Treatment Approaches and Sequencing Strategies in Differentiated Thyroid Cancer - Episode 5

Defining Radioiodine-Refractory Differentiated Thyroid Cancer

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Key opinion leaders in differentiated thyroid cancer take a moment to define radioiodine refractory disease and consider its implications in establishing a treatment pathway.

Transcript:

Lori J. Wirth, MD: I want to talk briefly for the medical oncology audience on radioiodine [RAI]–refractory disease, because that’s something we weren’t all born knowing and it turns out that in this patient population, it’s very relevant. Medical oncologists are not quite familiar with the definition of RAI-refractory disease. It’s important because sometimes patients with advanced thyroid cancer, who have metastatic disease or locoregional unresectable disease, can respond to radioactive iodine. We want to make sure we’re not denying those patients this much less intensive therapy that’s going to have benefit, at least for time being. For some patients, it’s easy. When patients have known metastatic deposits, they have radioactive iodine, whether it’s a treatment dose or a diagnostic dose of radioactive iodine. If they don’t have an uptake of the RAI on a whole-body scan following the radioactive iodine, they have iodine-refractory disease. If they have some lesions that take it up and some that don’t, they do as well.

It can be a little trickier when patients have an uptake of the RAI: how do we identify which patients have iodine responsive vs refractory disease? According to the ATA [American Thyroid Association] definition, if patients progress after receiving radioactive iodine, even if they did have uptake, that also qualifies as iodine-refractory disease. The ATA guidelines are a good source for the definition, but so are the NCCN [National Comprehensive Cancer Network] Guidelines. I’ll go over the definition of iodine-refractory disease.

Interestingly, we’re talking about various genotypes of differentiated thyroid cancers. There hasn’t been a lot of work done on different mutations that we know are associated with iodine-refractory disease. But there was a good analysis done by Dr [Yansong] Lin from China and her colleagues, recently presented at ESMO [European Society for Medical Oncology Congress], looking at profiling 91patients with advanced thyroid cancer who had iodine-refractory disease and the genotype of those cancers. None of us would be surprised to see that they found more patients of an older age who had iodine-refractory disease. They also had BRAF V600E mutations, with co-mutations, most commonly promotor mutations in the patients with iodine-refractory disease who they profiled. You can also see TP53 and KARS mutations in these patients.

Interestingly, we don’t often think of advanced thyroid cancer as being MSI [microsatellite instability]–high, which would be great to find in a patient because then they may be responsive to immune checkpoint inhibitors. We rarely see MSI-high cases in this patient population. Indeed, of 94 patients, only 1 had MSI-high disease.

That probably fits with what we know. There’s a lot more work to be done profiling large numbers of patients with iodine-refractory disease.

Transcript edited for clarity.