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BackTable / ENT / Podcast / Transcript #19
Podcast Transcript: Immunotherapy for Head and Neck Cancer
with Dr. Adam Luginbuhl
Dr. Adam Luginbuhl from Thomas Jefferson University Hospitals gives us the 101 on Immunotherapy as a treatment option for Head and Neck Cancer. You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Definition of Head and Neck Cancers
(2) Dr. Luginbuhl’s Philosophy on Cancer Treatment
(3) Introduction to the Field of Cancer Immunotherapy
(4) Pathophysiology and Current Methods of Checkpoint Inhibition
(5) Tumor Microenvironments and Augmentation of the Immune Response
(6) Current Outcomes of Cancer Immunotherapy
(7) Comparing Immunotherapy and Surgery
(8) Predicting Immunotherapy Outcomes Based on Risk Factors
(9) Potential Contraindications and Side Effects of Immunotherapy
(10) The Future of Immunotherapy and Implications for Surgery
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[Dr. Ashley Agan]
Hello, everyone, and welcome to the show. This is the BackTable ENT podcast and our goal here is medical education. We seek to accomplish this goal through conversations with experts in the field of otolaryngology and we hope that you can take this information and apply it to your own practice. I'm Ashley Agan, and I'm a general otolaryngologist practicing in an academic setting at UT Southwestern in Dallas, Texas.
[Dr. Gopi Shah]
And my name is Gopi Shah. I'm a pediatric otolaryngologist practicing at Children's Health in Dallas as well. We're your hosts today and we're so glad that you stopped by to check out our podcast today.
I'm very, very excited for our podcast today. I feel like I'm always excited, but I'm super, especially excited today. Dr Adam Luginbuhl is our guest. Dr. Adam Luginbuhl is an Associate Professor at the Department of Otolaryngology- Head and Neck Surgery at Thomas Jefferson University Hospital in Philadelphia. He's also the Kimmel Cancer Center Director for the squamous cell carcinoma tumor ecology and microenvironment working group. He attained his medical degree from the University of Connecticut School of Medicine and completed his residency in otolaryngology at Thomas Jefferson. He completed his fellowship training in Head and Neck Surgical Oncology at Vanderbilt University in Nashville. He was recently awarded the 2021 Edmund Prince Fowler Thesis Award for basic science by the Triological Society for his animal work in mitigating tissue damage during radiation. He's the principal investigator for three investigator-initiated immune oncology, neoadjuvant trials in head and neck cancer. I'm so very excited to have Adam on the show today. Adam is a close friend of mine. He and I were in the same residency class at Jefferson and his wisdom and kindness carried me for those five years. And not to say this lightly, but truly, genuinely, I survived with Adam. I swam because of Adam. He is here today to talk to us about immunotherapy and head and neck cancer. Welcome to the show, Adam.
[Dr. Adam Luginbuhl]
Thanks, guys. Thrilled to be here.
[Dr. Gopi Shah]
Before we get started, we just wanted you to tell us a little bit about your practice.
[Dr. Adam Luginbuhl]
Yeah, sure. I came back here after training at Vanderbilt. The practice is an inner-city practice at a major institution here in Philadelphia. I predominantly focus on two areas of head and neck surgery. One area is oncologic practice where we treat patients with head and neck cancer, and the second area is reconstruction.
It’s flap reconstruction and our team is pretty much set up so we can tag team all of these cases together. Part of my practice involves robotic surgery, and then in the other part of my life, I mostly spend working with researchers in the laboratory and clinical investigation. At this point of my career, the days I look forward to, are the ones when I get to pursue the questions that plague us in the clinic. I’m trying to bridge the clinical picture in our patients with our researchers that have the wisdom and insight on how to interrogate their tissue and understand the disease process of cancer and its reversal.
(1) Definition of Head and Neck Cancers
[Dr. Gopi Shah]
Today, we're going to talk about cancer immunotherapy. To set the stage for us, can you tell our listeners, when we say “head and neck cancer,” what kinds of cancer are we generally referring to?
[Dr. Adam Luginbuhl]
Sure. Head and neck cancer predominantly has always involved the oral cavity, the larynx, and the oropharynx. It has usually been associated with tobacco and alcohol, the primary drivers of this cancer. I would say that probably in the last 10 to 20 years, we've seen a surge and an increase in oropharyngeal cancer, involving the base of the tongue and the tonsils, that involves human papillomavirus. Additional cancers that we deal with include thyroid gland, parotid glands and skin cancer. Certainly, we see a fair amount of skin cancer that has gotten a bit out of control, and we deal with those that need some radical resections.
The final area that I would comment on is skull-based malignancies. I've spent a significant time working on tumors that come through the skull base and involve that area.
[Dr. Gopi Shah]
When we talk about cancer immunotherapy for head and neck, are we talking about the squamous cell cancers that we traditionally think of? Are you including this entire group of patients when we apply cancer immunotherapy?
[Dr. Adam Luginbuhl]
It's a good question, Gopi. When we think about malignancy as a whole, we're at the infancy of immunotherapy and trying to understand how it affects certain tumor groups. Certainly, in the world I work in, squamous cell carcinoma is the most common, so we have the most knowledge about it. But this doesn't mean that for every rare or random cancer that comes in, we don't think, could this be applied here? Just because it's a rare tumor and we don't see it so frequently, doesn't mean immunotherapy can't be applied. It just means that we just don't have quite the insight yet. Squamous cell carcinoma certainly is the most common thing that we're going to talk about today and it's going to be the one that has the most impact on the greatest population.
(2) Dr. Luginbuhl’s Philosophy on Cancer Treatment
[Dr. Gopi Shah]
When we think about the head and neck cancer patients, we think about laryngeal cancers, as you said: tongue cancers, tongue-based cancers, the types of effects, and how they affect patients in terms of speech, swallowing, and breathing. There are a lot of functional considerations when we take care of these patients. I know it's very dependent on how advanced the cancer is and what type, but can you give our listeners just an overview of your philosophy? What do you think are the most important things, in terms of treatment options like surgery or chemotherapy? What happens when a new patient comes into your clinic?
[Dr. Adam Luginbuhl]
This kind of question comes across a lot of times when students come and ask me about why I chose what I do. And I talk to patients about this. I'm going a roundabout way to answer your question, but I hope it answers, at a more genuine level, what I think about when I see a patient with head and neck cancer.
I tell patients every day, my primary job is really getting people across the river. We all have this fast-flowing river of life, and you just came upon this problem. This is a bad problem, and it's going to be in your face. It's the way you speak, the way you hear, the way you communicate, the way you see yourself in the mirror. All these things are going to be at the forefront of who you are. And we have to navigate and get across the river, treat your cancer, give you the quality of life that you're hoping for, answer all the questions along the way, and carry you on that journey. So, at its very fundamental level, I think that what we do as care providers in the world of cancer, is we shepherd people through these challenges.
[Dr. Gopi Shah]
I think that's a really beautiful way of putting it. I like that analogy. I think for patients who have a new diagnosis, a lot of times it's like, "Okay, now what? You're going to treat it and it's going to be gone." And I think the analogy of having this journey with your doctor is a lot more accurate because, as you say, a lot of these head and neck cancers are affecting the way you communicate with the world, your face, your projection to the world, who you are and how you eat. If you're going to be able to eat, what you're going to be able to eat, and when.
(3) Introduction to the Field of Cancer Immunotherapy
[Dr. Gopi Shah]
I think now is a good time to pivot and specifically get into cancer immunotherapy. You had mentioned that you do different types of surgeries. You briefly mentioned that there is maybe some chemotherapy, radiation, or other options. Specifically, today we're going to look more at cancer immunotherapy, also known as immuno-oncology. Can you set the stage for what that is? What does that even mean?
[Dr. Adam Luginbuhl]
Yeah, sure. Because it's so amazing and so cool, I'll try my best to describe it verbally and paint a picture. Immuno-oncology has revolutionized the way we think about cancer care, across the board: melanoma, lung cancer, kidney cancer, you name it. Immuno-oncology is touching every single aspect of cancer. I think if you ask an average person on the street, "How do we treat cancer?", they'd say surgery, radiation, chemotherapy. There's no doubt in my mind that in five years, it will include immunotherapy at the tip of the tongue of every person. What we're looking at is really the ability to harness a power beyond the drug. The power that allows immunotherapy to have such an effective and profound treatment is, it is you. It is your body’s mechanics killing the cancer. All we're doing with immunotherapy is opening the gates for your body to do what it can do from a biological standpoint.
That being said, if it was easy or straightforward or cured everyone, we certainly wouldn't be sitting here. having this conversation about where we're at and where we're going. But if you look at it this way, the immune system takes care of viruses and bacterias at an alarming rate every day: surveilling, checking, curing, and taking care of your body. For the most part, we are oblivious to it. And in the same fashion, in these same cells (T cells, B cells, APCs, dendritic cells, you name them) are all recognizing the cancer in these patients. And they're hanging out. They make this little deal, "Yo, cancer, over there. I see you, you see me. Let's make an agreement. We'll just live in harmony, we'll hang out, we'll do a little rap song together, but you just keep on doing your thing and I keep doing my thing."
Well, in comes the revolution of immunotherapy, where we put brakes on that. We say, “Don't do that.” And we give permission to these T cells, which are either present or not present, to activate. We give permission to our B cells to start making some memory, and all of a sudden, the cascade starts from there. And now we're no longer focusing on a target, we're focusing on a process.
[Dr. Gopi Shah]
So you're saying that our bodies already have the machinery to identify and attack and eradicate cancer. And immunotherapy is facilitating that process?
[Dr. Adam Luginbuhl]
Yeah, exactly. At a very fundamental level, immunotherapy is giving permission for the cells to do what they do best. But it's a balance, right? There are a lot of cells there that we have to be careful with, right? We could get so excited and say, "Well, why don't we get rid of all the bad cells and keep all the good cells?" Well some of those “bad cells” are actually inhibitory cells to prevent your bodies from going into fulminant autoimmune disorder. So we can't do that. That's kind of what happened in the history of immunotherapy. If you go back to Coley's toxin from 100 years ago or interferon treatment in the 1980s, we see very sick people getting immunotherapy. Their cancers might have gone away, but we destroyed them. That's not acceptable.
(4) Pathophysiology and Current Methods of Checkpoint Inhibition
[Dr. Gopi Shah]
This question is a little bit more targeted to the pathways. We hear the word “checkpoint inhibitors.” Can you get into the pathophysiology? Ashley and I were saying that this is going to be tough because we didn't give Adam a PowerPoint or a white board to show the pathways. But you have a patient that comes into your clinic and they're like, "What are these checkpoint inhibitors?" How do you respond? This has kind of been the buzzword, and what's approved so far, for head and neck cancer treatment.
[Dr. Adam Luginbuhl]
Historically, in CTLA-4 inhibition, the first checkpoint inhibitor approved was ipilimumab, and it was approved for melanoma about five years ago. Forgive me for not knowing exactly when.
Following that, certain cancers fell like dominoes as researchers started to explore and PD-1 became the next thing. Think about it this way. You've got a T cell. The T cell has the ability to attack and kill another cell. And then you have the cancer cell and both cells have this cross linking, which is called PD-1 and PD-L1. That basically is that signal telling the T cell just to hang out. Don't do anything. Don't do anything bad. Let me be me and I'll let you be you.
[Dr. Gopi Shah]
It's like they're co-existing?
[Dr. Adam Luginbuhl]
Yeah.
[Dr. Gopi Shah]
When that's there, they're going to both continue to just…
[Dr. Ashley Agan]
Live their separate best lives?
[Dr. Adam Luginbuhl]
Yeah, live their separate best lives.
We can give a drug like pembrolizumab/Keytruda or nivolumab/Opdivo (those are the two drugs approved for head and neck cancer in 2019) and they block that linkage. Now, the T cell wakes up and it's like, "Holy shnikes, look who's living in my bed. You're not cool, you're out." And then it goes to town and the cascade proceeds. I guess, to focus on your question, that's where we are right now. We have these main players on the stage-- PD-1 inhibition and CTLA-4 inhibition. Those are the main drugs. The ones that are approved for immunotherapy for head and neck are going to be the PD-1s and the PD-L1 is durvalumab made by AstraZeneca. They're all in that big category of checkpoint inhibitors.
I guess the last thing I'll say about checkpoints is there are many of them. There's GITR, there's OX40, there's TIM, there's all kinds of checkpoints that are involved in cancer surveillance. So although we're making it incredibly simple today, I think it is also incredibly amazing how many checkpoints are engaged. And if you turn them all off, what happens? If you turn some of them off, it's like different light switches, if you will.
[Dr. Gopi Shah]
In general, when we hear checkpoint inhibitors, that's the process we think of? There are different types and different names that we're going to hear, but in general, that's the process that is happening?
[Dr. Adam Luginbuhl]
That's right, yes.
(5) Tumor Microenvironments and Augmentation of the Immune Response
[Dr. Gopi Shah]
And then, are there other studies for other parts of the immune system? Like macrophages or other players that are involved?
[Dr. Adam Luginbuhl]
Let's back up and look at how we respond. If we take head and neck cancer as a whole, the CheckMate trials, JAVELIN trials, and all the different trials that came out in the last two years that look at checkpoint inhibition. The studies were done in recurrent metastatic cancer patients, so they're advanced stage, recurrent disease. You're looking at about a 15% cure rate, not great. A bunch of them are responding, but not all the way to cure. It's certainly better than chemo alone, so now it's in the standard of care in the advanced recurrent setting. We're working into the upfront primary currently as we speak. We don't have those trials out yet. But recognize that's not that great of a response so far. You hear excitement about immunotherapy in my voice, but we’re not necessarily knocking this out of the park yet.
So to go back to your question, Gopi, if you think about that as the issue, it's like, "All right, so shoot, we're not doing as well as we thought, we hoped," and that's where the microenvironment comes in. If you look at clinicaltrials.gov, you see all these trials at Jefferson and across the country. We're all saying, "How can we augment the other parts of the immune system to get a response that would be a heck of a lot better than 15% or 20%?" For us, specifically, we've been modifying and working with IDO inhibition. and the PDE5 inhibition. We're working on trying to get those other parts, the natural killer cells, the MDSCs, all of those things that tie into it, out of the way.
[Dr. Gopi Shah]
Can you elaborate on what you mean when you say “tumor microenvironment”? I think when I was preparing for this, that term came up a lot. From what I understand, it's almost like a region where the tumor may be immunosuppressed, as compared to the body as a whole?
[Dr. Adam Luginbuhl]
Yeah, there are so many compartments that when we think about this, the complexity is mind-blowing. You have your systemic compartment, which is what's going on in the bloodstream, which we can measure and tell what's going on in the local environment. And in the local environment, we have an interaction between the tumor and the stroma. And then you have different types of stroma, different phenotypes. When we talk about the microenvironment, we have a tumor and within the tumor, there are some T cells. How did they get there? How did they migrate there? How do we increase the number of T cells that are actually active? This is all about the microenvironment. Are the T cells anergic? Do they actually work? Are they senescent? Are they going to sleep? There's so many different things about T cells.
We can also talk about B cells. One of the things we're currently looking at right now is that some tumors are setting up what's called tertiary lymphoid structure. We know about antigens. The tumor spills out this antigen and the antigen then goes to a B cell. If you can get a B cell to start making antibodies against that antigen, you start to get adaptive immunity. Some of our tumors of the head and neck are forming these small B cell aggregates within the tumor, like little lymph nodes, if you will. They're tertiary. They're not lymph nodes, but they're similar to them and they're spewing out, hopefully, antibodies in the treatment and causing direct tumor kill. These are all the areas of the tumor microenvironment.
[Dr. Gopi Shah]
I've heard another buzzword, “neoantigens.” Are those the cancer antigens that you're talking about, like the use of neoantigens to upregulate the immune response and target the cancer for a patient's cancer?
[Dr. Adam Luginbuhl]
Yeah. Hopefully, we have a paper coming out in Frontiers soon. It's in review, and it talks about the value of using checkpoints before surgery. Let’s say I have a patient with cancer and we remove the cancer, so all the cancer is out, and now I give immunotherapy hoping that it will help. Well, the immune system is going to say, "All right, you just gave me this drug. Where's the tumor? There's not enough volume of tumor here for me to actually mount a response." Even if there's single cells left, it's not enough. You just removed all that cancer.
The thought that we're working with is (and all of our trials are designed this way) while the patient has the tumor, given them a dose of immunotherapy. One dose, maybe two, then operate. Neoadjuvant immunotherapy. What you're doing there is, Gopi, just like you said, you're letting the neoantigens fly around the system and enter the bloodstream. We can find them in the microenvironment. Let those start to make some memory cells, then operate, and then let the immune system do what it knows how to do, which is surveillance. Now, we have this huge surveillance system. Who knows what will happen, but maybe in 5 or 10 years when the cancer wants to creep back up, those B cells are like, "Uh-uh, not again. I've already seen you and you're not allowed here." That's genius.
(6) Current Outcomes of Cancer Immunotherapy
[Dr. Gopi Shah]
When you talk to patients about the checkpoint inhibitors and the drugs that are available, does it help them in terms of survival/cure, or does it buy them more time? Are you talking about months or years? talking years? Is it more symptom relief or palliation?
[Dr. Adam Luginbuhl]
For those listeners who see patients on a regular basis, or those who have a family member with cancer, this might help in some way. One of the beautiful things about this is most replicated and probably first produced in melanoma, and we're seeing the same thing in head and neck. It's this thing called the “long tail.”
Let's talk about chemotherapy first, as a baseline. You give someone chemotherapy A and then you give another patient chemotherapy B. And what we saw with chemotherapy, is that it maybe extended life for 6 or 10 months, but ultimately everybody in the group of really sick patients did not survive. We're not talking about curable people, we're talking about really sick ones.
With immunotherapy, we see a different curve. We see that curve where you not only have 6 or 7 months of progression-free survival and improvement, but you also have this long tail in about 15% to 20% of patients that just survive. We have beautiful pictures of these initial PET scans in people with melanoma everywhere-- bones, lungs, everywhere. And then the next PET scan, nothing. And they go on for 5, 10, 15, 20 years. That's revolutionary. That's new. That's a different expectation.
Now it’s different when we sit with an individual patient. We as doctors often think of population science, right? Unfortunately, the patient thinks about themself as an individual person. One of the hardest things we have to do is translate for a patient, from what our brain is thinking in survival curves to, "What does this mean for this father in front of me? How do I translate that hope and yet the reality that we're not doing great?"
And then the final thing is the side effect profile. Chemotherapy side effect profile, we've proven that in head and neck, Bob Ferris’ paper in New England Journal of Medicine looked at nivolumab demonstrated clearly it gave those with really advanced recurrent disease a better quality of life, even though it only extended life by 7 month. Their quality of life was so much better during that time from getting immunotherapy versus chemotherapy.
(7) Comparing Immunotherapy and Surgery
[Dr. Gopi Shah]
What's tumor board like? When and how is immunotherapy brought up? Let’s say there is a 72-year-old male with a history of laryngeal cancer 20 years ago, who had radiation, and now there's recurrence. We did a laryngectomy and had positive margins. Where does cancer immunotherapy come into play?
[Dr. Adam Luginbuhl]
On one hand there are clear standards of care. FDA-approved, your standard of care is immunotherapy in your recurrent or metastatic cases. Multiple trials have shown that it's better than the extreme trial modality of chemotherapy. Check, we have that. There's no debate there.
I think where the debate comes is in the upfront situation in our trials. Right now we don't have the data to say that it should be used in the upfront setting. We're currently working on it. There are multiple trials running right now for that and, again, we absolutely encourage people to get involved in clinical trials.
But, the discussion comes with (and this is what I personally struggle with) the ethics side of things. A patient in the clinic, like you said, sitting in front of me with a rapidly- growing tumor in the oral cavity. They're in lots of pain. They're not eating and you want to put them on the trial and give them a dose of nivolumab. You want to wait four weeks to see how it responds and if it responds, you give them another dose. If it doesn't respond, you take them to surgery. Man, that's kind of hard to say to a patient, "You're struggling, you're suffering. I want you to hang in there for a hope that this might get a response. And we're going to have to operate either way." And so I would say that that's where I personally will say, "Where are you at right now with your cancer, in terms of how it's affecting your life?"
And if it's really bad, without the evidence yet to show that it's going to move that patient in a meaningful direction, I have to say that I still lean towards getting that patient into surgery sooner, within a week or two. Because you just don't want to see people suffer when you don't have the evidence or data that it's going to make a meaningful difference. That's where I say the tumor board is. We're trying to figure out how best to use our trials with our excitement, but recognize the patient is on the other end of this.
[Dr. Gopi Shah]
You're going to elect to do surgery because that's a known outcome that can make them feel better and prevent suffering. Whereas, there's still some uncertainty with cancer immunotherapy. Is that fair?
[Dr. Adam Luginbuhl]
Yeah. That's such a great way to ask the question because it's so true, right? I feel like we're feeling our way in the dark a little bit here. As a surgeon who's passionately studying this stuff, when the patient walks in the office, we continue as researchers and look at the patient and say, "How can I better help this patient?" And then we translate it into science.
In the last trial we just finished, we used nivolumab plus Cialis. We can talk about why I used Cialis. But we had 50 patients and half my patients had a remarkable response and the other half did not. They didn't progress, but they didn't have a great response. It was about a 50% response. They've all never been treated before, HPV-negative or HPV-positive. I'm looking at this patient and I'm taking them literally with one dose of nivolumab plus Cialis, I take them to the OR four weeks later, and my staging is T0N0.
[Dr. Gopi Shah]
Wow. Do you re-scan them?
[Dr. Adam Luginbuhl]
Yeah, we re-scan them.
We demonstrate that it's gone away, take everything out, do the same surgery. That being said, the next patient I have has no response. And so where do I want to be in 10 years? I want to be in the place where it's like you walk in, I get your blood, I get a sample, I take it to the laboratory and I come back and say, "You don't need to waste your time with immunotherapy. We need to go with conventional surgery, radiation, or chemotherapy,” or I can say, "Hey, you won the lottery here. Yeah, you've got cancer but we have all the markers that point to you being a responder." One of the beautiful things about surgeons being involved in clinical trials is that we have great control over two things. One, the referral base. We have lots of patients coming through. Two, their specimens. Every single specimen we get, we take over to the lab, we sequence it, we run tons of analysis to try to understand that profile of why that patient came out to be a T0N0 after being T2N2b. What happened in four weeks, versus that other patient that didn't budge? And so it's our hope that in 5 or 10 years, we can get to the point where we can be better at predicting. Because not everybody is going to respond.
(8) Predicting Immunotherapy Outcomes Based on Risk Factors
[Dr. Gopi Shah]
Have you all been able to see... are there certain genetic markers, HPV status, or other risk factors that make a patient a better candidate? Do we know these yet? Are HPV- positive patients more responsive to immunotherapy? Are tobacco users more or less responsive? Have any of those things been able to be teased out?
[Dr. Adam Luginbuhl]
Oh, Gopi, I wish we could say at this point that we could. The crazy thing is that your HPV-positive cancers live in immune structures, the tonsils. It's a lymph node and for some strange reason, it's a different phenotype. And all those immune cells there, it doesn't predict whether they're going to... Right now in our trial we have 50% HPV-positive and 50% HPV-negative, and it's a wash. We have some that are responding in both groups. I have complete responders in both groups. So, that's not going to predict for us.
PD-L1 and PD-1 staining is kind of helpful, but not great. It's really poor. What we are finding, at least what we have found in our HPV-negative smokers and drinkers group, is if there is an immune desert in their pre-treatment sample (the sample has no immune cells), they don't respond. They don't generate an immune response.
On the other hand, there are some HPV-negative samples with some T cells, but nothing like the HPV positive group. We find some immune cells, and we're stoked. Those people can generate and produce a significant response. If you're looking for the future and looking for things that will evolve in this field, I think it's the ability to be somewhat predictive and then be prescriptive with who should and who shouldn't get these things.
[Dr. Gopi Shah]
I'm curious if you guys have seen any sort of association with comorbid diseases like diabetes, high blood pressure, or high cholesterol. Are those patients less likely to have an immune system that's going to work for them, in the same way that we see worse outcomes with COVID-19 infection?
[Dr. Adam Luginbuhl]
I don't think so. Let's take a few populations aside, people that have autoimmune disorders already. We're not really giving this to them because we don't want to exacerbate them or cause them greater issues. Although we've talked about the excitement of this, there are some significant side effects in certain groups of patients that can be life-altering in major ways. And so we don't want to always say, "Oh, this is amazing, this is great." We do want to say that, but we also want to say, "We need to be careful." So take aside the group that's at high risk for that. Take aside the group that's already immunodeficient, HIV, and organ transplants. We were having a hard time considering, should we give it to somebody with a liver transplant? We wouldn't have caused rejection. Now I'll leave that to my medical oncology colleagues to articulate that.
But beyond that, we've put it in diabetics. we've put it in people that have obesity. The only thing that we just recently discovered, which was fascinating, is that if you get the therapy and you develop a rash or you develop some small irritation or thyroiditis, you are much more likely to be a responder than if you get nothing. Is that going to be true across the board? I don't know. I don't know if it's generalizable. We're just starting to see these trends. If someone comes in after getting a dose and say, "Yeah, man, I've got the worst rash ever." I'm stoked. That's great. It's a good deal.
(9) Potential Contraindications and Side Effects of Immunotherapy
[Dr. Gopi Shah]
Interesting. You brought up some potential contraindications. Can you talk about side effects and absolute contraindications?
[Dr. Adam Luginbuhl]
Yeah, certainly I think the contraindications are going to be those that have autoimmune disorders already, like lupus, rheumatoid arthritis, even diabetes type one we'd exclude at this point from our trials. I'm going to defer a little bit to our medical oncology colleagues because from their clinical practice, they're going to know some of these details better than I do. I want to be careful in not overstepping my statements here. Real side effects that we're always following are the development of autoimmune disorders.
I have had one patient in a trial develop severe liver failure. And they're rare, but they do happen. When you talk to the patient about putting them on a trial or engaging them, you have to talk about why this is important. In an end-stage, really sick patient with cancer, you're going to accept certain degrees of risk. If a 55-year-old comes in with a T2N1 tonsil cancer, it's hard to make that argument when you're like, "All right, you have a 98% survival rate and we're going to give you a drug that may make your liver fall apart." So we just have to be aware of those ethical considerations as we move into this era.
(10) The Future of Immunotherapy and Implications for Surgery
[Dr. Gopi Shah]
We were in residency together 10 years ago, and I don't recall as much cancer immunotherapy at our tumor board discussions. How has immunotherapy changed the way you practice or think about cancer? Obviously, you've thrown yourself into the research and you genuinely want to understand the disease process. How has it changed your practice or impacted you the most in the last five years?
[Dr. Adam Luginbuhl]
I think I'd go back to the first thing we talked about in this conversation. Early on, when we start as new surgeons, all of us can recognize that we are enthusiastic about treating the disease we've been trained to treat. But as you get more and more into it and you start to see some of the consequences of your treatment, you start to become a little bit horrified that you're doing your best, but you recognize that, "Man, I just removed this person's voice box. Yesterday, I did a hemi facetectomy. What am I doing? Can I make myself obsolete?"
And I think when I see a patient and I look at this treatment and this modality, although it's given by and predominantly treated with medical oncologists, as a surgeon, I want to be at the table to have that conversation with my colleagues about the value of this and where it fits. We don't know yet, but when I look at that patient sitting in front of me, I'd want nothing more than to say, "I have a friend in medical oncology that gets this better and you don't need me." I know that's probably not great for job security, but I hope it's better for these patients.
[Dr. Gopi Shah]
I think at this point in our careers, we've seen and done enough to understand the greater value and the greater good. As a surgeon, you're not the martyr... you know what I mean? That's not sustainable and it's not good for the patient. It's not good care, so I appreciate looking at the entire picture. So, do you imagine a future in which this cancer immunotherapy might be a first-line treatment for patients?
[Dr. Adam Luginbuhl]
I do. I really do. I think that there's going to be a time where it will become first-line, and I also envision that surgery will always be relevant. I don't think it will ever be obsolete. I just think it will develop a more thoughtful approach and there will be another alternative that we can look at. We can weigh different alternatives and look at their value. Going back to surgery, it would be mistaken for me to portray that all surgery is terrible. It isn't. Surgery is very curative, and I believe in the trade. I believe in what we do and patients are very grateful. But I do see a future where we have this new wonderful, powerful tool that can be very useful.
[Dr. Gopi Shah]
I learned so much from you during our time in residency in our conversation today. Thank you so much for joining us. Do you have any other final pearls or last thoughts that you want to leave with our listeners on this topic, or your philosophy on life?
[Dr. Adam Luginbuhl]
Not in particular. I guess I would just express a similar degree for listeners that listen to both of you every week. I have a distinct memory of Gopi, many, many memories. But one in particular I'd like to share, which has to do with her tenacity. For those of you that went through residency before the era of electronics, you remember having to collect films. And Gopi was the second year resident, so she was in charge of films. She had been looking for this film and I had had it in my bag, and in short, she found out I had had it after she had asked me multiple times. When Gopi proceeded to yell at me, she didn't just yell at me standing up. She got up on a chair.
[Dr. Gopi Shah]
I did?
[Dr. Adam Luginbuhl]
Yeah, you stood on a chair in the resident room while I was sitting down to ensure that your emphatic unhappiness with me was made known.
[Dr. Gopi Shah]
I'm just going to pat myself on the back.
[Dr. Adam Luginbuhl]
Yeah, I was like, "Okay, I think she's really pissed."
[Dr. Gopi Shah]
Well, we got the films and the patient was taken care of. I love that. That's awesome.
[Dr. Adam Luginbuhl]
Thank you for letting me hang out with you guys and share my enthusiasm. This is just an awesome time to be in medicine.
[Dr. Gopi Shah]
Thank you for taking the time to talk to us today about a pretty amazing topic. I look forward to seeing how all this plays out over the next several years. For listeners that want to learn more, do you have any recommendations on how to find out more, or any good online resources that you send people to?
[Dr. Adam Luginbuhl]
A great question about resources. If you're in medicine and you treat patients, there are great review articles that you can get on immunotherapy and head and neck. Just put them into your PubMed search and it will generate. Right now I'm sure there's 3 or 4 really strong ones that go over the latest treatments. That'd be the primary place I'd send a medical provider to.
And then if you're a patient listening to this, certainly the main cancer websites-- the NCCN guidelines, the NCI, and the American Head and Neck Society are great websites that have patient-centered material.
Podcast Contributors
Dr. Adam Luginbuhl
Dr. Adam Luginbuhl is an Associate Professor of Otolaryngology Head and Neck Surgery at Thomas Jefferson University.
Dr. Gopi Shah
Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.
Dr. Ashley Agan
Dr. Ashley Agan is a practicing ENT and assistant professor at UT Southwestern Medical Center in Dallas, TX.
Cite This Podcast
BackTable, LLC (Producer). (2021, March 30). Ep. 19 – Immunotherapy for Head and Neck Cancer [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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