slowly over time, and these patients would likely benefit from a long period, or as long as possible, of monitoring the disease and waiting before starting a TKI [tyrosine kinase inhibitor] like lenvatinib. When this patient was suffering from a worrisome disease from the start, this period of monitoring the disease was extremely beneficial for us to know exactly what we are dealing with. Just as the lung biopsy told us exactly what we were dealing with, so we don’t have to second guess ourselves here. It is difficult to define what it is, but there is a clinically significant progression of the disease. I don’t think a tiny bit of disease progression is a big deal. If you see a new lung [metastases] popping up here and there is significant even if it’s not huge lung metastases.

The other thing Bruce mentioned is performance status. If the patients have a performance status of 0, they’re perfectly fine, that’s fine. In the SELECT trial, because of the eligibility criteria, usually when patients had a performance status of 1 versus 0, it was probably because of their thyroid cancer and being symptomatic of their cancer of the thyroid. When we looked at the performance of patients with a performance status of 0 versus 1 in the SELECT trial, the performance status of 0 patients improved and also had better overall survival. We certainly don’t want to wait until patients are symptomatic or nearly symptomatic with their illness before we start.

Marcia Brose, MD: I would totally agree with everything you say. I would add one more thing that I also consider, and that goes back to the importance of looking at the scans yourself, because you get an idea of ​​what you’re seeing and the rhythm of it if you look at the nodules by compared to just reading someone else’s measurement, #1, but also the location. I’ve had patients who only had maybe a centimeter and a half of lymph node here or there in the mediastinum, and that may not have been something that triggered me right away, but I could see the shrinkage starting to happen. That would tell me that it won’t be good behavior even if it’s not that big because it’s going to drop the right upper lobe in this case for this patient. Another area that I’m particularly concerned about is when patients start to have these beads on a string that are along the fissures, either the main fissures, or they have them along the pleural surface, because the scans under – often estimate the tumor burden in these cases. I even had a thoracic surgeon tell me the lung was completely coated in cancer, it just didn’t show.

In addition to now thinking about size and performance status, we also need to consider the location of disease. I would certainly support and support your point about doing this biopsy. Literally just last week I had a patient at the time of progression who had a new liver metastasis, and I went ahead and did a biopsy because I wanted to get the genetics on it and I hadn’t gotten any genetics on the patient, and she had metastatic colon cancer. It’s a fairly common cancer that we always have to be aware of, and I’ve also been diagnosed with non-small lung cancer, so we always have to make sure we know what we’re dealing with.

Bruce Robinson, MD: The other thing I would add too, Marcia, you were talking about looking at scans. Often in selected patients it is rather good that the patients also look at the scan, because when they see a response they are encouraged, and the psychological benefit of that, if they respond of course, is great. If they don’t, the opposite is true, but it helps patients visualize things.

Lori Wirth, MD: It’s also great fun to do with patients, to celebrate those responses.

Marcia Brose, MD: I agree, and I have a patient coming in and she’s still discouraged and has a list of a hundred things that upset her. Then I show him. I always keep track in my notes of when they started, and I’ll go up the scan from their start date and where they are now because maybe once in a while it’s not such a big difference, but in a year and a half there was a huge difference. Then she shuts up and sits down, and she’s like, “Yeah, I’m not going to change anything.

Bruce Robinson, MD:Yes it’s good. I agree.

Marcia Brose, MD: It convinces them. Bruce, you continue to treat your patients and monitor them, don’t you?

Bruce Robinson, MD: It’s correct.

Marcia Brose, MD: When you follow them, how often do you see them?

Bruce Robinson, MD:After the start of the therapy, I remain in telephone contact with them. Then I’d like to see them usually a month later because that’s often when you have to at least start thinking about some sort of dose adjustment, but at the same time you often try to encourage these people to maintain the initial dose of 24 mg. Once they’ve become stable, their blood pressure is well controlled, they seem to have settled down to a dose they can tolerate, and you have proof that their disease is under control, I bring follow-up back to every 3 months, and find that for most people that’s OK. During the COVID-19 pandemic, of course, we’ve had to do a lot of this remotely, telehealth consultations, and it’s been a lot more difficult because it’s not been as easy to get patients scanned as it used to be. COVID-19. And we succeeded, that’s the result, and I often wonder if, in retrospect, maybe we weren’t a little overzealous with our follow-up frequency in digitization. But it only takes one patient to have a bad outcome because an adverse event wasn’t properly managed, and you’re probably challenging yourself then and thinking that those people need to be seen a little more often. Basically it’s monthly for the first 3 or 4 months, then I bring it back to every 3 months.

Marcia Brose, MD: I do something similar. I probably go every 2 months until a year, then I go every 3, but again I give them more leash depending on how they tolerate it. If they swim through, I’ll go every 3 months early.

Transcript edited for clarity.

Martin E. Berry