Imaging, Profiling, Targeted Therapies Drive Advances in Thyroid Cancer

Geoffrey D. Young, MD, PhD, FACS

In recent years, advancements in imaging technologies and molecular profiling for thyroid cancer have significantly improved the detection and monitoring of the disease.

Imaging technologies, such as ultrasound and PET scans, have advanced, aiding in diagnosis and surgical planning, and biomarkers, particularly BRAF mutations, have shown to be crucial for diagnosis and targeted therapy.

Treatment advancements also have been notable, including the development of targeted therapies like tyrosine kinase inhibitors and BRAF/MEK inhibitors, and immunotherapies that are increasingly available for patients with metastatic or poorly differentiated thyroid cancers. For patients with BRAF mutations, there are now specific therapies tailored to this genetic alteration that can aid in treatment.

Additionally, clinical trials continue to explore new options, especially for aggressive cancers like anaplastic and medullary thyroid cancers. Although trials for well-differentiated thyroid cancers are limited due to generally favorable outcomes, there is growing interest in the role of active surveillance for small, slow-growing tumors, potentially reducing the need for immediate surgical intervention in some cases.

In an interview with Targeted Oncology^TM, Geoffrey D. Young, MD, PhD, FACS, chief of the Division of Head and Neck Cancer Surgery at Miami Cancer Institute, discussed the many advances in thyroid cancer, highlighting what a community oncologist should be aware of.

Thyroid cancer, medical 3D illustration, front view: © Axel Kock - stock.adobe.com

Targeted Oncology: What are the latest advancements in imaging technologies for thyroid cancer detection and monitoring? How often are these recommended for patients?

Young: The majority of imaging for thyroid cancer relies on ultrasound. Ultrasound, just like any kind of technology, gets better and better as time has progressed. Now, not only are ultrasounds clearer and easier to use, but they are also more readily available. A lot of doctor's offices, endocrinologists, or surgeons have these in their office and are able to utilize them. I think that has been a very nice component of it.

Nuclear imaging is part of thyroid cancer that has also progressed. We have better technologies with SPECT imaging that can put the nuclear medicines with the CT scan, so you get a better anatomic representation of where the disease is. PET scans usually rely on radioactive sugar as the contrast. You can use different isotopes of different compounds in a PET scanning capability to look at disease, and this becomes very important in the metastatic disease setting as well. I think that we have had the basic tools for imaging for thyroid cancer that have technologically advanced and combined to provide more specific and better-quality imaging that helps in not only the diagnosis, but in surgical planning, etc, for these cancers.

Are there new biomarkers being used to identify high-risk thyroid cancers or to monitor disease progression? If so, how accessible are these tests?

I think from a biomarker standpoint, we did a lot of research looking at BRAF mutations and thyroid cancer, and it is helpful to know these mutations once the patient is diagnosed, and they are also helpful in the diagnosis of thyroid cancer. What has really come out of it is that initially, to diagnose thyroid cancer, all we had was cytology. We looked at what the cells looked like under a microscope. When looking at a small smattering of cells that you get from a fine needle aspiration, which is usually what is ordered for a thyroid nodule that has concerning features. It is often difficult to tell if there truly is cancer there. Those kinds of benign cancers would cause a struggle for a lot of the cytopathologists who are reviewing these.

In the past decade or more, we have had the advent of molecular genetic profiling of these tumors to give a malignancy risk. So, what is the likelihood that this is benign vs malignant? There have been a lot of biomarkers and specific genes have been identified as part of those paradigms in what they are looking at, as far as genetic composition of these nodules to identify whether they are malignant or not. I think because of that, there are multiple companies that do this, and a decent amount of cytology is now referred out for molecular testing to help in diagnosis.

In treatment, it is a little bit of a different story. Mainly, molecular profiling and looking for specific gene mutations for your variety of follicular or papillary, well-differentiated thyroid cancers has not really gained ground in utility as far as changing what we do. Now, for fully differentiated anaplastic tumors, it has been a big change in what we do. Patients with BRAF mutations in those tumors can get the appropriate targeted therapy, and we now are able to increase lifespan in some of these most deadly forms of thyroid cancer solely due to gene profiling and targeted medicine for them. It is very important in that role. There have been several new compounds that have come out in medullary thyroid cancer, which can also be hereditary, that are targeted to specific mutations. But we do not have circulating tumor markers other than thyroglobulin, which really is not a specific, targetable compound, but also, is something we can use to follow for recurrence of thyroid cancer in the blood.

Are there any promising targeted therapies, immunotherapies, or combination therapies being developed for thyroid cancer you can discuss?

Mainly in the more advanced states, so either in metastatic disease or for those poorly differentiated anaplastic cancers, we now are having more forms of therapy based on identified targets. Patients, even with metastatic papillary cancers with BRAF mutations, might be eligible for some targeted therapy in addition to some of the other tyrosine kinase inhibitors that are available to treat patients with metastatic disease. That is an ongoing endeavor in the treatment of all cancers, including thyroid cancers.

What are some of the current clinical trials that patients with thyroid cancer might be eligible for?

There is not a tremendous number of clinical trials for well-differentiated thyroid cancers. That is probably a good thing, because it means that patients do so well that there is not a lot of need for change. However, in the patients that do not do well, the ones that develop metastatic disease, the poorly differentiated anaplastic, and in some of the medullary cases, I think that we have seen an increase in the need for clinical trials in those arenas. There are some trials for anaplastic and poorly differentiated for sure, and there are some for medullary. There are some clinical trials around for well-differentiated thyroid cancers, but not as many as there are in other cancers.

Now, there also is an interesting take on things, where there are some institutions that are doing clinical trials looking at observing known thyroid cancers and watching small thyroid cancer. These are based on studies that have been done, mainly in Asia, showing that long-term monitoring of thyroid cancers, active surveillance, and so forth, shows that the disease rarely propagates to the point where an intervention is required, and in enough patients where these studies have shown that long-term surveillance of certain thyroid cancers may be acceptable. This is something we are looking into at various institutions in [the US] as to the role of active surveillance of thyroid cancers and which patients might benefit from that. But the mainstay of the treatment of thyroid cancer is still surgery, and so that is why those things are being undertaken in more of a clinical trial scenario.

Overall, what should a community oncologist know about the growing advancements for thyroid cancer treatment?

As with anything in medicine, this is a constantly evolving field. The nice thing about cancer is we have great guidelines from various different societies. The [American Thyroid Association (ATA)] has wonderful recommendations for thyroid cancers, how much surgery we should do, [and] when to give radioactive iodine.

If we look at the trends in those guidelines, it has been doing less rather than doing more. So, maybe performing hemithyroidectomy where we used to perform totals in certain patients meeting certain criteria, or maybe not doing radioactive iodine in patients where we used to do radioactive iodine. That evolution of a “less is more” attitude has come through in thyroid cancer. Now, again, a patient is a patient and not a guideline. We have to always look at the particular patient's situation and make sure that [treatment fits] in with the guidelines [and also fits] in with [the patient’s] comfort, the level of care being recommended, and how aggressive they want to be.