The Importance of Identifying Genetic Alterations in Thyroid Cancer

EP: 1.Identifying NTRK and RET Alterations in Differentiated Thyroid Cancer

EP: 2.Challenges for Thyroid Cancer With RET and NTRK Alterations

EP: 3.Treatment Options for NTRK and RET Alterations in Thyroid Cancer

EP: 4.Combating Resistance Mechanisms to Treatment in Thyroid Cancer

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EP: 5.The Importance of Identifying Genetic Alterations in Thyroid Cancer

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Next-generation sequencing for patients with advanced thyroid cancer is notably important, particularly those who are no longer responsive to radioactive iodine treatment.

Next-generation sequencing can be performed on tissue samples (either initial tumor or metastasis) to identify genetic alterations in the cancer cells. This should include analysis of both DNA and RNA, as some alterations might be missed by DNA-only tests. If a test finds specific alterations, like NTRK or RET mutations, targeted therapies are available. These therapies are highly effective and well-tolerated compared to more general drugs.

However, due to the less common use of these targeted therapies, collaboration with pharmacists is crucial. Pharmacists can help monitor patients for potential side effects that might not be routinely checked in standard bloodwork.

The ultimate goal is to identify these genetic alterations quickly and get patients on the most effective targeted therapy available for their specific situation.

Here, Lova Sun, MD, MCSE, assistant professor at the Hospital of the University of Pennsylvania, discusses the important of next-generation sequencing for patients with thyroid cancer.

Transcription:

0:05 | It is important in patients who are metastatic, [are] beginning to be, or are refractory to radioactive iodine such that it is not a treatment option for them anymore to make an effort to perform next-generation sequencing, either on the initial thyroidectomy specimen or a biopsy of a metastatic site, and then perform a broad DNA- and RNA-based next-generation sequencing panel to identify these alterations, especially fusions, which can be missed by DNA-only based panels. It is important to incorporate RNA-based methods to make sure that we capture these alterations.

0:51 | If you are lucky enough to find an alteration in NTRK or RET and really confirmed that this is a disease-associated variant, not something like a synonymous alteration or uncertain significance alteration, I think that the recommendation is to opt for the corresponding targeted therapy, which as I have mentioned, have excellent efficacy as well as tolerability over a mutation-agnostic, multitargeted [tyrosine kinase inhibitors (TKIs)].

1:19 | These are relatively uncommon alterations compared to BRAF, for instance, in thyroid cancer. These are not drugs that we are using all that commonly. I think it is important to, if possible, recruit assistance and collaboration with pharmacy colleagues who can make sure that we are monitoring patients appropriately. For the [adverse] effects that are a little idiosyncratic sometimes, not necessarily things that we always check on our toxicity labs, for instance, to make sure that we're administering these drugs safely.

1:54 | Certainly, the most important thing is to find these alterations, and then as quickly as we can, start patients who have progression on the corresponding targeted agent that has been shown to be efficacious in that setting.