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Melanie Cole (Host): Welcome to GW Doc Pod, a peer-to-peer podcast for medical professionals with the George Washington University Hospital. I'm Melanie Cole. And joining me in this panel today to discuss advances in oropharyngeal cancer care is Dr. Arjun Joshi. He's a Professor of Surgery and Head and Neck Cancer and Skull-based Surgery at the George Washington University School of Medicine & Health Sciences and he's affiliated with The George Washington University Hospital; and Dr. Joseph Goodman, he's an Associate Professor of Surgery, Program Director of Otolaryngology Residency at the George Washington University School of Medicine & Health Sciences and he is also affiliated with The George Washington University Hospital.

Gentlemen, thank you so much for being here. This is a really great topic. And Dr. Joshi, I'd like to start with you. What makes oral head and neck cancers unique? How prevalent are they and what have you been seeing in the trends?

Dr. Arjun Joshi: Thanks, Melanie. Thanks for having us today. I think this is going to be a great conversation. So when we talk about head and neck cancers, there are seven different subsites. There's oral cancers, which most people consider as tongue cancers or cancers of the jaw, those are oral cancers. Then you have the oropharyngeal cancers, which are what we are talking about today. And oropharyngeal cancers really are kind of the back of the mouth or the "throat," and that's what people refer to them as. Oropharyngeal cancers are cancers of the tonsil and of the base of tongue. And those are the kinds of cancers that we will be talking about today. You also have voice box cancers or larynx cancers, and there's multiple different subsites of the voice box that we talk about. There's also nasopharyngeal cancers and nasal cancers, those are two separate types of cancers.

So we'll be focusing today on oropharyngeal cancers. And overall, when we're talking about head and neck cancers, we're not talking about a terribly common cancer. This is the ninth most common cancer in the United States. And it comprises about 4% of all cancers in the United States, so roughly there are about 70,000 people nationally that are diagnosed with head and neck cancer in the United States. And so we're looking at a small distinct type of cancer that occurs in a small group of people.

The thing that makes head and neck cancers, in general, very unique is the organs that they affect. Now, when you think about the organs that are integral to function, the tongue is really integral to voicing and speech and swallow and taste. And then, when you're talking about the voice box, the integral nature of it being allowed in terms of generating speech, singing, all of the other things that we do with the voice. These are all critical functions that go on in the head and neck. And so when you have cancers in the head and neck, they can affect these critical functions. And that's what really makes head and neck cancer care a very unique disease entity, because it can really affect so many of those critical structures. What do you think, Dr. Goodman? Do you think that the head and neck cancers that we treat are in some way?

Dr. Joseph Goodman: Yes, I do. I think it's a unique specialty, otolaryngology, head neck surgery, that treats a unique subset of the anatomy and cancers that really affect quality of life and, like Dr. Joshi said, communication, eating, functions that basically can be very disfiguring and distressing for patients who are going through treatment.

Melanie Cole (Host): This is a fascinating topic. And as you've both said, it is certainly a very specialized situation. And due to that and the intricate nature of this type of cancers, Dr. Goodman, I'd like you to speak how medicine has changed in recent years to improve the outcomes. And while these cancers, these oropharyngeal cancers can have devastating effects on appearance and function for the patient, as you just said, and are among some of the most disabling and socially isolating defects with significant impact on a patient's quality of life, I'd like you to speak about some of the evolution of the treatment and what's going on that's really exciting in your field right now.

Dr. Joseph Goodman: So, it's important to recognize that most cancers in the head and neck and in particularly the upper aerodigestive tract have been historically related to smoking, drinking, and behaviors that basically cause insult to the mucosa can lead to those genetic changes that develop into cancers. The good news for oropharyngeal cancer, I guess, it's good news from some respects, is that there's a different entity now at work that's the human papilloma virus. And so, whereas before, maybe 20, 30 years ago, when we talked about oral cancer and oropharyngeal cancer, there wasn't a huge distinction, you know, if it sort of spread from one subset of the tongue posteriorly into the throat pharyngeal wall. But with human papilloma virus-related cancers, they develop within the lymphoid structures of Waldeyer's ring to include the tonsils and the lingual tonsil, which is at the base of tongue. The adenoid pad or the nasopharynx is responsible or is where you find a different type of cancer that's often related to a different virus, Epstein-Barr virus, so there are some analogies. But the point is in terms of treatment for oropharyngeal cancer, the survivability of an HPV-related cancer is significantly better than it used to be and that's for fairly advanced cancers based on size and spread to the lymph nodes.

So, yeah, I want to have Dr. Joshi chime in on some of this, but the treatments that we've been able to offer have excellent oncologic outcomes. And what we've been primarily focused on is trying to decrease the morbidity of treatment. And that's been a huge development, just in the last 10, 15 years.

Dr. Arjun Joshi: I think that serves as a really good intro into the topic. So, we were talking about oropharyngeal cancers, specifically tonsil cancers and base of tongue cancers. And we were talking about the prevalence of the human papillomavirus and its function on creating these sorts of cancers. One of the other things that Dr. Goodman also mentioned that people and patients should know is that these cancers actually behave quite well. So in the majority of these patients, we can expect a general cure for the majority of stage I and stage II patients, which the majority of patients nowadays fall into that stage I, stage II category. And so when you think of a cancer that behaves well, you have a little bit of play in terms of how we can treat these cancers.

So, before, with the types of head neck cancers that we were seeing, these were not related to HPV. These were caused generally by the synergistic effects of smoking and drinking. And so the insult to the lining of the mouth or the throat was significantly greater than what we typically see with human papillomavirus. And so for that reason, those patients tended not to do as well with different strategies. And now, that we have these HPV-related cancers, what we're seeing is we can deescalate. That's the concept that a lot of people are talking about now, deescalation of treatment, for these oropharyngeal cancers.

So when we talk about treatment strategies for oropharyngeal cancers, generally, you can think of three categories of treatments. Now, you could argue there's a fourth one kind of creeping in now and that's immunotherapy, but generally the three forms of treatment that we had to treat any type of head and neck cancer and including oropharyngeal cancers were number, one, surgery; number two, radiation therapy; and number three, chemotherapy. And I would argue that most oncologists, surgical oncologists, radiation oncologists, and medical oncologists would say that, of the three forms of treatment, the one that has the potential for the most lifelong in function is radiation therapy, just in terms of the dry mouth that it can cause, the fibrosis of the throat that the radiation therapy can cause.

And so what we've been doing now, and I'll pass this back on to Dr. Goodman, is trying to figure out combinations of therapies, so combination of surgery or chemo or radiation that can have the least morbidity, the least amount of side effect to that patient while still achieving the same good, solid oncologic outcome that every patient wants to have. And so, over the past 10 to 15 years, we at GW have developed a novel strategy for achieving this result while maintaining that quality of life that's so important to these patients with head and neck cancer. And, Joe, do you want expand on this a little bit more?

Dr. Joseph Goodman: It's important to put it in perspective. So what was considered a stage IV cancer back, say, 10 years ago based on the staging system would've been a relatively moderate sized tumor in the throat, tonsil region, base of tongue, two to four centimeters and spread of multiple lymph nodes in the neck. That would be enough to call that a stage IV cancer. And because of the mortality associated with that being, you know, 40% to 50% over five years, that's before the advent of HPV, we started realizing that not all tumors behave the same. Some seem to have much better prognosis. And then once it was discovered that the human papilloma virus was responsible for certain cancers, especially in patients that had no smoking history or very little drinking history, we started to tease those out. In fact, the staging system changed in 2017, 2018. The eighth edition now breaks off the HPV-related cancers entirely for the oropharynx. And so, we now see the deescalation of the staging system had meant that what was previously a stage IV cancer is maybe a stage II now, and that survivability with adequate treatment is 80 to 90%. So it's a real game-changer, in terms of just what people can expect for outcomes.

Thankfully, there's much less smoking happening in this country. For those who have an HPV-related tumor, but have significant smoking history, generally that's considered about 20-pack years. So that would be a half a pack a day for 40 years or a pack a day for 20 years or two packs a day for 10 years, they can kind of do the math on that. Anything less than 10 would be considered a fairly moderate exposure to tobacco and would probably not significantly affect the prognosis. But the combination of smoking history plus HPV still does have an intermediate range of survivability, so people still need to take some ownership of that.

One of the things that'd be helpful to probably talk about is how we treat these cancers. And that's the most, I would say, exciting thing that we're doing here at GW in particular. And I'd like to bump that back over to Dr. Joshi.

Dr Arjun Joshi: I think one of the really unique things, we were talking about the fact that these HPV-positive cancers, now the majority of them are diagnosed in the stage I, stage II classification. And so the majority of patients are diagnosed as stage I or II patients. And because of that, we've been looking at different types of treatments that can lead to less morbidity. And one of the novel strategies, and you're actually going to see this strategy employed widely across all head and neck cancers, but I think our subset in the oropharynx is pretty unique because we started using chemotherapy in what we call the neoadjuvant setting.

Now, we have to define a few terms here for the general public or for physicians who obviously know about this. So neoadjuvant chemotherapy refers to chemotherapy that's delivered prior to the definitive therapy. And so the definitive therapy in this particular case is surgery. And so what we're using is neoadjuvant chemotherapy to make the surgery less morbid for the patient. Now, what we started doing was on a clinical trial about eight years ago now, it was an IRB-approved clinical trial here at GW, we infused three cycles of chemotherapy for patients who had HPV-positive tumors. We gave them three cycles of chemotherapy, spaced three weeks apart. Now, this is standard chemotherapy that has been around for 50, 60 years for treatment of all sorts of different cancers like gynecologic cancers, lung cancers, specifically cisplatin and taxotere. And so these are two chemotherapy agents that are administered three weeks apart. And the original goal of the treatment was actually to make our operations less morbid for the patient. So imagine if the patient had a 4-centimeter cancer involving the tonsil, if you had to go in and remove that cancer, that patient even 20 years ago would've had what we call a jaw split or a lip split incision. So we would've had to place an incision in the midline of the lip and make an incision through the jaw, and put the jaw back together with plates and screws in order to gain access to the tumor.

Now, another thing that we're going to talk about is also the advent of robotic surgery, which has actually revolutionized the surgical management of oropharyngeal cancers. And we'll touch on that as part of the second piece of this talk. But the point is, initially, we were giving patients chemotherapy to try and make our surgeries more straightforward. And what we found was not only did the surgeries become more straightforward, but in the vast majority of patients with these HPV-positive tonsil and base of tongue cancers, we were finding that they actually had no residual cancers at all remaining in their throats or in their tonsils or base of tongues. Now, that was a pretty remarkable finding. So we initially started this out as, "Let's give patients some chemotherapy. We can make these tumors a little bit more easily resectable with surgery." And then we found out entirely that these tumors were completely gone when we went to remove them transorally. And so based on that clinical finding, we created a clinical trial. And the results of that clinical trial were pretty astounding. I mean, we had the vast majority of patients, now we're talking about originally in that clinical trial, we had a cohort of 25 patients and the vast majority of them, 90 plus percent of them, did not require any radiation therapy following the initial three doses of chemotherapy, which was pretty incredible given the current state of the literature at that time.

And so, at this point now at GW, we've doing this as part of a standard of care. We don't even place patients on clinical trial status anymore when we're discussing treatment options for HPV-positive tumors. And the idea of using neoadjuvant, either chemotherapy or now neoadjuvant immunotherapy as these things are being studied, is a novel strategy. And it's a strategy that's going to be more widely employed in order to try and improve outcomes both surgically and generally oncologically in terms of a survivability standpoint, across a variety of head and neck cancers.

And so this is really a novel strategy. GW was really at the forefront of using this strategy for treatment of oropharyngeal cancers. And it's really interesting because our use of chemotherapy before the definitive treatment isn't new. Centers were trying to use chemotherapy for quite some time before the definitive treatment. So, centers like MD Anderson and Memorial Sloan Kettering, and there was a very well known medical oncologist, David Adelstein, who was looking specifically at using chemotherapy first. But the interesting thing was that the endpoint that they were measuring was totally different. What they were looking at was could giving somebody chemotherapy reduce the risk of distant metastasis now. So giving somebody chemotherapy first, prior to any sort of treatment, so even if your definitive treatment is chemotherapy and radiation versus surgery, could that chemotherapy given in the neoadjuvant setting reduce the chance of distant mets? And that was the question that was studied and that's the reason why neoadjuvant chemotherapy fell out of favor because they found that it really didn't reduce the chance of distant mets. They never actually looked at using neoadjuvant chemotherapy in this setting, in trying to make the surgery less morbid for the patient. And if they had studied that, I think they would've found that in this setting, neoadjuvant chemo made a lot of sense.

I think at this point right now, we've discussed one of the novel strategies that we've been using at GW to try and minimize the use of radiation therapy for head and neck cancers. And I think it's a very promising strategy. It's something that we're constantly trying to refine. Instead of using three cycles, could we potentially use two cycles? That's another question that we could potentially explore down the line. But the use of neoadjuvant systemically delivered drugs is really going to change the management of head and neck cancer over the next 10 to 20 years. And you'll see the strategy being widely employed over the next 10 to 20 years. Now, the agents are going to change. It might be chemotherapy. It might be immunotherapy. It might be combination of the two. But this strategy is going to gain popularity. There's no question.

Dr. Joseph Goodman: I did want to chime in with Dr. Joshi that, being able to do the en bloc resection through the mouth with the da Vinci robot has made all the difference in the world. And so by giving the neoadjuvant chemotherapy and getting a treatment response, we still can adequately assess the margins and be sure based on surgical pathology of what residual disease is there. And then that allows us to tailor postoperative treatment if necessary with radiation or potentially nothing.

And so I think what he was getting to, the complete pathological response seen in that initial study was fascinating, it was 72% complete pathologic response at the primary site and 57% in the lymph nodes. And so many, many of those patients after neoadjuvant cisplatin and Taxotere followed by transoral robotic surgery did not need any other treatment. They did not need radiation at all, although it's still potentially there for salvage if needed down the line. The five-year survival of these patients has been looked at, and it's now disease-free survival 96.1% compared to about 67% in a usual cohort that get chemoradiation. So really fascinating stuff.

Melanie Cole (Host): It certainly is. And thank you both for telling us about how the instrumentation coupled with improved imaging and localization techniques have been used to resect these tumors with minimum damage, I mean, that's really what you're talking about, to the surrounding tissues and the emerging technologies and advancements that have been made as far as minimally invasive technology, TORS, that are allowing surgeons to access those hard to reach areas of the mouth and throat and the neoadjuvant chemotherapy protocols. You've gone over so much today, doctors. I'd like to give you each a chance for a final thought to speak to other physicians here. First of all, Dr. Goodman, I'd like you to answer about the introduction of therapy involving multiple subspecialists, this multidisciplinary approach and given the complexity and with increasingly advanced treatment algorithms are always adding new options your armamentarium of available therapies, how important this is for this group of patients.

Dr. Joseph Goodman: Definitely critical for cancer treatment that's locally advanced. But every patient that we have undergoing this treatment gets presented at our multidisciplinary tumor board. So we've got medical-oncology, radiation-oncology, pathology, radiology, everyone there in attendance to agree or potentially disagree with the plan. But we make sure that these patients are followed by the multidisciplinary team and that shows really excellent outcomes to include supportive care, like speech pathology, which is so important for head and neck cancer, physical therapy, lymphedema therapy, et cetera, cetera.

Melanie Cole (Host): And Dr. Joshi, last word to you. I'd like you to speak about the unique areas that set you apart and why it's important to refer to the specialists at the George Washington University Hospital. And if a physician wants to refer a patient in for oropharyngeal cancer care when is the best time to do that?

Dr. Arjun Joshi: The unique thing about GW is the fact that we look outside the box for different treatment paradigms that might benefit patients. We've been doing this a long time and have a significant experience with head and neck cancer. And we have interesting and novel clinical studies for the treatment of head and neck cancer, which we can involve our patients with. I think if physicians want to refer a patient, it's usually best done at the outset. The truth is that head and neck cancer is complicated. There are a lot of factors that go into deciding treatment options for patients. And I think, just as soon as a patient is diagnosed with a mass in the head and neck, they should be referred over for evaluation.

Melanie Cole (Host): Thank you both so much for joining us today. What a fascinating topic and such an informative podcast. Thank you again for joining us and sharing your incredible expertise in this area. And to refer your patient, you can call 1-888-4GW-DOCS. If you have a question for one of our specialists, please email physicianrelations@gwu.hospital.com.

That concludes this episode of GW Doc Pod, a peer-to-peer podcast for medical professionals with the George Washington University Hospital. I'm Melanie Cole. Thanks so much for tuning in today.

Physicians are independent practitioners who are not employees or agents of the George Washington University Hospital. The hospital shall not be liable for actions or treatment provided by physicians.

Individual results may vary. There are risks associated with any surgical procedure. Speak with your physician about these risks to find out if minimally invasive surgery is right for you.