Case Studies in Thyroid Cancer - Episode 6

RR-DTC: Molecular Testing Considerations

Marcia Brose, MD and Lori Wirth, MD, discuss molecular testing considerations in patients with radioiodine-refractory DTC.

Lori Wirth, MD: Let’s assume that this patient has iodine-refractory disease established, perhaps by another iodine treatment or scan, and she’s got lung metastases. There is some interval growth on the lung metastases over a relatively short period of time, 3 months. Marcia, if the NGS [next-generation sequencing] testing hadn’t been done, would you be doing it now? Would you have wanted it to be done when she was first diagnosed and had her surgery and had that high-risk disease? When is the best time to do molecular testing in these patients?

Marcia Brose, MD: I think that it changes a little bit based on when the patient shows up in my office. Some patients have had some molecular testing done even at the time of their fine needle biopsy. Some patients have had nothing and it’s right after their surgery, and other people have had nothing and it’s 10 years later. The reality of when I test is mostly that I need to get the test. Most of the time I don’t have the choice of when to do it because it’s more determined by when they show up. But my goal is to get that information prior to them needing systematic therapy. There are certainly enough indicators in this case that this patient’s heading that way. Systematic therapy at this point, we’ll get into, there are therapies that might be determined based on the molecular signature. Knowing what those options are going to be ahead of time may help me choose which therapies I would choose in the first line, second, and so on. I do want to get molecular testing at this point. We are talking about somatic testing, and it really is used for treatment planning going forward.

Lori Wirth, MD: You do it before the first-line treatment if you can.

Marcia Brose, MD: Well, I’ve started to only because there are some mutations, or more gene fusions, in differentiated thyroid cancer. If there’s a gene fusion with RET or a gene fusion with NTRK, I might consider doing targeted therapy for those 2 gene fusions before using what I would consider my standard first-line therapy. I would want to get it now for sure, but my point is, if you’re going to think about getting systemic therapy, no time is too early. Knowing that information helps me plan.

Lori Wirth, MD: You mentioned RET and NTRK fusions. She has a BRAF V600E mutation, so just quickly, first-line dabrafenib plus trametinib?

Marcia Brose, MD: What I was saying was for somebody who I didn’t know had a BRAF, because that brings up the point that people rarely have more than 1 of those alterations, in the case that somebody didn’t have that molecular testing right away. The question about using BRAF-targeted therapy is the one that I probably do not put before the systematic therapy. The reason for that is that the data really say that lenvatinib activity and response rates are far superior than vemurafenib or dabrafenib. The data are clear that patients are going to do better, get bigger responses and longer progression-free survival with the VEGF receptor inhibitors, mostly lenvatinib, which is my go-to first-line therapy. I want to know that that’s an option, but that would likely come second or third line at this point.

Lori Wirth, MD: Marcia, I agree with you. I thought that’s what you were going to say, which is why I asked you the question because I agree with you.

This transcript has been edited for clarity.