Advances in Aggressive Thyroid Cancer Treatment

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research in clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today, I'm happy to be joined by Dr. Joe Scharpf, Director of Head and Neck Endocrine Surgery at the Cleveland Clinic Head and Neck Institute and Dr. Katie Heiden, an endocrine surgeon at the Cleveland Clinic Endocrinology and Metabolism Institute. They're here today to talk to us about advances in the treatment of aggressive thyroid cancers. So welcome Katie and Joe.

Katherine Heiden, MD: Thank you.

Joseph Scharpf, MD: Thanks Dr. Shepard.

Dale Shepard, MD, PhD: So maybe to start out, tell us a little bit about your roles here at Cleveland Clinic. Katie?

Katherine Heiden, MD: So I'm an endocrine surgeon. I primarily focus on thyroid and parathyroid disease. A lot of which is thyroid cancer and less commonly parathyroid cancer. I've been here for two years, prior to that in Chicago for 10 years.

Dale Shepard, MD, PhD: All right. Very good. Joe?

Joseph Scharpf, MD: So I'm in the Otolaryngology Head And Neck Institute. I been here about 24 years. I went away for one year for head and neck training in Iowa for a fellowship, did my residency here. And my role is covering all aspects of head and neck cancer, but I have a particular interest academically and clinically with thyroid in particular advanced thyroid cancers.
Dale Shepard, MD, PhD: Well, excellent. So today we're going to talk about advances in aggressive thyroid cancer. So Joe, maybe you can start us off. Give us a little background about thyroid cancer in general. We have a lot of different people listening in, and so let's give a... Just start broad. What is thyroid cancer? Types of thyroid cancers?

Joseph Scharpf, MD: Sure. You know, the thyroid glands a fascinating organ. Within this one organ, you have some of the most curable cancers of well-differentiated thyroid cancer, primarily papillary follicular going all the way up to probably the deadliest cancer known to humankind an anaplastic cancer. And then in between, some poorly differentiated cancers and then medullary. Thyroid cancer has actually increased dramatically worldwide over the past several decades. And many people feel a little bit of that as a function of diagnostic criteria where ultrasounds, fine needle biopsies are diagnoses some of these cancers at an earlier stage than we used to, but we are seeing more advanced cancers at a higher rate also. And so it's not completely known why that is. And so within thyroid cancer, you have papillary and follicular cancer, very curable, generally treated with surgery, personalized with radioactive iodine as needed based on pathologic findings. And then as you go into some of the more advanced cancers, particularly anaplastic, they may not be operable where we're looking for other types of options, whether they're targeted therapies, radiation and surgery certainly plays a role as well.

Dale Shepard, MD, PhD: All right, excellent. So Katie, we have a multidisciplinary endocrine clinic here to deal with thyroid cancer. Is that true?

Katherine Heiden, MD: Yep. So we have a multidisciplinary clinic where we have endocrinologists, endocrine surgeons, ENT surgeons, all in the same physical space that allows us to facilitate the care of patients in a multidisciplinary way. Often, we bounce ideas off each other, literally in the hallway when we're there together. So it makes it both more convenient for patients. And I think it allows for better and more comprehensive care.

Dale Shepard, MD, PhD: We talked about there's a range of thyroid cancers. Are there particular subtypes of thyroid cancer that are more likely to show up in the clinic?

Katherine Heiden, MD: Yes, I would say that the well-differentiated, which is popular in follicular and
also medullar thyroid cancer patients often will show up in that clinic. Less often, but still occasionally are patients with anaplastic thyroid cancer. They have a different workup and therapeutic algorithm, so they don't always come to that particular clinic.

Dale Shepard, MD, PhD: So Joe, how do most patients end up participating in a multidisciplinary clinic instead of just maybe being referred to a particular provider? Is this sort of a infrastructure we built to... if a person reaches out to see someone they get kind of the group package?

Joseph Scharpf, MD: A lot of times we fortunately will be able to get records from the outside. See what difficult situations certain patients have been facing. Many of these patients may have had recurrent disease from outside treatment. And so it really helps as Dr. Heiden was saying to facilitate their care by moving them into that multidisciplinary clinic, where we can have access for them to our endocrinologists, our other services right then and there on that day, as they may be coming from a distance. Other patients may be in our local community. And it might be more convenient to come to a non multidisciplinary clinic and that's fine. But then in the future, if there's needs for surveillance or other issues, we can move them back into that clinic as well. So it's very free flowing that way.

Dale Shepard, MD, PhD: And I guess if everyone maybe doesn't see everyone in a multidisciplinary clinic, then that's where we get the role of tumor boards. So Katie maybe tells little bit about how we work our tumor boards for thyroid cancers.

Katherine Heiden, MD: So, we have a monthly tumor board, which is attended by surgeons, endocrinologists, radiation oncologists, nuclear medicine physicians, and pathologists, sometimes medical oncologists as well, where we discuss usually the more challenging patients. We discuss all aspects of their history and treatment to date. One of the things that's centered on is the review of the pathology slides. So the slides are actually put on the screen for all of us to review and discuss together. That particular part allows the surgeons and all the providers actually to understand the tumor biology better than just reading a report. And I think that is very helpful to determine both prognosis and treatment plan. So at the end of the tumor board, we have a comprehensive plan for each patient, which is then communicated to the patient after that.

Dale Shepard, MD, PhD: And I think you touched on some of the pathology that seems to be perhaps more important than what some people realize and that's it.... When people get a consult, the path review is really, really important. How often in the cases you guys see with thyroid cancer, do you have a change in diagnosis based on review of the outside path?

Katherine Heiden, MD: Well, one thing we do here is we always review outside slides prior to... Usually prior to even seeing the patient, but certainly prior to doing any surgery or further treatment on them. I don't know if I have a number for how common it is that we would change.

Joseph Scharpf, MD: Yeah, I don't have a number either, but there's definitely times when there's discordance of an outside opinion compared to what we've seen and that can have an impact on patients. For example, there's nuances in even papillary thyroid cancer, there can be a tall cell variant and a more aggressive variant and that may change some of your plan from a surgical perspective or just a treatment plan. So it's nice to have that expertise that we have that might not be as accessible on the outside.

Dale Shepard, MD, PhD: Right.

Katherine Heiden, MD: I would add to that, that a lot of outside reports will be less detailed than the ones here. So they may just say papillary thyroid cancer, and then our pathologist will add these things. So we're not really changing the diagnosis, but adding to it in a really useful way.

Dale Shepard, MD, PhD: And I'm guessing in some ways maybe changing what we're doing from a
treatment standpoint would kind of brings us to the topic at hand is that the new things that are coming around in terms of how we manage these patients. So Joe, maybe as a start, what are some of the newer things that we're doing here at the Cleveland Clinic to manage patients with thyroid cancer?

Joseph Scharpf, MD: So there's been advancements in all fronts, surgical, radiation oncology, when we're looking at more advanced cancers for an organ preservation strategy, for me, the most important is changes in molecular testing, targeted therapies for patients to personalize their care in ways that we weren't able to personalize or even treat in the past. So we're able to have conversations with patients for certain cancers that we weren't having in the past when it comes anaplastic distant metastatic disease. From a surgical standpoint, certainly we have increased safety profile in a lot of our patients with nerve monitoring, perhaps sometimes staging surgeries. If you felt it was safer, preserve both nerves on a particular case. Our radiation technologies improve dramatically using IMRT techniques to decrease surrounding morbidity to tissue in an organ preservation strategy. And then finally, as I mentioned, those real exciting advances are coming from the realm of molecular testing and knowing the molecular profile of these tumors to really personalize treatment for patients.

Dale Shepard, MD, PhD: Excellent. Now you mentioned something in that list that might be worth expanding upon: intraoperative nerve monitoring. What is it? How do we use it? What's the purpose of that?

Joseph Scharpf, MD: So I do on all my patients. I was a little bit of a late adopter, but really have become really it's part of my practice. I'm actually just published a book on a drop of nerve monitoring, and it really gives a safety profile, not necessarily of finding a nerve or protecting a nerve from transecting it, but rather knowing what the functionality is of a nerve. When you're relieving a tumor off of a recurrent nerve, there could be a temporary weakness of that nerve, a nerve proxy, and you never want to be in a situation with both sides being weak and creating a airway emergency, or a tracheotomy need. It gives you a lot of nuanced information for the patients, and helping to make inoperative adjustments as needed.

Dale Shepard, MD, PhD: Interesting. Katie, what do you see as some of the new things that you're using in your practice for thyroid cancer?

Katherine Heiden, MD: So, I'll just expand from what Joe already mentioned, some of those things. So I think the most exciting is in the realm of molecular genetic testing. So we do a lot of next sequence genome testing, and there's several different platforms, commercial platforms. It's also done internally here and at many other institutions. That gives a lot of information, both prognostic information, as well as potential therapeutic targets. So for example, if genome testing on a thyroid cancer may reveal a particular mutation and BRF gene, that will allow us to risk stratify them and potentially depending on the status of their disease, if they end up with recurrent or unresectable disease, maybe a drug target. So, we learn more and more about this as we continue doing this type of work, but I think that's the most exciting. In a similar way, we're starting... You probably know more about this from the anaplastic side, but there's now some studies of PDL one expression in anaplastic thyroid cancer and treatment with PDL one antibodies.

And there's been some promise with that in anaplastic thyroid cancer. So I think that's also very exciting. In particular, within targeted molecular therapies... So we have studies that have looked at multikinase inhibitors in general for patients with advanced thyroid cancer, but specifically patients with advanced thyroid cancer, often the tumors will become de-differentiated and then no longer iodine avid. And that takes away two things. One is the therapeutic availability of radioactive iodine, which is that normal adjuvant treatment. It also takes away the ability to image them very easily, to try to figure out where they're recurring or where they have tumor. So some of these kinase inhibitors have shown the ability to re-differentiate these advanced or aggressive thyroid cancers to make them become iodine avid again, which then allows these patients to be treated with iodine. So I think that's very exciting and hopefully we'll continue to develop that and make that even more useful.

Dale Shepard, MD, PhD: Very good. Now you mentioned something about BRAF mutations. Are we currently doing a trial for patients with a BRAF mutation in a neoadjuvant setting?

Joseph Scharpf, MD: Right. So the BRAF becomes really critical, particularly in aplastic thyroid cancers. So for those patients that are BRAF positive, which is about 40 to 50% of the time and they're inoperable, which is a large majority of our anaplastic patients, they'll undergo treatment with Dabrafenib and Trametinib, and there's a trial they'll be starting here. That I'm one of the surgical leads on for adding Pembro on top of it for treatment. And so we're having conversations with patients where if they're responsive to these treatments, they may become a surgical candidate where they hadn't been before and it is being done in other centers. And it's exciting that we can have this kind of conversation because traditionally anaplastic cancer has generally been about a three to six month survival situation for patients. And now we're seeing patients going well beyond those levels when they're positive for BRAF and have a target.

Dale Shepard, MD, PhD: And having surgical options that were not really possible in the past. So that's good. I guess, from a very practical standpoint, when you look at some other tumor types, the interplay between surgeons, medical oncology, and it makes neoadjuvant treatments difficult sometimes. Is it things like the multidisciplinary clinic probably makes it a little easier? I see far too many people that may have been able to benefit from neoadjuvant treatment, but they've already had their surgery. And so is that one of the areas that, that it is a focus for the multidisciplinary clinic, I guess, to try to figure out who might benefit from those treatments?

Katherine Heiden, MD: Yeah, so anyone with a complex diagnosis would be presented at a tumor board before treatment, and that would be one of the reasons to see if there may be a new adjuvant option and to get input before anything's done.

Joseph Scharpf, MD: I think for many patients, surgery plays the major role for thyroid cancer, but when the morbidity from surgery becomes so extreme and possible loss of organ preservation gives us pause. And we would certainly look for other options. We also have a head and neck tumor board that's independent. So sometimes I'll present patients at both the thyroid tumor board and the head and neck tumor board, where there might be medical oncologist, radiation oncologist, to think through that. Now we're talking about a small subset of patients in the whole scheme of thyroid cancer, but for those patients, it's valuable to have that conversation.

Dale Shepard, MD, PhD: So, Joe, maybe start with you. What are the biggest gaps to moving forward with improving management of thyroid cancer? Are there particular surgical things that just aren't possible and maybe there are the potential to come up with advances that could improve that? Do you think it's more on that medical side? Where do you think the biggest gaps are to improving our ability to treat these patients?

Joseph Scharpf, MD: The biggest gap always has been and continues to be knowing the biologic nature of every tumor before you begin any treatment. As Dr. Heiden was saying, if we can do a molecular testing on a tumor on that FNA sample prior to surgery and see that might have certain mutations, maybe a BRAF in combination with turt mutation, you might be more aggressive about doing a central lymph node dissection or a more extensive surgery than you would've otherwise done. And so, unfortunately we don't always have that information before going into cases. And I think that limits our ability to know how extensive we should be on a particular surgery. But that has always been the gap in that will, I think remain the most important issue, not necessarily diagnostically telling us someone has cancer, but rather how that cancer's going to progress. Because most of these cancers, the patients do wonderful. They really do wonderful from the vast majority of thyroid cancers, but find that subset of patients that aren't going to do wonderful and be able to alter the treatment before it ever begins to change that curve would be very important.

Dale Shepard, MD, PhD: Any other gaps?

Katherine Heiden, MD: Well, to expand on that, to give you an example, as Joe said, the vast majority of patients with well-differentiated thyroid cancer have an excellent prognosis, and many of them don't need any treatment at all. So there are a number of ongoing trials, some of which have been going on for almost 20 years now, on active surveillance for biopsy proven thyroid cancer. And the progression of disease in over five, 10 or 15 years is very low. So it's anywhere between four and maybe up to 10% of those patients ever go on to needing surgery and of those who do, there's no difference in outcome or prognosis by waiting. The problem and the gap is that we don't know how to identify them. And we don't know, more importantly, identify the ones who have aggressive disease. And so we learn as we go. And I think as Joe said, the molecular piece will probably be the most important there as we continue to learn that. But understanding that small subset that have aggressive tumors and need aggressive treatment, we haven't gotten there yet.

Dale Shepard, MD, PhD: How hard is it to convince patients, maybe the provider that referred the patient, to think about surveillance, even though we have long term data that suggests most patients do well? A lot of people hear cancer, they want something done two weeks ago. How hard to sell is active surveillance in this disease?

Joseph Scharpf, MD: We certainly engage patients always in their decisions with it, but I think many come in with the bias not to have active surveillance. And I think they become a little bit concerned that active surveillance hasn't been done in many centers throughout the world. Most of the work has come from a homogenous population in Japan, at the Kuma Hospital. There is a study in New York, that's being done with Dr. Mike Tutle, but not a lot of centers can show their data in such a way that it's been a safe way of following patients and dealing with this cancer.

Dale Shepard, MD, PhD: Katie, what do you think are the biggest educational barriers either for patients or providers in terms of... I mean, I guess what we've heard is that thyroid cancer is a cancer, but most people do pretty well, but everyone still gets sort of concerned when they hear about cancers. What do you think are the biggest educational barriers?

Katherine Heiden, MD: Hearing the word cancer for any patient in almost any type of cancer is very scary. And so we spend a lot of time educating patients about the fact that the vast majority of patients with their tumor have an excellent prognosis and people who are really scared, I'll sometimes bring up the active surveillance just as an example, so that they understand that these tend to be very slow growing, non-aggressive and not life threatening. I don't know if you would add anything to...

Joseph Scharpf, MD: No, I think that's great. I think there's certainly when people hear that word cancer, it is very scary. And I do think there's a tendency for some people to want to be over aggressive about their treatment. In other words, they may want a total thyroidectomy in all cases. Whereas our new ATA guidelines suggest that removing a lobe of the thyroid with the Ismus may be perfectly acceptable treatment for a tumor that's one to four centimeters without adverse features. It has very nice implications for them not having to take hormone. It has very nice implications about not putting certain structures at risk on the other side. But I do think when they hear the word cancer, some patients, many patients, just want an overly aggressive approach to every situation. And I think that educational barrier is something that needs to be overcome.

Katherine Heiden, MD: I agree. And so oftentimes we'll have patients come in who have a previous history of thyroid cancer. And when you look back at their treatment, it was probably overly aggressive with greater than needed extensive surgery. And then oftentimes people will get radioactive iodine when it's really not indicated anymore. And I think that that would be an education gap to providers who do have a tendency still to over-treat, even though we now have a lot of long term data suggesting that we don't need to.

Dale Shepard, MD, PhD: So, it sounds like really both extremes. Some cases, it's relatively indolent and we don't have to do as much as perhaps possible. And for aggressive cases, it sounds like their providers need to know that there are some new things on the horizon that look pretty promising.

Katherine Heiden, MD: And our job ultimately figure out how to identify those two groups.

Dale Shepard, MD, PhD: Yeah. Very good. Well, Dr. Scharpf, Dr. Heiden, I appreciate you joining us today.

Joseph Scharpf, MD: Thank you very much.

Katherine Heiden, MD: Thanks Dr. Shepard.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting Clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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