Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole(Host): Welcome to UAB MedCast. I'm Melanie Cole. And joining me, we have a panel today with Dr. Andrew Fuson. He's an assistant professor and a head and neck surgeon in the Department of Otolaryngology; and Dr. Harishanker Jeyarajan, he's also an assistant professor and head and neck surgeon in the Department of Otolaryngology, and they're both at UAB Medicine. They're here to highlight innovations in the surgical management of oropharyngeal cancer.

Host: Doctors, thank you so much for joining us today. And Dr. Jeyarajan, I'd like to start with you. I'd like you to just kind of set the table for us. Due to the intricate nature of these cancers, how has medicine changed in recent years to improve the outcomes, help patients live longer, better lives? What have been the thought previously and how has that changed in your department?

Dr Harishanker Jeyarajan: So, you know, there's been a significant shift in the way that we treat particularly oropharyngeal cancer when it comes to head and neck mucosal cancers overall. And that's largely been due to the recognition that the human papilloma virus or the HPV virus plays a significant role in the driver of these cancers, particularly in the tonsils and in the tongue base, as opposed to traditional head and neck cancers that are due to smoking and alcohol intake. And what we've noticed is that this kind understanding or appreciation of a change in the underlying pathobiology of the disease kind of came about in the early 2000s. Up until then, we assumed that all oropharyngeal cancers were due to smoking and drinking, and hence had a pretty poor prognosis because they often presented in advanced stage disease. Surgery for these types of diseases at the time was limited very much to traditional open surgical approaches where you would split the lip and split the jaw, cut the tongue to the side to get to the tumor, take the tumor out, and then reconstruct the defect. Oftentimes these surgeries would take all day. They would require patients to be admitted for at least a week, if not more; run a significant risk of perioperative complications, and the patients would still need to undergo radiation treatment and possibly chemotherapy as well. And so because of that, at that time, we shifted towards a non-surgical treatment paradigm for these patients. If someone presented with an oropharyngeal tumor in general, we said, "Listen, you don't want to have surgery. You just want to have chemotherapy and radiation and save surgery if that doesn't work." And so 20 years ago, oropharyngeal cancer had a relatively poor prognosis or we assumed they had a poor prognosis, and we assumed that surgery really played no role in primary treatment.

Fast forward, we understand that in the US, probably over 70% of oropharyngeal tumors now are related to HPV, which means that we know that they do better than their non-HPV-related counterpart. And with the introduction of the surgical robot, we're now able to offer them surgical treatment paradigms with the hope of completely avoiding radiation altogether or possibly decreasing the amount of radiation that these patients get, so decreasing the amount of treatment-related morbidity. And that kind of leads to the second thing.

So firstly, one of the big changes is that surgery has become a standard of care option for patients who present with oropharyngeal cancer now that wasn't there 20 years ago. And secondly is a move towards trying to decrease or what we call deintensify treatment to minimize treatment toxicity while still achieving excellent cure rates. And that's something that we are looking at both from a surgical point of view and from a radiation point of view. And after I'm finished, Dr. Fuson can talk about one of the trials that UAB is actively or trying to get enrolled in, that is actually looking at this. It's a multicenter international collaborative study that he can talk to you about.

But finally, I guess the last thing I wanted to say, the last thing I can think of that we are really trying to focus on now, because we know that these patients overall do incredibly well from a survival point of view, we know that overall survival for the vast majority of these patients is excess of 85-90%. Because of that, there's been a shift in the literature and a shift in all of our focus away from just looking at how can we get these patients to survive towards how can we improve their overall quality of life and try to get them as close as possible to their pre-morbid quality of life. So, we look at voice outcomes, swallow outcomes, and a lot of other functional outcomes and quality of life outcomes to see how can we make sure that whatever we do, whether it's surgery, radiation or combination of both, how can we make sure that not only do we make sure they're alive in 5, 10, 15, 20 years, but actually happy to be there and enjoying their life. And I think those are the three big shifts that I feel we've made in the past 20 years. Andrew, did you want to elaborate on that?

Dr Andrew Fuson: I think what we see really even in the last 20 years, and I'm quite a young physician in the head and neck world, and what I've seen as I've come up through medical school and then training is really an interesting intersection between advances in technology, like surgical robotics and advances in medical science. So in 2003, 2004, we discovered that HPV was a driver for oropharyngeal cancers. And then around that time, we had the advent of companies like Intuitive, really innovating heavily in surgical robotics. And with those two things working together and developing over the last 20 years, that's how we got where we are here today and kind of with an eye on continuing that innovation, continuing that kind of cutting edge care that we're able to offer here at UAB. And particularly with an eye on oropharyngeal cancer, we're looking to get involved in international trials, that are at the forefront that are going to not only prognosticate for people when they, show up with a particular type of cancer, but that are going to improve their outcomes at not only next year, but five years down the line, 10 years down the line, 20 years down the line. And so, we're getting involved with this study out of the UK called PATHOS that is looking to deintensify postoperative treatment in patients diagnosed and treated surgically with oropharyngeal cancer. And that's something that we're very, very excited about. And it's something that we are always thinking about putting our own imprint on here at UAB because we've got just a wonderful group of patients, a world-class group of physicians that deserves to be kind of at the forefront. And so, that's kind of what we are excited about, not just in the last 20 years, but even the last few years.

Host: What an exciting time to be in your field, doctors. And Dr. Fuson, I'd like you to expand just a little bit about the robotics and patient selection for transoral robotic surgery and how endoscopic instrumentation, coupled with improved imaging localization techniques have been used to adequately work with these tumors for minimum damage to surrounding tissues as Dr. Jeyarajan said, because for these patients, it really is about quality of life and that can be so affected by these particular cancers.

Dr Andrew Fuson: Absolutely. So as much as Dr. Jeyarajan and I would both like to think that we could get any tumor out that shows up to our office, really patient selection is quite important. And even small things like height of the mandibles, the shape of the patient's face, those can be vital in determining if these tumors are removable and are safe to remove with a robot. Now, I think the great majority of patients that we see that end up being candidates for robotic removal of their tumor, we take to the operating room and we have a look and we see are these people good candidates, will it benefit them to remove these tumors with the robot? And I think what we find is as we are doing our, 200th, 300th robot case, we're able to predict that much better and really benefit patients much better, fewer trips to the operating room, fewer trips to clinic and people get a really, really nice outcome..

Host: Dr. Jeyarajan, as we're talking about innovations in surgical management for oropharyngeal cancers, it's not only innovation in terms of new technology and devices, but innovation as a philosophical shift from providers working in silos to working together and taking advantage of artificial intelligence and clinical research to really disseminate that data and research quickly. Dr. Fuson mentioned the UK Clinical Trial. Can you speak to how this has really enlarged your field and made it so that you can reach out to other providers really all over the world?

Dr Harishanker Jeyarajan: The PATHOS study is a really interesting example of international collaboration. And as yet, we're still waiting for us to be able to collect the data and to find out exactly what it means. But I do think that it does lend itself towards probably an emergence that happened during COVID. I mean, I think for the last 10 years, a lot of us have traveled internationally, spoken internationally. We've broken down a lot of international barriers and we communicate quite frequently with our partners overseas. But I do think that with COVID, we started utilizing Zoom and other formats to engage in panel discussions, case discussions with colleagues all around the country, and all around the world. And a number of different collaboratives have formed where we kind of share our information, share our data, and share our outcomes in the effort to sort of pursue a global pathway strategy in managing these tumors.

From the point of how we at UAB are innovating, one way that we talked about engaging the PATHOS trial, we at UAB have collaborated with Stanford and Vanderbilt in the targeted fluorescence study that both Andrew and I run here at UAB. Essentially, what we do is we utilize the advanced optics in the intuitive robot, specifically their Firefly system. And essentially, what we do is we take a fluophore, which is basically a chemical compound that absorbs light in one wavelength and then emits it in another. So, we take this compound and bind it to something called panitumumab, which is another chemical compound that we know binds to a receptor that is heavily expressed in head and neck cancers, particularly HPV-related tumors. And what we do is we inject this compound into the patient, and then while they're undergoing their robotic surgery, I can in real time flick between different viewing modes and I can see the cancer cells glow. So essentially at a cellular level, the individual cells that have cancer in them glow. So, I can in real time operate and make sure that I get a microscopically adequate margin around the tumor. Because we know that when it comes to surgery for head and neck cancer at least, the most important thing is to get microscopically clear margins. And I can do that in a very tricky and anatomically complex area by utilizing this technique. And this is a study that is, like I said, it was born out of UAB, Professor Eben Rosenthal, this was his brainchild, him and Professor Jason Warram. And it was developed at UAB and then Dr. Rosenthal sort of took it to Stanford and now he's using it at Vanderbilt. So, three of our centers collaborating to explore this utility both in oropharyngeal cancers and more recently in other cancers as well.

Dr Andrew Fuson: And I think the fluorescence study, similar to PATHOS, it's looking to lessen the morbidity of treatment by assuring us that we've got clear margins without taking too much normal tissue, which is going to be important on that patient, not just in their immediate postoperative period and their immediate postoperative swallowing, but for a long time to come.

Host: Well, that's really what all this is about. And doctors, I'd like to give you each a chance for a final thought. Dr. Fuson, are there any other unique surgical innovations that UAB is employing in this field? Any emerging technologies and advancements that you would like to mention to other providers?

Dr Andrew Fuson: Something that I'm really excited about and something that we have just kind of tried to hit the ground running on is the idea of a blood draw to surveil HPV-related or ary cancers. And what has been discovered in the last, probably the last 20, 25 years is that when you have a tumor, a head and neck tumor, particularly in your body, that tumor is constantly being attacked by your immune system. And tiny parts of the genome of that cancer are circulating throughout your body. And recently, in the last five years, what has come to the forefront is we can track that amount of DNA in your peripheral blood and use it to determine if your cancer has returned or if it's stayed away. And while typically surveillance for head and neck cancer is quite cumbersome, it can be a once a month visit to our office for a year, then once every three months and once every six months, and eventually once a year. And that comes coupled with imaging with flexible exams, which we all as providers like to think are kind of no big deal, but that's not always true for patients. And so, what we're starting to do in our department is to routinely draw what's called circulating tumor HPV DNA to detect for early recurrence of head and neck cancer.

Now, as Dr. Jeyarajan pointed out earlier, recurrences are rarer in HPV-related head and neck cancer, but they still happen. And catching them rarely can be important. It can be of a difference between being able to cure a recurrence with another minimally invasive surgery or radiation or having to consider other options that aren't curative. And so, I think our ability to do this in conjunction with our partners in the industry will hopefully be kind of a game changer in the management of cancer in the long-term.

Host: Well, I certainly imagine that it is, and what you are doing at UAB is really taking medicine to the next level. Dr. Jeyarajan, last word to you. What are the conditions under which you believe patients would benefit most from your experience these procedures with robotics for oropharyngeal cancers? Any other advancements and exciting news that you'd like to share with other providers?

Dr Harishanker Jeyarajan: So for me, I feel anyone who has an oropharyngeal cancer really should be referred for consideration of primary surgical treatment. Now, the ideal patient is someone who has an early stage disease, someone who we can treat and hopefully avoid any radiation on, but there are other patients also who may benefit from transoral robotic surgery with a reduced dose of radiation, for example, people that for whatever reason can't get chemotherapy.

So, I think the easiest thing is, I would love to see any patient who has oropharyngeal cancer, whether it's their first oropharyngeal cancer, whether it's their second or third cancer, whether it's known to be related the HPV virus or not, just so we can have a discussion with the patient and talk about their options and particularly see what kind of benefits robotic resections can provide for them. Our clinics are unique in the sense that we have a speech therapist with us, a specialized head and neck speech therapist with us, who can sit there also and, based on their physical examination, can help me counsel the patient as to how this will affect their overall swallow and overall quality of life.

We are using the robot more and more now for difficult hypopharyngeal and larygeal cancers as well. One of the new innovations that we are exploring with the robot is utilizing the robot with and without the fluorescent imaging system to treat early and intermediate stage of larygeal cancers. These are the cancers that used to be treated with primary radiation and/or open partial laryngeal surgery. And we are finding that in the ones that were not suitable for minimally invasive laser surgery with a new intuitive robot, we're able to get much better access to these tumors and offer them minimally invasive surgery rather than radiation or laryngectomy. And that's something that myself and one of my partners, Bharat Panuganti, who I think has been on your show earlier this month, he and I are working or collaborating on this to try and offer this to some patients.

Host: It's absolutely fascinating. And thank you both so much for joining us and really telling us about some of the exciting things going on in your field. It's really interesting for other providers to hear about all these advancements happening at UAB Medicine. Thank you so much again. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole. Thanks so much for joining us today.