Goldrich: Welcome to STEMPod Leaders, conversations with today's great minds. My name is Nathan Goldrich, the founder of the STEMPod Tutoring Academic Outreach Program. Our guest today is the chair of the Department Of Radiation Oncology at The Stanford School Of Medicine. Her research focuses on translating laboratory findings to the clinic and vice versa in head and neck cancer, specifically in the area of tumor hypoxia and salivary gland stem cells. It is our great privilege to have Dr. Quynh-Thu Le on the program, thank you for being with us, Dr. Le.
Dr. Le: Thank you, Nathan, it's a privilege for me to be joining you and talk about my favorite topic, which is head neck cancer.
Goldrich: So what are some of the common forms of head and neck cancer that you regularly treat?
Dr. Le: So if you think about head and neck cancer, these are the cancer that occur anywhere between the skull base, which is right here [gestures to above right eyebrow] to the clavicle which is right here [gestures]. So the most surface area would be the lining of the aerodigestive tract in that area, so things in the tongue, in the back of the tongue, in the voice box, in the swallowing area of what we call the pharynx, and then obviously the skin in that area. Also, we also treat skin cancer in that area and then other organs that can have cancer in that area, such as the saliva gland. We also have a salivary cancer. We have cancer in your sinuses, in your eyes, etc., and so those are all the areas that we treat.
Goldrich: We know that breast cancer is known to have a strong genetic basis. Are head and neck cancers typically the same way, or do they tend to have larger environmental components?
Dr. Le: Yeah, it tends to be more a larger environmental component. Most of the head and neck cancer that we saw- probably up to about 20 years ago-- were mostly related to tobacco and alcohol use with people [who] used to smoke quite a bit in the past. We still see some of that because you know, the incident of smoking-- even though it's going down-- it's still going up globally, so that's something that we still see globally. A common type of head and neck cancer that we see now is the one that is created by the virus we call the human papillomavirus, so we call it HPV for short. It's the same kind of virus that causes cervical cancer in women and we see them in the head and neck, like in the tonsil and the back of the tongue in men. Rarely we ever get genetic head and neck cancer this [inaudible][2:47] is rare, very rare. There's really not that many genetic causes of head and neck cancer.
Goldrich: How has COVID seemed to affect the rates of head and neck cancer?
Dr. Le: I don't think the COVID has affected the rate of head/neck cancer, but I think we are seeing more advanced cancer being presented to us just because it takes a while for the patient to just be seen when they have symptoms, with the time diagnosis and then not all the medical practices are open at the beginning of the COVID. Now a lot of people are just concerned about getting in to get medical care with the rising rate of COVID, so I think we all are under the impression that we're seeing more advanced cancer when they present to us, we're gathering data to substantiate this. Unfortunately we see it across the board, not just head and neck cancer but other medical issues as well.
Goldrich: What are some of the common symptoms that somebody might have with head and neck cancer?
Dr. Le: So as you know, the symptom is due to the fact that the tumor is in that location. So for example, if it's in the back of the nose and you can present with kind of bleeding to the nose-- or more muffling of the hearing because the nose is connected to the ear in a way-- but with a structure we call eustachian tube- if it's in the back of the throat- then there's more problem with swallowing, but commonly-- because head and neck cancer likes to go to the lymph node very quickly, especially when they are presented inside your throat on the back of your nose. So a lot of these patients will present it with a lymph node in the neck and it's usually around this area [gestures] the angle of the mandible here, that they present. A lot of people will present with just a lymph node without any symptoms and that's how we’ve been doing the work-up, we find out where the tumor arises.
Goldrich: If you have a lymph node in your neck, unless you have no other symptoms, it probably would be pretty hard for patients to identify that they have one of these forms of head and neck cancer, so if a patient does not go into the clinic, are there any other ways that the patient might know that they have it?
Dr. Le: Yes, so the lymph node and then-- we all have lymph nodes in our neck right and it will fluctuate-- being bigger or smaller could be related to, if we have a sore throat, or if we have bad teeth, or we have a toothache, and things like that. The main thing is that the lymph node is getting bigger, it doesn't go away and interestingly enough, the lymph nodes related to cancer tend to be without pain. So if you have a tender lymph node that's swollen when you have a toothache, that's probably more likely related to your toothache, but if you have a growing lymph node that you don't-- that keeps growing and getting bigger and you don't have pain, that tends to be more worrisome. A lot of my patients are men and they tend to find them when they shave.
Goldrich: Head and neck cancer is typically treated with surgery, radiation, and chemotherapy is there a method that you choose all of the time, or does it vary depending on the case and vary depending on the patient?
Dr. Le: Yeah, so we work together very closely as a team for head and neck cancer-- the surgeons, the radiation oncologists, and the medical oncologists, and obviously we need more than that. We need-- speech and swallowing folks will be involved, we need the dentist to be involved, and we need the nutritionist to be involved, but we have a big team managing for head and neck cancer. A lot of the decision is really based on function and obviously we always take patient’s desire into-- because the patient goes through the treatment not any of us right. It’s the patient who has to go through the therapy but we give advice and guidance to the patients based on what we know. I think the top most is really function because I tell my patient we take everything for granted. You and I sitting here, talking, breathing, swallowing, doing things that we don't even quite think twice about it and the cancer and the treatment may affect some of that function substantially. And so to us, and the effect doesn't go away right, it's not a temporary thing. Some of the functional impairment can be permanent and so that's how we decide which way to go. The second thing is, we also decide which way to go depending on the success rate of getting rid of the cancer. We can preserve function but if the treatment doesn't keep the cancer from coming back, then that function will eventually be impaired again, so those really two important aspects that we take into account.
Goldrich: It seems that there is a newer emphasis on immunotherapy as a way of treating cancer. How does that seem to fit into the mix?
Dr. Le: Yeah, so immunotherapy has been shown to be a very good treatment for head and neck cancer once it has spread elsewhere outside of the body-- what we call metastasis-- or once it's come back after the first line of treatment has failed. The first line of treatment is still the standard surgery or radiation plus-- minus chemotherapy, and so there's strong evidence-- multiple randomized studies-- showing the immunotherapy works in those settings very well and it used to be first. If it fails, if you fail chemotherapy when the tumor comes back-- you fail chemotherapy-- then you go to immunotherapy. Now, we know that if the tumor were to come back, immunotherapy in some patients, it's just as good as chemotherapy, or immunotherapy and chemotherapy combination. The question is really-- [is] the bulk of the patient with head and neck cancer still present with curable disease? Between 70% to 80% of these patients do, so the question is how can we move immunotherapy into that setting? And there are a lot of studies-- are ongoing testing that question, whether we can do that. The study doing immunotherapy you know, before surgery. There’s study testing immunotherapy with radiation, or immunotherapy with chemo radiation, etc. We don't know that for probably another year or two, to see whether that is useful.
Goldrich: How does the choice of treatment, on the basis of efficacy, balance out with the patient's desire to maybe reduce cosmetic damage or other variables, because each method of treatment corresponds to a certain number of benefits, but it also corresponds to a certain number of costs?
Dr. Le: Yeah, and so that's called informed consent, right. We sit down with the patient and we talk to them about the benefit-- the data there, what the side effects would be, what the short-term and long-term side effects would be, and how can we balance those two. Part of this, also, we are moving research forward to balance that as well. For example, I told you about these HPV related, oropharynx cancer or the big name for tumor in the back of the tongue and the tonsil. These tumors tend to be very sensitive to radiation and chemotherapy and they do-- the patients do very well and we know with the standard treatment, we cure over 90% of these patients. But we do leave them with a lot of lingering side effects long-term ways, and so the question is, can we actually decrease the treatment intensity or remove some treatment in order to improve the quality of life of patients while balancing-- that we don't affect the survival. We don't want to have less people living because we decrease the treatment, so there's actually several studies-- large studies-- that are leading both nationally and internationally to ask those questions. It's the same idea as lymphoma in the past when in the 50s, if you have a diagnosis, lymphoma-- it's a death diagnosis. Now that you have the diagnosis of lymphoma there are many ways to treat it with less toxicity, so we're reaching that in head and neck cancer.
Goldrich: Let's say that you choose to proceed with a radiation treatment, how do you decide whether to give several small doses over an extended period of time, or one larger dose at a single point?
Dr. Le: Yeah, I think I mentioned to you that head/neck cancer likes to go to the lymph node and once it's gone to the lymph node, our ability to detect the lymph node involvement for a few hundred cancer cells is very poor, even with the modern imaging. And so we-- the head and neck cancer-- unfortunately have to treat big [inaudible][11:58] because most of the patients who presented to us have tumor involved in the neck go into the lymph nodes in the neck. So because of that, we have to balance the side effects-- long-term side effects. So the bigger dose of radiation-- if you can treat in a tiny little area-- the side effect is little, but if you have to treat a big area, the side effect is going to be huge. And so, most of the time nowadays, the head and neck cancer-- we're still treating with a smaller dose each day, over a longer period of time in order to decrease a potential long-term side effects.
Goldrich: Head and neck cancers, they often, as you've already said, they present in areas that are responsible for speaking and responsible for swallowing. Do these processes typically always become impaired when a patient presents with one of these forms of cancer?
Dr. Le: It depends on how big the tumor is and location. For example, if you have a cancer in the front of the tongue-- a lot of your speech, believe it or not, involving the entire tongue not just the front of the tongue, and you can have one nerves-- half the tongue doesn't work. You can learn how to use the other half the tongue for-- to improve your speech and so if a small tumor is in front of the tongue you remove it, the speeches can be pretty-- to the person they may see the difference, but most of us who are talking to the person likely, or cannot, detect the difference. Same thing with the swallowing, if it's in a small area, and most of these are muscle. Muscle can be reworked. The muscle can be exercised, the muscle can be improved, and so if a small tumor-- small area-- that needs to be irradiated or removed, there's processes for us to work with them to help with the swallowing. So yes, we do impact some, but it's not to the point that they cannot swallow or eat. A lot of people actually have really normal function except for the fact, they tell me that they're very dry and every time they take a swallow, they have to take a sip of water.
Goldrich: Much of your research involves looking for ways to restore salivary gland function. How are you going about your research?
Dr. Le: Yeah, so the reason I do that is because probably between 60% to 80% percent of my patients, depending on what area I treat, have dry mouth, and as I mentioned to you, it's hard for them to talk long sentences or they have to take a sip every time they swallow. They spend a fortune on dentist bill because, you know, without saliva you have problem with teeth and you do need teeth for unfortunately, we're not sharks right, we don't replace our teeth! And so that's what we are-- so we found that-- and other groups have found that-- there are stem cells that are in your-- my saliva gland. The younger you have, you have more stem cell. Get older, you have less, but these stem cells if you take out, when you put it in-- and these are mice right, obviously you cannot do it in human-- but you take it out and you put it in a gland that's irradiated, they actually will-- do form new glands, a smaller part of new glands. So then the question is really-- it's hard for us to find these stem cells, like finding the needle in a haystack, because there's only like one stem point, five percent of all our saliva are gland stem cells. So we have to come up with a way to make sure that we preserve them during the radiation, and we stimulate them to regrow and regenerate and so, that's a lot of-- that is learning what processes are involved in preserving the stem cell from radiation damage, what processes stimulate them to grow without obviously causing another cancer to form. So those are really the process that’s going on in the lab and we actually have a drug that we're going to be testing on a patient with soon on this.
Goldrich: You mentioned that you're conducting this research in mice model systems, is the salivary gland system in mice similar enough to humans for us to think that a lot of the data and information that we obtain will carry over?
Dr. Le: Yeah, interestingly enough there's different type of saliva gland and the one that is the submandibular gland, which is the one sit right here [points underneath right jaw], and that's the way the lymph nodes shows up. That's the one that tends to
be-- get an irradiate the most and that's the one that is involved in-- you're sitting there not talking but it keeps your mouth moist and your throat moist, and that's what we call the basil. That gland is-- interestingly enough-- has not changed a lot. It's very similar between mice and rats and pigs and human. When you go to a different type of gland, like the bigger gland up here [gestures in front of right ear] is a little bit different, so yeah.
Goldrich: So taking a step back, what is so interesting to you about radiation oncology?
Dr. Le: What to me radiation oncology is-- I'm more procedurally oriented person and something that I kind of like solving problem and radiation oncology-- the patient present with a problem, I help the patient to address that problem, and solve that problem. But I'm not very good with my hands so I'm not a surgeon, you need to have both, to be both. The second thing is it allowed me really a good connection with the patient. Before head and neck cancer, I spend between six to seven weeks daily with the patient when they go through treatment, and then I spend another five years to make sure that the tumor doesn't come back and then in the future, I correspond with them to make sure it doesn't have side effects. So it's really established a great relationship with the patient, as a patient physician and so that's what I love about it. I’ve also had a lot of physics background and I guess that physics geek in me helped me to understand the radiation principle and the head and neck. In head and neck radiation oncology, you can cure cancer with radiation oncology alone, you don't need surgery or chemotherapy in certain type of cancer.
Goldrich: Do you find that being able to understand conceptually how particle accelerators or how radiation devices work is able to contribute and help you better with patients?
Dr. Le: It helps some but it-- you get a lot of that training during your residencies. You don't have to go into radiation oncology with a strong background in physics. It helps a little bit, but I would say that most training nowaday[s] gives you that strong training in the first place, and if you ever thought about medicine and think about cancer, it's a great field.
Goldrich: What does a typical day look like for you?
Dr. Le: COVID days are little bit different now right. So we usually-- for example today-- the typical day I come in, we have a call of all the chairs and the leaders of Stanford at seven to eight to talk about COVID and how to address testing, vaccine-- anything that's related to COVID. And then I spend quite a bit of time on the calls that manage the COVID issue in the lab and things like that, and I also run a large head and neck cancer consortium for the NCI, and that's to run, to lead large clinical trials. So I spend a lot of time also weekly on some of these call-related stuff, and then I see patients two days a week, and so those two days it's pretty much-- with my time-- to see a patient and then obviously, patient care doesn't stop when you stop seeing them. There are issues that are raised up with patients who have side effects or have symptoms or have things or questions that you need to answer, and so that's how my days are spread out.
Goldrich: Given the fact that the COVID vaccine will-- is not far from being taken by you and I think so many doctors, how do you think that your work schedule will change as a result of having taken the vaccine?
Dr. Le: I think my work schedule will-- well first thing’s first, right now I spend a lot of time on virtual visits for this week, you know. We try to convert as many of-- because our hospital ICU is less than whatever the standard 25% I think we're down in the 20s right now-- so we want to minimize any kind of potential risk to the patient and everybody else. And so a lot of our visits to the patients are virtual visits through video, and then obviously only the patients who come in for treatment, we see them in person. I'm hoping-- and that video visit is great, but it loses that personal touch sometimes and some of the stuff that I do involving procedure, like I have to be able to put a scope in patient's nose to look it out-- so their larynx, so their voice box of their-- the back of their tongue, and so we're holding all that right now. So I'm hoping that all of this can-- back to somewhat normalcy, would be able to hug our patients again, to be able to see our patient again, and do things. But I think we also learn quite a bit about COVID is that, you know, virtual visits are not that bad. That there are positive things about it, but I hope that's there, and then the second thing is travel to meetings. We do a lot of stuff that come out from conversation, interaction, networking, involving-- to be able to talk at lunch, to talk at breaks, and to be able to come up with collaborations. That's not there and so I'm hoping that that will be resuming again when everybody is-- feel safe to travel again.
Goldrich: Earlier on, how did you arrive at a career in radiation oncology?
Dr. Le: I think through, really a mentor. I stumbled on to it just because I trained at UCSF and the rumors-- when I was going through my training-- was this specialty called radiation oncology, where you can learn how to do dictation, you can learn how
to-- [inaudible][22:57] a history and physical exam in preparation for your medicine rotation. And because there's a lot of hands-on interaction with the patient that they allow for medical students, so I went out there and did an elective rotation with the planning to go to medicine and then medical oncology. And then I just fell in love with it after two weeks and one of my mentors, Dr. Karen Fu-- who is also a head neck radiation oncologist and she's retired now-- she's alive but she's retired now-- she really took me under her wings and taught me how to do a head and neck exam and how to interact with patients and with other specialty and I fell in love I guess.
Goldrich: And you mentioned that mentorship played a huge role for you, in general how big of a role do you think mentorship plays in becoming someone in radiation oncology or becoming somebody in a different specialty in medicine?
Dr. Le: I think mentorship is a major role whatever you do in your life even becoming a mother or becoming a father, right? I think most of us don't get the next training for the next step and having somebody there to kind of give you some, you know, points and inputs and you're gonna need to be mentored along your entire life spectrum, right, from going to med[ical] school to residency to become a new faculty member or running your own practice, or, you know, to be even retirement mentorship, some people are afraid to retire because, and so to us, I think it's really important and our department has created a formal mentorship program. We have a really fabulous mentor, Dr. Sarah Donaldson, who has been around for a long time and knows a lot about radiation oncology. She grew up in the time where there's like maybe two or three women in the medical school class together, so she's one of the pioneers and she has really created a great program for all of us to mentor everybody at the full spectrum, and I'm really blessed to have her in our department to do that.
Goldrich: For a student that is interested in going into radiation oncology, what do you think is one of the most important traits that a student can possess?
Dr. Le: I think, loving working with patients. I think a lot of people confuse radiation oncology with radiology. We do a lot of-- we look a lot of imagings because we need to outline the area we want to treat, we need to learn how to see what's tumor and what's normal tissue. We need to know all this stuff but we are really hands-on day-to-day with patients, and so having the ability to connect with the patient and have the, you know, the empathy for the patient because they're going through the hardest part of their life. For many folks when unfortunately, the stigma of cancer is that-- to many people-- they think it’s the death sentence, it’s not! And we need to make sure we work with them and get them through that type of therapy.
Goldrich: What tasks and challenges lay ahead for the upcoming generations and what advice do you have for them?
Dr. Le: One thing is, I think that the upcoming generation is quite smart. The problem is, I see-- and I see my sons-- everybody's looking at-- and sometimes we do that too-- everybody's looking at their ipad, iphone, their smartphone, their computer, and having the conversations-- the ability to hold conversation and interaction and have that social interface is really important for medicine. Also I think I'm hoping that people are going to be more interacting rather than social isolation into the social media, but the second thing is, I think that obviously we'll worry about what the climate change do to health. None of us know, we're hoping that we-- that your generation will have to solve a lot of that, and then how are we going to recover from some of this COVID pandemic. None of us have gone through before but I think you will solve it, you're a very smart generation and then, you will solve it.