Turk Discusses Modern Thyroid Cancer Pathology and Management

Andrew Turk, MD

Andrew Turk, MD

For thyroid cancer, it is often difficult to determine the severity of malignancies for thyroid nodules using cytology samples. For oncologists, this makes treatment decisions impossible because molecular testing and diagnostics are how physicians select the best treatment for each patient.

The National Comprehensive Cancer Network (NCCN) has updated guidelines for molecular testing in thyroid cancer to help oncologists better classify the disease, access risk, make prognoses, and predict the treatment response and toxicity. Additionally, physicians will have more information to decide on a treatment. The most updated guidelines for thyroid carcinoma recommend molecular testing to determine any potential actionable mutations especially when considering administering systemic therapy, particularly targeted therapies, or participation in a clinical trial.

Speaking to the relevance of the NCCN guidelines in thyroid cancer and the current landscape for molecular diagnostics, Andrew Turk, MD, assistant professor of pathology and cell biology, Columbia University, gave a presentation at the3rd AnnualCongress on Oncology and Pathology, hosted by Physicians’ Education Resource, LLC.

In an interview withTargeted Oncology, Turk discussed his presentation as well as the current state of molecular testing for thyroid cancer and the future of testing and diagnostics.

TARGETED ONCOLOGY: What are the key takeaways from your presentation?

Turk:The main takeaway is going to be how to triage nodules whose malignant potential is considered to be in-determinant on the basis of cytology sampling. That triage is mediated on the basis of molecular testing and molecular diagnostics.

I'll start [my presentation] with a brief review of the pathology landscape—just looking at the morphology of the different diagnoses because I think that there are more players in that field than papillary carcinoma and I think it's important to start with a brief reminder. Other than the short histologic review, I'll [mostly] be focusing on the guidelines and the molecular diagnostics.

TARGETED ONCOLOGY: Why is it important to have a thyroid cancer session at a meeting like this?

Turk: Thyroid cancer is extremely common, it is, in fact, one of the most common forms of cancer. In the vast majority of patients, the disease behaves in a very indolent fashion. So, many people don't require aggressive therapy—chemotherapy, radiotherapy, or precision-type therapies. However, a couple of things are happening in the world of thyroid cancer.

For one, new diagnostic categories are emerging. So those warrant discussions so that oncologists and pathologists know how to make those diagnoses and treat those patients. For another, whereas, in the vast majority of cases, the disease behaves in an indolent fashion, there is a subset of patients that have much more aggressive disease. And it's important to discuss those patients and those scenarios so that in those unlikely events, patients are managed appropriately.

TARGETED ONCOLOGY: What is the appropriate way to manage disease in patients with indolent thyroid cancer?

Turk:Very little is required. There are some high-risk parameters such as, extra-nodal extension of nodal metastasis, the staging parameters of the disease that will warrant additional forms of therapy, like surgery of the other lobe of the thyroid or treatments like radioactive iodine. But, again, it's only very rare patients that require conventional or precision-type chemotherapy.

TARGETED ONCOLOGY: What are some of the features that help you distinguish between indolent patient and others.

Turk:The histologic type of cancer. The most common forms of thyroid cancer are the ones that tend to behave in a less aggressive fashion, like papillary thyroid carcinoma. Forms like medullary thyroid carcinoma and anaplastic carcinoma can be, or are usually, extremely aggressive. So, histologic type is one feature that determines how aggressively a cancer is expected to behave. Another one is the stage of the disease. For instance, whether there are nodal metastases or, more importantly, whether there are distant metastases.

TARGETED ONCOLOGY: How prominent is molecular testing within the thyroid cancer community?

Turk:My answer can be applied to all molecular diagnostics and all molecular pathology in that it's a work in progress. The testing period is pretty new. It's an even newer development that molecular testing is standard of care. So, we have relatively little data now on which we're making these decisions. And I think as molecular testing becomes more standard and more routine, we'll know more because we'll have larger numbers of patients with more years of follow-up.

TARGETED ONCOLOGY: Are there any potential targets in thyroid cancer that could be matched with targeted agents?

Turk: That's a pretty well-established thing and continues to evolve. It's relatively recent news that the FDA has now approved 2 agents, dabrafenib (Tafinlar) and trametinib (Mekinist), for the most aggressive form of cancer, anaplastic thyroid carcinoma, which has been shown to harbor a specific mutation in theBRAFoncogene. So, there is legitimate and authentic FDA-approved precision therapy in thyroid cancer.

Another example that doesn't necessarily depend on molecular diagnostics at this point is medullary thyroid carcinoma. There are targeted agents that interact with theREToncogene when medullary carcinoma has metastasized to distant sites, but at the current stage, that doesn't depend on molecular findings.

TARGETED ONCOLOGY: Are there any practice-changing developments that have come up in the area of thyroid cancer?

Turk:In the world of precision medicine, the approval of those 2 agents forBRAF-mutated anaplastic cancer [dabrafenib and trametinib] is the most significant development in the world of thyroid cancer currently. 

TARGETED ONCOLOGY: What do you think should be accomplished in thyroid cancer in upcoming years?

Turk:I think getting everyone onto the same page in terms of which patients undergo molecular testing and the proper incorporation of molecular diagnostics into patient management. This has been fully incorporated into the NCCN guidelines, but I think at the current stage there's probably variability from academic centers to community practices in terms of how knowledgeable both the ordering physicians and pathologists are about these guidelines and to what extent they're implemented. So, I think making the existing guidelines truly universal in terms of physician awareness and implementation is the [next] frontier.

Reference:

1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Thyroid Carcinoma. Version 1.2019. Published March 28, 2019. https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed June 26, 2019.