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Clinical

EIS-21-TTD0559 - /clinical/thyroid

In an interview with Targeted Oncology, Yuri E. Nikiforov, MD, PhD, discussed what led to the reclassification of NIFTP and the incidence of thyroid cancer in patients.

Reclassification as NIFTP Helps Reduce Over Treatment of Thyroid Cancer  

In an interview with Targeted Oncology, Aime T. Franco, PhD, discussed the molecular landscape of pediatric patients with thyroid cancer and the presentation she gave at the 91st Annual Meeting of the American Thyroid Association.

Molecular Targets Making Headway in Pediatric Thyroid Cancer Research

During a Targeted Oncology™ Case-Based Roundtable™ event, Marcia S. Brose, MD, PhD, discussed the case of a patient with advanced thyroid cancer who was previously treated with radioactive iodine and has an NTRK fusion alteration. 

Roundtable Discussion: Brose and Participants Review NTRK Inhibitors vs Other Therapies for Advanced Thyroid Cancer

In an interview with Targeted Oncology, Everett E. Vokes, MD, discussed precision oncology for head and neck cancer and how the molecular biology of head and neck cancers is an opportunity for new investigations and treatment development. 

Precision Oncology Inches into Head and Neck Cancer Paradigm

In an interview with Targeted Oncology, Melanie Goldfarb, MD, MSc, FACS, FACE, highlighted the importance of long-term survivorship care and the quality-of-life aspects of patients with thyroid cancer.

Survivorship and Quality-of-Life Play Important Roles for Patients With Thyroid Cancer

Yuri E. Nikiforov, MD, PhD, professor of pathology and director of the Division of Molecular Anatomic Pathology at the University of Pittsburgh School of Medicine, discusses the reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), which has significantly influenced the thyroid cancer space.

Prior to 2016, the tumor, an encapsulated follicular variant of papillary thyroid cancer (EFVPTC), used to be called a type of cancer. Patients with EFVPTC were typically treated with thyroidectomy or radiation, conventional thyroid cancer treatments. However, researchers found these tumors to be low-risk and deemed lobectomy to be a usually sufficient treatment.

As a result, investigators conducted an international, multidisciplinary, retrospective study to further evaluate the tumor type. The panel of the study concluded that this type of tumor was indolent and ended up renaming the tumor, NIFTP.


The reclassification happened in 2016. It was preceded by about 2 years of work of the international groups that I had privileged to organize and lead. The reason for a classification was that we knew for many years that there is a group or a type of thyroid cancer that is extremely indolent. The patients do very well, and patients don't die of this disease. Yet, we were diagnosing it at an increasing rate. Patients were treated very aggressively. They were treated with the removal of the thyroid and given radioactive iodine. We felt that this is an overtreatment for these patients.

So the international group of physicians got together and looked at all of the available information, and based on the data, it offered this data-driven reclassification of this cancer, and removed the word cancer, and called them as a non-cancerous or NIFTP. That in essence was needed in the field, and that was why this happened in 2016.

Videos

Yuri E. Nikiforov, MD, PhD, discusses the reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, which has significantly influenced the thyroid cancer space. 


News

Discussing the Reclassification of NIFTP

Melanie Goldfarb, MD, MSc, FACS, FACE, Center for Endocrine Tumors, Providence Saint John's Cancer Institute, discusses the importance of long-term survivorship care and its correlation with quality-of-life in patients with thyroid cancer.

Quality-of-life is a big word that has a lot of meaning for patients with cancer. Quality-of-life is a specific and multidimensional type of patient-reported outcomes, and measuring one's quality-of-life includes evaluating the emotional, psychosocial, and physical aspects of a patient.

According to Goldfarb, if a patient with thyroid cancer is surviving, they could still have negative aspects going on around them. As a result, it is important that these things, whether they be physical or emotional, be addressed and dealt with by experts in order to ensure a patient is getting the best care and has the best outcomes.

Quality-of-life is a big and all-encompassing word. There are emotional, psychosocial, and physical things that have to do with it. There are general measures of quality-of-life that one fills out with some questions and that talk about it, and then there are also some thyroid-specific quality-of-life measurement tools which can be used. There are some differences based on age of patients, based on extensive surgery, based on if they get radioactive iodine, and so on and so forth. But across the board, at least in the direct aftermath of getting care, there usually is a dip in quality-of-life.

For many people, that bounces back up to normal after a period of time or about a year, but some of that has to do with, did they have any complications from surgery or are they worrying about other things? All of that comes into it. Quality-of-life is a big word. In general, it is more appropriate to talk about the specifics of it, but we use it as an all-encompassing word.

Melanie Goldfarb, MD, MSc, FACS, FACE, discusses the importance of long-term survivorship care and its correlation with quality-of-life in patients with thyroid cancer.

Links Between Quality-of-Life and Survivorship in Thyroid Cancer

Melanie Goldfarb, MD, MSc, FACS, FACE, FSSO, Center for Endocrine Tumors, Providence Saint John's Cancer Institute, discusses the importance of survivorship and providing care to patients with thyroid cancer.

There have recently been multiple articles and symposiums highlighting the importance of survivorship for patients with thyroid cancer. According to Goldfarb, survivorship is defined as the time from diagnosis.

It is important to highlight this topic as long-term survivorship care aids in reducing anxiety, emergency hospital visits, and health care costs, for patients across various cancer types, including thyroid cancer.

There's been a couple different articles and symposiums proposed and finally [last] year, we [had] a full survivorship symposium, which is really exciting. It’s important because anybody that gets thyroid cancer is a thyroid cancer survivor, so survivorship is from the time of diagnosis. Even more so for thyroid cancer patients, they live a lifetime for the most part, so every year there's more and more thyroid cancer survivors.

 But even if you're surviving, that doesn't mean that you don't have physical, emotional, psychosocial, and things going on that are important to be acknowledged, addressed, and dealt with. In the cancer community until 10-15 years ago on all cancers, it was like, great, let's keep you alive. But now as more and more people are survivors and living longer, what survivorship means and all the other things are coming to the forefront.

Same thing especially in the thyroid world, because they're not usually taken care of in the oncology space. All of these survivorship things are not always available or not always brought up. [Experts say,] you have thyroid cancer, great, you're done, and don't acknowledge that a lot of the patients have a lot of other things going on.

Melanie Goldfarb, MD, MSc, FACS, FACE, FSSO, discusses the importance of survivorship and providing care to patients with thyroid cancer.


Defining Survivorship in the Thyroid Cancer Space

Larisa Greenberg, MD, a medical oncologist at Allegheny Clinic Medical Oncology of Allegheny Health Network, discusses how the treatment landscape for metastatic thyroid cancer has moved forward in recent years.

newer options are selected based on molecular profiling

 This testing will help identify targetable abnormalities, which can be treated with tyrosine kinase inhibitors or multikinase inhibitors, says Greenberg. Some abnormalities that can be found in patients with metastatic thyroid cancer are 

 In the last 5 to 10 years, we made incredible progress in treatment of metastatic thyroid cancer. The first thing that happens when we have a patient who has metastatic disease is we have to evaluate the performance status of the patient or comorbidities.

 We also must look at the rate of growth and size of metastatic lesions. If a patient is asymptomatic, the size of the lesions or metastatic lesions is less than 2%, and the rate of advancing of metastatic disease is less than 20%. Over a period of years, we would tend to observe these patients and not to start them on any specific treatment. However, if patient is symptomatic and the rate of the progression of the metastatic disease is more than 20% over a period of year, then we have to think about different treatment options.

Larisa Greenberg, MD, discusses how the treatment landscape for metastatic thyroid cancer has moved forward in recent years. 

Advances in Metastatic Thyroid Cancer

Aime T. Franco, PhD, assistant professor and investigator with the Center for Childhood Cancer Research at Children's Hospital of Philadelphia, discusses how recent research has explored the difference between pediatric thyroid cancer and adult thyroid cancer at the 91st Annual Meeting of the American Thyroid Association.

According to Franco, a key difference is that pediatric thyroid cancers can be classified in 3 groups: those associated with 

 mutations, and those associated with oncogenic fusions. Oncogenic fusions are more common in pediatric cancers than adult thyroid cancers and tend to be more invasive with greater risk of recurrence and metastasis.

Though pediatric thyroid cancers are rare in the general population, Franco says that multicenter studies through collaborations and consortiums have enabled researchers to identify these 3 subtypes. Studies have also allowed researchers to learn more about the progression of the disease. More research is needed into what can be done to treat recurrent disease. A key question is whether pediatric patients need to be treated like adult patients as they mature.

 In recent years, what's been so unique is for us to start to understand the fact that pediatric thyroid cancers tend to look like there are 3 main groups based on their mutations, whether they're driven by 

 mutations, which we see in adult tumors, whether they're driven by 

 mutations, which we also see in the adult tumors, but interestingly, in pediatrics, we see a lot of fusion-driven tumors that are driven by oncogenic fusion events. Although we see these in the adult cases, they tend to be much [rarer] than they are in the pediatric space. In the pediatric space, they represent their own bucket.

 These tumors we're seeing, it looks like they behave differently; they can be more invasive [and] they tend to have a greater risk for recurrence and for metastasis. We're still working and collaborating [not only] within our group, but in many others to expand the number of samples we've looked at, because thyroid cancer in the pediatric setting is still a rare cancer. It is difficult to get real power in large studies without doing multi-institutional studies, which is exactly what we're doing now, and starting new collaborations and consortiums. But it looks like pediatric tumors really kind of fall in these 3 buckets, whereas the adult tumors tend to fall in 2 buckets.

This is going to change how we think about treating the disease as well as stratifying these patients for their long term follow up and how we think about it, again, as this lifespan disease. And as these pediatric patients start to become adults, or are their tumors going to, if they have persistent disease, continue to act like pediatric tumors, or are they going to act like adult tumors? And that's an open-ended question at this point.

Aime T. Franco, PhD, discusses how recent research has explored the difference between pediatric thyroid cancer and adult thyroid cancer at the 91st Annual Meeting of the American Thyroid Association.

Stratifying Patients With Pediatric Versus Adult Thyroid Cancer

Aime T. Franco, PhD, assistant professor and investigator with the Center for Childhood Cancer Research at Children's Hospital of Philadelphia, provides an overview of her discussion regarding the molecular landscape of pediatric patients with thyroid cancer at the 91st Annual Meeting of the American Thyroid Association.

According to Franco, the thyroid cancer space tends to be underrepresented in the research spectrum due to low mortality rates associated with the disease and available treatment options.

However, there is always more to be learned, especially in examining the differences between pediatric and adult patients with thyroid cancer.

I plan to discuss some of the new findings we have looking at the genetic and molecular landscape of pediatric thyroid cancers, and how this has improved our understanding and lended insight into how pediatric tumors are similar, but also very dissimilar to adult tumors, how we can personalize and specialize our approach to our pediatric patients compared to our adult patients. But also, to get us to start thinking about the fact that pediatric patients become adult patients, and how is that going to change over their lifespan?


We don't have all those answers yet, but I think this is something we need to start thinking about in the clinical spectrum. Not only the immediate diagnosis, but what are the long term repercussions and how do we start to think about pediatric thyroid cancer as a lifespan disease and not just something that happens only during childhood.

Aime T. Franco, PhD, provides an overview of her discussion regarding the molecular landscape of pediatric patients with thyroid cancer at the 91st Annual Meeting of the American Thyroid Association.


Conference News

Further Research Needed to Evaluate Peds vs Adults With Thyroid Cancer

Krzysztof J. Misiukiewicz, MD, associate professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai and clinical director of the Center for Personalized Cancer Therapeutics at the Tisch Cancer Institute, discusses when targeted therapy may be used for patients with 

Misiukiewicz says that patients with thyroid cancer will first receive surgery and/or radioactive iodine therapy. Those who continue to progress following total thyroidectomy and receiving radioactive iodine need further treatment. Genetic testing can reveal potential targets for therapy including 

, which have different recommended regimens.

 fusion, are iodine-refractory, and have no alternative treatment options are eligible for the NTRK inhibitors larotrectinib (Vitrakvi) and entrectinib (Rozlytrek). These therapies are approved for patients with any solid tumor with an 

 fusion, which can also include salivary gland tumors and soft tissue sarcoma.

According to Misiukiewicz, larotrectinib would be his preferred next line of therapy for any patient with iodine-refractory thyroid cancer with an 

 fusion based on the efficacy seen with NTRK inhibition.

 In thyroid cancer, we treat patients [who] are iodine-refractory, meaning that they underwent total thyroidectomy; they underwent treatment with radioactive iodine and for any reason, those treatments were not effective, and the cancer is still progressing, so we label those patients as iodine-refractory patients. In those situations, those patients are being referred to me, where I do first genetic testing. And then I would consider treating those patients with larotrectinib. So they have to have evidence of progressive cancer that hasn't responded to previous treatments such as surgery or radioactive iodine.

-positive disease, I prefer targeted therapy. Currently we have 2 drugs on the market that are approved; my preferred drug is larotrectinib. That is approved for 

-mutated patients. And this is the drug that usually I choose when I have patients with the 

Krzysztof J. Misiukiewicz, MD, discusses when targeted therapy may be used for patients with NTRK-positive thyroid cancer. 

When to Use Targeted Therapy for Iodine-Refractory Thyroid Cancer

Yuliya Mikheeva, MD, PhD of Saint-Petersburg State University, discusses the many challenges oncologists face in treating patients with anaplastic thyroid cancer (ATC) harboring BRAF 

Due to ATC being an aggressive cancer with a poor prognosis and survival rate of only 3-5 months with treatment, the unmet need for novel therapies remains unfilled. For this patient population, especially those with 

According to Mikheeva, when a patient with ATC, immunotherapy is done in order to find the 

 mutation. However, is the mutation cannot be found, the prognosis for these patients can be poor. For patients harboring 

 mutations, targeted therapy may be a possible option to turn to which potentially can increase survival.

 Anaplastic cancer is not very sensitive to a lot of different therapy strategies and standard chemotherapy has a very low effectiveness and not all patients have a 

 mutation. Only about 50% to 70% of our patients have 

 mutations. Of course, we have not enough time to find different approaches for our patients. When we have a patient with anaplastic thyroid cancer, we do the immunochemistry to find the 

 mutation and for 1 day, about 24 hours, we do the data analysis.

In our clinic, we do everything very quickly and if a patient has no 

 mutation and their volume of tumors is very high, we started the standard chemotherapy without targeted therapy because we have such opportunities like another target therapy. That's why if we can't find a 

 mutation, the prognosis of these patient is very poor.

Yuliya Mikheeva, MD, PhD, discusses the many challenges oncologists face in treating patients with anaplastic thyroid cancer harboring BRAF mutations.

Challenges Remain in Treating Anaplastic Thyroid Cancer  

Lori J. Wirth, MD, associate professor of medicine at Harvard Medical School and medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, discusses sequencing therapies for patients with 

 fusion–positive advanced thyroid cancer.

Wirth says she would use the NTRK inhibitor larotrectinib (Vitrakvi) as first-line therapy based on its 75% objective response rate (ORR) in clinical trials. Larotrectinib received a tissue-agnostic FDA approval for solid tumors with an 

 fusion, including in the first line if there is no satisfactory alternative treatment.

However, tumors can develop acquired resistance to NTRK inhibition, so if a patient progressed on larotrectinib, she recommends identifying the mechanism of resistance to find a clinical trial for a second-generation NTRK inhibitor that may prove effective.

Entrectinib (Rozlytrek) is another NTRK inhibitor with the same indication, but it would be less likely to be effective against a tumor that developed resistance to larotrectinib, so it should not be used as second-line therapy, according to Wirth. Another next-line option is a multikinase inhibitor such as lenvatinib (Lenvima), which has shown efficacy in radioiodine-refractory advanced thyroid cancer. However, there are no data on the use of lenvatinib in a patient with acquired resistance to larotrectinib.

 fusion–positive advanced thyroid cancer, generally, I do use larotrectinib in the first line because of the high ORR and very good tolerability. We do know that patients can develop acquired resistance—so they can respond beautifully, but then ultimately begin to develop progression. In patients with acquired resistance, we biopsy the lesion that's growing and do genotyping to see if we can identify the mechanism of acquired resistance. If we have a clinical trial that the patient can enroll on, then we would favor participation in clinical trials because there are second-generation NTRK inhibitors that are being studied now, in the phase 1/phase 2 setting.

If, however, a clinical trial option isn't available, then, in general, I wouldn't turn to another first-generation NTRK inhibitor like entrectinib because we think that the mechanisms of acquired resistance will mean that you can't cross over from larotrectinib to entrectinib and expect any activity with the other drug or vice versa. I think switching over to entrectinib is off the table. But certainly, if a patient is otherwise a candidate for a multikinase inhibitor, I think that that's a reasonable thing to try. I just don't know that we have much data yet on how likely it is that a patient with acquired resistance on larotrectinib would respond to a multikinase inhibitor like lenvatinib, but I'd certainly give lenvatinib a try.

Lori J. Wirth, MD, discusses sequencing therapies for patients with NTRK fusion–positive advanced thyroid cancer.

Sequencing Therapies for Advanced Thyroid Cancer After an NTRK Inhibitor

Vivek Subbiah, MD, an associate professor in the Investigational Cancer Therapeutics department, discusses the adverse events (AEs) that come with the use of kinase inhibitors to treat patients with thyroid cancer.

Vivek Subbiah, MD, discusses the adverse events that come with the use of kinase inhibitors to treat patients with thyroid cancer.