Creating a Guide: Salivary Tumors

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 one and sarcoma programs. Today I'm happy to be joined by Dr. Jessica Geiger, a medical oncologist specializing in head and neck cancers, and now vice chair of the Department of Hematology and Medical Oncology. Dr. Geiger is here today to talk to us about guidelines for managing salivary tumors. So welcome, Jessica.

Jessica Geiger, MD: Thank you. Thank you so much for having me.

Dale Shepard, MD, PhD: And congratulations on the new role as vice chair.

Jessica Geiger, MD: Thank you.

Dale Shepard, MD, PhD: So maybe to start, give us a little idea. What's your role here at Cleveland Clinic?

Jessica Geiger, MD: So like many of my colleagues, we wear sometimes more than one hat. Primarily I am the program leader for the head and neck medical oncology program, which is a very multidisciplinary-centric program just by the nature of treatment and management of head and neck cancers. We rely very heavily on all of our disciplines with head and neck surgery, radiation oncology, and medical oncology, of course. And then as you mentioned, I was recently offered a position as a vice chair for the department, which I am very humbled and grateful, and this is all a new development just over the last week or so. And so I'm excited what opportunities that role can bring and how I can help the department and Taussig Cancer Institute and Cleveland Clinic.

Dale Shepard, MD, PhD: Excellent. So today we're going to talk about salivary tumors and some guidelines that you worked on to help put those together. Let's just take a step back. There's a pretty diverse group that might be listening. Salivary gland tumors. What are they? How rare are they? Tell us a little bit about salivary gland tumors.

Jessica Geiger, MD: Well, so first we need to break it down to the different nomenclature and terminology. So when we talk about salivary gland tumors, we're talking about both benign and cancerous tumors or malignant tumors. And so what's important is thankfully the majority of salivary gland tumors are benign, but this is not what the guideline is about. This is not what I see in my practice. Obviously we see the bad ones, the cancerous ones, the malignant ones. So this guideline is focused on salivary gland malignancies or salivary gland cancers. And they are very rare. So when we think of head and neck cancer in general, a salivary gland cancer accounts for much less than 5% of all the cancers that we see, sometimes even as low as 1% or 2% in a general practice.

Dale Shepard, MD, PhD: So pretty rare.

Jessica Geiger, MD: They are pretty rare. And then not only as a group are they rare. So when we're talking about salivary gland cancers as a group being incredibly rare, then you have to dive in a little bit further because the WHO recognizes actually dozens of different types of salivary gland cancers. And so all of them are exceedingly rare in their own right. Even collectively as a group of salivary gland cancers, very rare.

Dale Shepard, MD, PhD: So how does one think about guidelines for such a rare tumor? So certainly not breast cancer, lung cancer, big trials. How do you go about even starting?

Jessica Geiger, MD: Well, I mean, that was the goal of this group and formulating this guideline was the fact that up to this point, there have been no evidence-based or expert consensus-based guidelines for salivary gland cancer. So this was a first undertaking, a big undertaking. And like other guidelines... you mentioned breast cancer and other more common cancers... this also involved an extensive literature search, trying to find all of the evidence. So a literature search, including over 20 years of looking through systematic reviews, randomized control studies, prospective and retrospective comparative studies. Any kind of clinical trial publications that spanned the year 2000 to 2020 were included. And out of that, about 300 published articles were felt to address the goals of trying to make such a guideline.

But it is difficult. And I would point out that while we strive to be evidence-based, sometimes we don't have the evidence yet. And so these guidelines are very much evidence-based, but it's also rooted in expert panel consensus recommendations as well.

Dale Shepard, MD, PhD: And I guess we'll talk a little bit about guidelines themselves. But when we think about guidelines, a natural question sometimes is guidelines for who. And so given the rarity of these tumors, are most of these treated in a community setting? Are they treated at specialized centers, academic centers? Are the guidelines to provide guidance to people that might be treating the community, or is this more so that you and your colleagues are doing things the same way?

Jessica Geiger, MD: Well, that's the beauty of the guideline is that it should be for both. So in an ideal setting, yes, all of these rare diseases, salivary gland cancers included, would be able to be treated at a large academic or tertiary care center where you have disease-specific experts who even in rare diseases, see this not uncommonly. But in reality, that's not possible for some patients. And so these guidelines can be extrapolated for use not just in head and neck-specific oncology or head and neck surgeons who do this day in and day out, but for community practicing surgeons and physicians as well to be able to very plainly and clearly go back to the different recommendations and the different aims and clinical questions, and make sure that they're going down the right path.

Dale Shepard, MD, PhD: And I guess we'll get to the guidelines here in a second, but I guess one more question about from a patient perspective. Who are the patients that you really think should be here at a tertiary center, at an academic center? There are probably some simpler cases that might be able to be treated more locally, but who's the group that you'd say, "You really got to get that multidisciplinary experience."?

Jessica Geiger, MD: Well, I think anyone who has the diagnosis of a salivary gland cancer. So not just a benign tumor, but a cancer, should if they have the opportunity and the means, at least a consultation with our head and neck surgeons, I think is incredibly valuable only because again, with the different types of salivary gland cancers, they have different histologies. They have different biologic activity. Some are much more aggressive than others. So even in the world of cancer, cancer, as you know, is an umbrella term. Some cancers are much more aggressive than others. And so even though these guidelines are promoted as being salivary gland cancer guidelines, there's little nuances that are very important when it comes to the surgical management of different salivary gland diseases. And so any patient who has been told, "You have a salivary gland tumor. It's cancerous," I would strongly advocate and encourage them to seek the Cleveland Clinic head and neck surgeons, or a large academic center for at the very least a consultation, because the surgical plans can be very different. The work up, the management of them can be very, very different.

Dale Shepard, MD, PhD: In the guidelines, you cover a variety of categories. You talk about diagnosis, preoperative things. You talk about surgery. You talk about radiation and chemotherapy. You talk about all the different categories. Tell us a little bit about that, how you categorize things and what were the things you're trying to encapsulate? Really the journey of the patient, right?

Jessica Geiger, MD: Right. And so the basis of the guideline is to address and aim to answer six main clinical questions. And each of those questions, there may be many, many different recommendations that stem from the single question, but you are right. The six questions sort of encompass the entire patient journey from initial diagnosis and workup evaluation, making the correct diagnosis. And then with that diagnosis, the correct surgical plan. After surgery... by the way, surgery is the mainstay for all of these... every patient should be evaluated for a surgical resection. But after surgery, what is the role of radiation? And that's a specific question. What is the role of systemic therapy or chemotherapy, immunotherapy, all of these other treatments that go all throughout the body that we administer as medical oncologists? That's a separate question in and of itself.

And then after all of that cancer treatment, it's still important. How do we follow patients? What's the appropriate follow-up? What imaging should be obtained and at what intervals of imaging so that we can monitor for hopefully never have a recurrence, but that's important. Some of these patients... Again, there's many different types of salivary gland cancers. Some are more prone to recur than others. And so following them appropriately, that's addressed in one of the clinical questions. And then finally, if this cancer comes back, how do we address a recurrent disease situation? And that is also included in the guidelines.

Dale Shepard, MD, PhD: So among the recommendations, what are some of the examples of things you that you think will make the biggest impact? What do you think as a consensus, as a group, you got together, and you said, "This is how we should be doing this." What do you think are going to make some of the bigger impacts?

Jessica Geiger, MD: The way that patients are diagnosed. So the specific type of biopsy. And I would point out too that the expert panel included in the development of this guideline, multidisciplinary. So not just surgeons, radiation, oncologists, medical oncologists, but also radiologists and pathologists as well. And so first and foremost, we have to make the accurate diagnosis. And so the proper imaging to stage the cancer, the type of biopsy to identify which type of salivary gland tumor or malignancy this is, because if you don't have the right diagnosis going in, then your management can be affected. So that's, I would say one of the main key points that should be derived from this.

Another key point is the extent of surgery. There are a lot of recommendations under that appropriate surgical clinical question, and it addresses again, salivary gland cancers. These can occur in the parotid gland and the submandibular glands, but the facial nerve goes right through the parotid gland. So that has a lot of clinical and functional and quality of life implications if you have to sacrifice the facial nerve. There are certain cancers where that is more important than others because of the way that it tracks along the nerves or the way that it can spread. Again, you don't want to leave any cancer behind, but on the other hand, you don't want to just scoop out anything and everything that you see because the patient could suffer long-term from a functional standpoint because of that. And so the guidelines address, for example, how to and when to preserve the facial nerve, facial nerve monitoring, and other aspects like that.

Dale Shepard, MD, PhD: Certainly, you develop a practice style. We have the way we do it at the Cleveland Clinic. And then you start working with these other groups. What were the biggest surprises? So what were the things that came up as variability in practice style that you found most surprising?

Jessica Geiger, MD: I think management of what to do with the neck. So again, just kind of going back to just the basic nitty-gritty of head and neck cancer. You have your primary tumor, which in this case for the talk of today, it's in a salivary gland. But the risk of these cancers is that they may or may not spread to lymph nodes that are located in the neck. And so how do you manage that? Even on imaging, if you don't see any enlarged lymph nodes that don't... Lymph nodes don't look suspicious for any kind of cancer, but there could still be cancer in them. And so what is the extent of what we call surgical neck dissection or lymph node dissection? How many lymph nodes do you take out? What levels do you remove? Do you remove them, or do you include them in the radiation plan postoperative?

So there were some nuances from institution to institution about that, but I would say that largely with these recommendations, we were at a majority, if not a complete consensus for the vast majority of these recommendations, which is reassuring, because that tells you that there's already amongst larger academic institutions, there's already a sort of standard of care that is then exemplified by these guidelines.

Dale Shepard, MD, PhD: That's great. I guess as you get people together, sort of like-minded and thinking about these things, good opportunity to have people discuss things. Were there research questions that came up through this whole process as you looked at the data that's out there? Was this an opportunity where you could come up with further research ideas and collaborations to say, "Who knew we didn't really know this to the level we thought we should?"

Jessica Geiger, MD: Oh, definitely. I mean, and again, going back to an earlier comment that you made about breast cancer and other cancers having a lot more evidence and data. So this literature search that we did, which, I mean, we essentially looked at everything that has ever been published in those two decades in salivary gland cancers. And out of that, there were only two randomized control trials. So that tells you exactly how rare this is. And again, with a rare disease, it's really difficult to run such large randomized practice-changing trials because the number of patients just doesn't exist. We're not seeing hundreds and thousands of these patients at one institution every year. And so it absolutely highlighted the need that we need to focus not just any clinical trials, but large consortium or cooperative group studies, because that's really the only way that we're going to have enough of these patients, see enough of these patients, and put them on trials to have the numbers to be able to get the evidence that we need for moving the field forward in this. And I think that was very much highlighted by the publication of these guidelines.

Dale Shepard, MD, PhD: And so I guess, kind of a related question, what are the biggest gaps you think that we sort of need to get past in order to improve surgeries and the risk for recurrence and things like that? What do we need to be doing to move the field forward?

Jessica Geiger, MD: Again, I'm biased because I'm speaking as a medical oncologist, but we-

Dale Shepard, MD, PhD: That's okay.

Jessica Geiger, MD: ... we look at all these different histologies or different types of salivary gland cancers, and not only do they behave differently, but a lot of them have unique genomic alterations as well. And so we don't have the results yet, but there was a large... Actually, one of the first randomized control studies and definitely the largest one that was led by Dr. Adelstein here through the RTOG cooperative group, where it looked at after higher risk or higher grade, more aggressive salivary gland cancers were removed surgically. They were randomized to postoperative radiation alone versus radiation plus chemotherapy because right now, there is not enough evidence in all salivary gland cancers to recommend for addition to chemotherapy. And so we don't have the results yet from that, but it did meet accrual a couple of years ago.

And so we don't know what the role of systemic therapy is largely. Is there a role in the curative setting or is it largely focused on the recurrent metastatic, the palliative so-called thing? And I think knowing more, getting more information about the molecular aberrations or the molecular level of each of these different diseases, I think is going to be key because the truth is how we treat adenoid cystic carcinoma, for example, should be and is going to be very different than salivary duct carcinoma or acinic cell carcinoma, or polymorphous adenocarcinoma. I'm just throwing out some of these different histologies just to prove a point of, again traditionally we've been treating them all as one disease, but they're not at all. They're very different diseases and that's a major challenge and hurdle.

Dale Shepard, MD, PhD: And I guess not necessarily within the guidelines, but since we have your insights as a medical oncologist, the role of immunotherapies and genomic-based therapies, how has that moved into salivary cancers?

Jessica Geiger, MD: Yeah. That's really exciting. And you're right. I would just like to say that is not part of the guidelines because it is very, very early on and we really have no data, no evidence to support that. But there are some histologies, the secretory carcinoma that is associated with an NTRK fusion. And so in my practice, for almost any patient with recurrent metastatic salivary gland cancer, I'm offering molecular testing or next-generation sequencing. And I found, not just talking about NTRK fusions, but I found other point mutations for which we have other targeted agents and other diseases that are already approved. So I think it is worth getting this molecular information on these patients because you never know what you're going to find. This is a very heterogeneous group of disease. And we really have very limited chemotherapy options. By and large, chemotherapy doesn't work that well in this disease as a whole. Maybe some histologies more than others, but ultimately it's going to come down to the molecular signature of these diseases and how we're going to be able to treat them.

Dale Shepard, MD, PhD: Wow. Going through 20 years worth of data, certainly a tall order. And so it sounds like a great effort to get guidelines together. Certainly, patients will benefit from that. Their providers will benefit from that. So appreciate your efforts and your insight.

Jessica Geiger, MD: Thank you very much.

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