Hot topics in lung cancer, including screening, immunotherapy, vaping, and more.
Guest: Brendon Stiles, MD, thoracic surgeon at Weill Cornell Medicine and NewYork-Presbyterian Hospital.
Host: John Leonard, MD, world-renowned hematologist and medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital.
Lung Cancer Research and Therapy
Featured Speaker:
Brendon Stiles, MD
Brendon Stiles, MD, is a thoracic surgeon at Weill Cornell Medicine and NewYork-Presbyterian Hospital. Dr. Stiles specializes in treating lung and esophageal cancers, unusual thoracic cancers, and benign chest and upper gastrointestinal diseases. His approach to surgery is individualized to each patient and tumor, and he typically uses minimally invasive, organ-sparing techniques. Dr. Stiles serves as Chair of the Board of Directors of the Lung Cancer Research Foundation, a national non-profit focused on lung cancer research and advocacy, and he is an active social media advocate for lung cancer research and patients. You can follow him on Twitter at @BrendonStilesMD. Transcription:
Lung Cancer Research and Therapy
Dr. John Leonard (Host): Welcome to Weill Cornell Medicine CancerCast: Conversations About New Developments in Medicine, Cancer Care and Research. I’m your host Dr. John Leonard and today we will be discussing the latest in lung cancer research and therapy. My guest today is Dr. Brendon Stiles, a thoracic surgeon at Weill Cornell Medicine New York Presbyterian Hospital. Dr. Stiles specializes in treating lung and esophageal cancers, unusual thoracic cancers and benign chest and upper gastrointestinal diseases. His approach to surgery is individualized to each patient and tumor and he typically uses minimally invasive organ-sparing techniques and we are going to talk about what that means in a minute. Dr. Stiles serves as Chair of the Board of Directors of the Lung Cancer Research Foundation, a national nonprofit focused on lung cancer research and advocacy and he is an active social media advocate for lung cancer research in patients. You can follow him as I do on Twitter at @brendonstilesmd. That’s B-R-E-N-D-O-N-S-T-I-L-E-S-M-D. So, Brendon, it is great to have you here. Thank you for joining us.
Brendon Stiles, MD (Guest): Heh, thanks for having me John.
Host: And I’m really looking forward to this discussion. Lung cancer is obviously an area that is big in the field, from the standpoint of number of patients affected by it as well as all the new developments happening, and I know that you’re attuned to everything that’s going on there. So, I look forward to our discussion.
Dr. Stiles: Great. I agree, it’s an incredible time. I tell my patients not jokingly that there’s never been a better time to have lung cancer and sure you don’t want to have it but if you’re going to have it; lots of amazing things going on in the field right now.
Host: So, tell me a little, how did you get working in this field and you’re a surgeon, but you are also very attuned to the nonsurgical treatments in lung cancer as well. And just from following you, I know you pay close attention to that and are very connected to what’s going on elsewhere. How did you end up working in this area?
Dr. Stiles: Well, starting at the University of Virginia, I really got attracted to the specialty of surgery. I had a lot of really great mentors. I think that’s how a lot of us do what we do. And then I got more and more interested in cancer. I spent some time at Sloane Kettering doing research and then unfortunately, my dad got diagnosed with lung cancer. I was already sort of on the pathway towards thinking about thoracic oncology at that point, but that really galvanized everything for me when I saw what he went through at that time.
Host: How long ago was that?
Dr. Stiles: That was almost 15 years ago.
Host: Well, I’m sure that you take a lot from that experience as you approach patients and think about how you guide your patients through the challenges of dealing with lung cancer.
Dr. Stiles: I definitely do, and I think you see it on both ends, on the diagnosis end but also on the treatment end. He would have been 75 just this week, so I sent something out about that, so it really made me step back and think about all the progress that we’ve made since he passed away and I do think it’s a remarkable time. I never want anybody to have lung cancer, but we just have so many more tools to deal with it now. I think he would be pretty proud of that and that makes me pretty excited.
Host: No, that’s great. It’s great that you can take that forward and certainly in his memory. So, give us for the audience and some people who are listening are probably very familiar with lung cancer, others probably don’t know much about it. give us kind of the 50,000 foot view of the big picture of lung cancer as far as how common is it, it’s one of the more common cancers and the overview that you give as an introduction.
Dr. Stiles: I think that 50,000 foot view is really important. For a very long time, lung cancer was sort of swept away or sort of stigmatized or pushed in the back. People just didn’t really want to talk about it. and often because of its association with smoking and a certain amount of shame associated with it. I’m sure we will talk about later. There is also a sense of hopelessness. Traditionally, we didn’t do well with late-stage lung cancer. A lot of the patients just didn’t do well and passed away unfortunately.
Now, as we are starting to get some good stories and starting to get this idea that anybody can get lung cancer; it’s a lot more in the news. And as you are well aware, a lot of the major advances that have been made the last several years in both targeted therapy and immunotherapy have really been in the lung cancer field.
Why it’s important? It’s the second most common cancer in men. It’s the second most common cancer in women. Prostate is number one in men, breast in women. So, if you put lung cancer together though, it’s probably the most common cancer in many parts of the world. Probably even more important other than the big picture view is that lung cancer takes more lives than any other cancer. There are almost two million deaths a year from lung cancer and in general, we think, and we say, and the literature supports it that lung cancer kills more people than the next three most common cancers combined. So, it’s about one in five lung cancer deaths. So, it really has important implications for patients, for society as a whole, for their family members. It’s a very common cancer. It is going to touch a lot of people’s lives.
Host: How do most patients present? I mean I know some people it’s with an incidental finding, maybe a screening test. Others obviously present with more advanced stage disease and a lot more symptoms. What are the rough proportions there?
Dr. Stiles: That’s a great question John. Lung cancer has not historically done as well with early diagnosis. If you’ve got a tumor growing in your lung; out in the periphery, it is often not going to cause symptoms. Where it causes symptoms is if it has spread to the lymph nodes in the middle of the chest or to other parts of your body and then it’s often too late. Historically, people presented with cough, coughing up blood, fatigue, shortness of breath; and we know that if it gets that far along, it’s often a big problem.
Now, with lung cancer screening, but also with lost of CTs being done on lots of people who walk in the hospital doors; we are finding more and more cancers earlier and we think that that’s improving survival rates.
Host: So, you alluded to the issue of the smoking connection from the standpoint of other cancers, it seems like the second question often comes up is well, did he or she smoke or and obviously, there’s a lot of ancillary baggage to that question and on some level does it matter and also kind of within the community, I’m sure that that is something people struggle with, the focus on that. Give me your take on that as you see.
Dr. Stiles: Yeah that’s a really tough topic to talk about and you definitely have passionate people on both sides. I think without a doubt the most common reason that people get lung cancer is because of previous smoking. We know that there’s a link. That doesn’t mean people deserve to get lung cancer. And it certainly doesn’t mean they should be blamed. Almost every cancer has some sort of choice or decision making or lifestyle issue that has at least contributed to it in some way. But I think what cancer patients don’t want to hear and what lung cancer patients don’t want to hear is that “oh my gosh you have lung cancer, you must have smoked.” Nothing turns them off more than that and really nothing really makes them feel more guilty or feel like they had a role in it.
Nobody deserves lung cancer and I try to avoid asking questions at the get go about smoking. Certainly, most did, but I think most of my patients have quit years and years ago. Now how we talk about that in a big context of cancer and sort of societal issues is really important. I think for the first time in – or over the last 25 years of really seeing cancer rates go down, there was a great report from the American Cancer Society showing a 27% decrease over the last 25 years in cancers. A lot of that, we have to face it has been driven by decreased smoking rates. That’s great.
As we’ve seen that go down though, we see more cancers proportionately never smokers and that’s another important topic to talk about. A lot of our patients advocates, and the patients are out there on targeted therapy are never smokers and so nothing turns them off more than this idea about lung cancer is all about smoking.
Host: So, why are we seeing more lung cancers in never smokers? I mean putting the smoking aside, something else must be happening presumably.
Dr. Stiles: Yeah, another great question. We looked at it in our group of surgical patients just recently here at Cornell and it’s remarkable to see the proportion of never smokers has increased over the years. More recently, in the most recent three years, almost a third of our patients were never smokers which is a pretty amazing number. Now I don’t know, does that mean that more never smokers are getting lung cancer or just that there’s less people smoking so proportionately we are seeing the never smokers come higher? That’s a big question that a lot of people are interested in and trying to answer.
But we know that the things that contribute to lung cancer never smokers, radon exposure is probably the most common so get your homes checked for radon. Probably environmental factors are playing a big role and we are starting to see that a lot in Asia or other countries where there’s a lot of air pollution, that rates are starting to spike a bit there. Certainly, there is probably genetic components that we just don’t understand yet or understand about. That’s probably also this idea that some patients with driver mutations, certain ethnic minorities are more predisposed to those types of cancers, so we know that there must be some genetic component as well.
Research is hopefully going to solve a lot of those things for us. But we are certainly seeing lots of patients who are never smokers.
Host: So, I’m intrigued by the radon question and I’ve read about it, but I haven’t delved into it. So, what is the – what’s the connection there? I mean is it a tight connection? How do you tie that together?
Dr. Stiles: Again, I’m certainly not an expert in the field but actually I’m told that radon, the link of radon to lung cancer was actually made before the link to tobacco smoking and lung cancer. So, it’s been a long-known association and I think it is just inhalation injury and repeated DNA damage that then leads down this pathway to cancer. And then so people, it’s easy to check. Easy to know. So, I think that’s something low hanging fruit to –
Host: So, there’s been a lot over the years, and I know a big focus is in lung cancer screening. Like any screening test, there are complicated issues around that. Obviously, the idea of who to screen, who has got the highest risk and therefore the highest yield, false positives which is clearly a big issue in lung cancer as well as other cancers. Are you going to find tumors that you need to know about that you’re going to change the natural history by finding them early? A lot of things in there. What’s kind of the latest and I know this is a moving target, but what’s kind of the latest or what would you tell someone let’s say with either no risk or some risk as far as how to approach that and think about that?
Dr. Stiles: It’s remarkable. Lung cancer screening really came of age in an era in which there was more skepticism about cancer screening in general and so that’s put a lot more of the pressure on people who advocate for lung cancer screening. But that said, I think lung cancer screening has some of the best data out there for any screening. There was a study called the National Lung Screening Test with over 50,000 patients that showed quite convincingly a 20% reduction in mortality if you get screened.
How those numbers played out and can be twisted around a lot of different ways and so that’s important to know. There’s a second study coming out of Europe that was discussed this year, but we are waiting to see it published called the Nelson Study which showed that the benefit maybe the risk reduction may be even higher in men and even tantalizingly even higher in women. So, 40-60% a different screening than it was for women. So, clearly, I think there’s data out there to support the idea that screening works.
Now how do we get to the implementation is a really important question and what are the bad things from screening is the other important question. And again, you can argue that a little bit of the stigma of lung cancer has kept this in the wings and kept the numbers of patients screened down, this sort of nihilism that eh, they smoked, they are going to get lung cancer, lung cancer is maybe incurable anyways, so why should we screen. But that’s really not the case. Again, we’re talking about studies that show a mortality benefit to patients who are screened. We are talking about moving the diagnosis. So, one of the things you had talked about earlier, how do people present with lung cancer. If you look at all comers, it’s a little bit unusual because over 50% present historically with stage 4 disease. Compare that to prostate and breast where that number is much lower where 80-90% present with local or local regional disease and you can see that you have a problem. We have to find lung cancer earlier.
Screening does that. So, over 60% in most of the big screening studies were found at stage 1. That, we know that we can cure or at least get a jump on. Now back to the bad stuff. So, you used a term false positive. That term always makes me crazy and no offense to you, but this is really what’s been played up and so if you look at some of the things that people have published about lung cancer screening, they’ll say well, three in a thousand fewer people will die from lung cancer with screening, but two in a thousand will have a major complication. And you’ll find a false positive in over 200 in 1000 patients.
A nodule found on lung cancer screening to me is not a false positive. Right, and a lot of people have nodules. We can look out here at everybody walking around on the city streets and if we scan them all, about 20% will have some nodule. To me, it’s only a false positive though if we choose to work it up and go down this pathway where we are worried it’s lung cancer, we are doing invasive studies and taking it out and doing things; then it’s a false positive. Otherwise, it’s just a nodule and we know that most of those are going to be benign. We can follow those with normal CT scans and never have to do anything to those people.
Now the complication rate is also played up that people are going to have all these complications from lung cancer screening, I think is a little bit distorted by the positives. So, if you look at the numbers, they said two in a thousand will have complications from major procedures. Again, this is published by NCI and other groups. But really, that’s all comers. If you take the patients who are found not to have lung cancer, it’s like 6 in 10,000. It’s really the lung cancer patients who go on to get procedures, who go on to get therapy, who go on to get treated, who have maybe complication rates of 10-11% that drive that number up.
This is just a CT scan. It takes less than a minute to do. If we are educated about the nodules and how to follow them, which we are now with great programs called Lung-RADS, there should be very little harm to CT screening.
Host: So, who should get screened?
Dr. Stiles: Yeah, great question. That too, creates a lot of discussion in the advocacy world, right? They want – people want access for everybody to be screened. But I stick strictly to the criteria which the randomized trials shown, and most do and so screening was just approved by CMS in 2015 and it’s really people aged 55-70 and it’s really got to be people with a heavy smoking history. Meaning more than 30-pack-years or a pack a day for 30 years. the more controversial criteria is that they have to have quit within the past 15 years which excludes people who quit many years ago, but I think it’s important for us. Now you can say well what does that get you and if we look at all of our lung cancer patients that I treat surgically, only about 30% would fall into that criteria.
So, some people say we need to screen everybody, and they pound their fists on the table and they say I’m a never smoker, I should be screened. And I understand that. If you are affected by lung cancer, you want to get there. But first we need to do well with the group that we know that it works and that we know that it’s been approved and that we know we have careful clinical trials. And so I think we really need to stick to the screening guidelines and to really work through that to show that we can get rates up and do it safely and then over time, we’ll expand into other groups.
Host: What are the typical options that when you are seeing patients as far as biopsy, surgical procedures. How does that usually go or what sways you one way or another?
Dr. Stiles: There’s lots of options and it’s really hard I think to lay it out on a global basis. Really, there is a lot of individualized care that goes into this. I think the first criteria is seeing that the nodule is there and that it has persisted on multiple scans, you don’t have just a quick trigger finger to any nodule that needs something. Because most are going to be benign. If you see a persistent nodule that looks suspicious our general philosophy is to try to get a biopsy first before doing a therapeutic procedure. I think that’s safe and that sort of decreases this idea of harming patients who don’t have lung cancer. And there are lots of ways to get biopsies, CT-guided, bronchoscopic. Sometimes we will take a patient for a surgical biopsy if we are very suspicious. But I think for people out there at other places, just do what your place does best. If they are better at CT biopsy, do that; if they are better at bronchoscopic biopsy, do that. And often getting more information first, PET scans or other sort of data points that you can use to help determine the likelihood that it is a cancer.
Host: What is the typical scenario?
Dr. Stiles: Well here is the problem John it really falls on the responsibility of the primary care physicians and I think they are the group that has least embraced lung cancer screening. And that may be historically based on biases and maybe on the fact that these are incredibly busy people who have a lot of things going on. One of the interesting requirements of lung cancer screening is that it was only approved with a shared decision making visit. It’s a little bit unique from cancers in that you have to have this discussion about it.
That’s a little intimidating for primary care physicians or others who aren’t thinking about lung cancer all the time and may not be up to speed on the data about screening. A lot of screening programs have tried to make that easier by saying we’ll have that decision making conversation if you as a primary care physician refer the patient to us for screening.
Ultimately, it’s going to come down to the primary care physicians to recognize and identify which patients meet the screening criteria and then to get them into screening systems.
Host: So, on the surgical side, what are kind of my time in the operating room goes back a couple of decades in medical school. What I recall the most is big operations, chest tubes, pain because people have pain every time, they take a breath. Clearly, the field has moved, and I know from my own patients that we shared, into many more cases being manage through minimally invasive and newer kind of techniques. Can you give us kind of a quick overview.
Dr. Stiles: Yeah, it’s really fun to be a lung cancer surgeon now. We have a lot of great tools as our disposal and when I give the lecture to the med students, I always show the pictures of the guy almost getting cut in half and having his whole lung taken out to the guy getting partially cut in half to the little incisions to even the surgical robot. And it really has evolved over time. I think at Cornell, over 90% of our lung cancer operations are minimally invasive with two or three little small incisions which we think is pretty good and pretty remarkable.
We think that really helps patients get over the surgery quicker. We think we can still do the same cancer operation through those small incisions. We’ve shown that it leads to less complications over time. We are increasingly trying to refine that and to – whether it’s with the robotic system, whether it’s with other minimally invasive platforms and to do better smaller incisions that are less painful. And increasingly, we are starting to look at the idea of not just little incisions, but can we take out less lung. Can we do lung-sparing surgery to give these patients who are going to be hopefully they are going to need their lungs for the rest of their life, so we want to save as much as we can in the confines of still doing a good cancer operation.
Host: So, from the standpoint of taking care of these patients, it seems like a multidisciplinary team is pretty important. What’s kind of the state-of-the-art from the standpoint of involving the radiation oncologists, the medical oncologists in different cases? Kind of how does that typically work and the advantage of a center like here that has the team that can kind of all put their heads together fairly efficiently.
Dr. Stiles: I think that’s critical and we really emphasize multidisciplinary care and I think a lot of people out there in the know about lung cancer really do, because it is such a fast moving field, particularly as you get to the more advanced stages and how you are going to do that may be different at three different places and so you really do need a lot of input and it’s pretty nuanced per the patient.
For early stage disease, the radiologist touches the patient, the pulmonologist touches the patient, the surgeon touches the patient, for some patients radiation therapy, stereotactic radiation is an option and so we try to discuss all these cases at our multidisciplinary tumor board and really tailor the treatment to that patient who is right in front of us. Granted, that’s hard to convey who that person is to everybody sitting in the room sometimes. But I think that’s a really important part of what we do.
As you go up stages to stage 2, stage 3 where you might have potential different treatment paths, sometimes chemo first, sometimes immunotherapy first, sometimes surgery first; it becomes even more important to layer in all those opinions and to make sure that we are doing what’s right for our patients.
Host: So, immunotherapy is a big buzz word and you just alluded to using that before surgery in some cases; why is immunotherapy so relevant to lung cancer? I mean there are certain other cancers, obviously, but why lung cancer in particular?
Dr. Stiles: Well it’s been amazing. I mean it has really revolutionized lung cancer and if you look just back from 2015 to now, who gets immunotherapy is amazing. We think lung cancer is kind of a smart cancer, people have described it. There is dumb cancers and smart cancers. The dumb ones are really driven by one or two mutations and don’t have a high mutational complexity. Lung cancer is pretty smart though, right, it’s got a high burden of mutations. It’s got ways to get around other therapies. And while that’s bad for standard therapy, chemotherapy and targeted therapy, may be it’s good for immunotherapy because it means they’ve got a lot of things going on. The body recognizes that this shouldn’t be happening, they say it’s foreign and so it can harness it’s immune system to help fight it.
Immunotherapy really can’t be a stage 4 lung cancer patient unless you have a specific targeted mutation and not get immunotherapy these days. If you have over 50% expression of a certain protein, you might just get immunotherapy alone. Which is pretty remarkable to think about. You must be a stage 4 lung cancer patient and not get any chemotherapy now and quite a few don’t.
Even if you don’t have high expression of that protein, immunotherapy often comes into the frontline for a current stage 4 lung cancer patient.
Host: So, a big buzz word is precision medicine and precision therapy and immunotherapy is a part of that. I know that going back years, someone would have surgery or get a biopsy and it would be histology. You just say it’s small cell, non-small cell adeno, squamous, etc. Now there’s a whole panel of things that get checked and how would you say that’s kind of impacted things and from this state-of-the-art of what a patient should have done when they are diagnosed these days?
Dr. Stiles: Yeah, another really remarkable thing and again, the thing that I show the med students every time I talk about this is just how we have evolved, and I show a chart, when I started giving the lecture, that talks about treatment of stage 4 and it just said chemotherapy and consider targeted therapy. And then I show this chart that somebody actually made and sent to me on Twitter that’s got all these crazy pathways depending on what you have here, there, wherever, everywhere and so many different options which is just incredible to think about.
For us, the really – lung cancer is not just one cancer like you say. It’s really a host of cancers. Some driven by driver mutations like EGFR or ALK or ROS1. Even the ones that don’t have those, then we look for expression of an immune protein, PDL1 to sort of segregate how they are going to be treated. And so there’s multiple different pathways.
And even for us in the earlier stage disease and in resectable disease; these things are starting to become important. It’s not just as you said, small cell and non-small cell. Now it’s adenocarcinoma, different subtypes of adenocarcinoma are some of those more amenable to lung sparing surgery than other ones. Do we need to take out the whole lobe? Can we save some? And so these things that – it’s really pathology, right? Pathology matters. And the tissue is the issue. It really tells us how we are going to treat lung cancer and so I think any center where you are, should put a priority on having an excellent pathology service in checking all these mutations and histologic subtypes in lung cancer.
Host: So, are a large percentage of patients getting some sort of systemic treatment before surgery?
Dr. Stiles: Another good question. And really Nasser Altorki who is my boss has really been a leader in this idea. This idea of window of opportunity trials. So, can we give a drug into the patients before we take it out to number one, improve their survival, number two to improve our ability to resect those patients. There’s been a couple of trials with targeted therapy to try that. There’s another one going to be rolling out again for that, a national trial.
Here at Cornell right now, we are interested in giving immunotherapy preceding surgical resection and that’s not novel. There are lots of places excited about that too, with the immunotherapy wave. But we have a great trial that where we combine it with small doses of radiation to try to immune prime the patients. And we are seeing some remarkable responses. That’s mostly for late stage 1, stage 2 and stage 3. For early stage 1 which is still most of our surgical patients, they are still going straight to surgery. But for that in between stage 1 and stage 4, that’s really where we think we can move the needle with some of these trials before surgery.
Host: So, I know a big part of what you do is research in this area. What are some of the things you’re working on and what do you think is also big in the field that people ought to keep an eye on?
Dr. Stiles: Well everybody is interested in the immune system, how that interacts with everything else and so, that’s our lab is really focused on that and that’s again led by Nasser Altorki and Tim McGraw, we have partnered with a lot of great scientists. We really think that studying patient material and then sort of looking in the lab and then bringing it back to the patients is the way that all this should work and so we put a big emphasis on that. We are trying to understand the immune microenvironment in these cancers and trying to understand why one may respond to immunotherapy and why another won’t, how we can boost one up with radiation therapy to make it more immune responsive. I’m particularly focused on a protein that I think may sort of serve as a check point inhibitor kind of like the more classic check point inhibitors PDL1 and the role of that in immunotherapy.
Lots of exciting things going on there. Our group as surgeons has always been interested in biomarkers and again how do we segregate patients but how do we go back to that screening idea and if we have a patient who has a CT scan with a nodule, can we figure out more about it than that? Is there some blood marker we can find? Is there something else about the patient that will tell us this is more likelihood of cancer?
Those are big things in the field and then resistance to targeted therapy. So, one of the things we haven’t talked about as much and that’s really changed the face of lung cancer is EGFR based therapy, ALK based therapy, ROS 1 based therapy. These patients are doing so well now. There was actually an amazing report from the University of Colorado recently that showed almost a seven year survival with stage 4 ALK rearranged lung cancer. Amazing when you think about the standard survival for a stage 4 patient is less than a year. But the patients are doing so well, they eventually develop resistance to these drugs and so finding the second way around or the next generation drug that works for that or finding ways to combine with other therapy like immunotherapy or chemotherapy is a big focus of research right now in the lung cancer space.
Host: And what about prevention? From the standpoint I know a big risk factor of getting a lung cancer of having had one before and I know one of the things you think about in your patients is when they’ve been cured of one lung cancer, avoiding another one and I’m going to ask you also about totally unrelated but connected a little bit this whole issue of E-cigarettes and changing all of that. Because I know nothing about that. But I know it’s getting a lot of attention from the FDA. So, not to come back to smoking, but those two points.
Dr. Stiles: Well the E-cigarettes and vaping is a great issue. I’ll come back to that in a second. I think prevention is largely by stopping tobacco products. And I think that we sort of – I always say the golden moment to stop smoking for patients who still do it is when they are in the hospital after they have had surgery and we really believe that in screening programs there’s always or there’s also evidence that smoking cessation programs, they work well there. And then it’s just other things. It’s hard to put a pinpoint on nutrition, air quality, exercise probably have some role.
Back to E-cigarettes and vaping, I have spent a lot of time thinking about that lately and on the – it’s an amazingly polarizing thing. Like if you talk about some of the things that I have put on social media that’s I’ve gotten the most negative comments on, it’s been comments about vaping. I think that first of all, they are potentially a great adjunct for patients who are trying to quit cigarettes. And there was just a New England Journal paper that showed that double the rate of quitting tobacco at one year. The problem though is that really that there has been this onslaught of young people using these E-cigarettes and vaping and this idea of flavored vaping and all these things and also from the New England Journal showing that an eight to ten percent increase per year in vaping in teens. That means over one million new vapers a year. It means almost 20% of 12th graders are using E-cigarettes.
That has incredible implications and we were fooled once by cigarettes. It’s an amazing story about the denial of the link of tobacco with lung cancer. Certainly, E-cigarettes are safer, but there’s also some suggestions that they are not totally safe. And I think whether we want to introduce teens to that or introduce them to nicotine which is potentially a gateway to regular cigarettes; that’s an issue that we have got to pay a lot of attention to.
Host: So, I want to wrap up with just your thoughts on your advocacy, because I know you’re involved with the Lung Cancer Research Foundation, you are out on social media. Advocacy can be a very powerful thing. I’m not sure that the Lung Cancer community has been as strong as perhaps others given the number of people affected by it. But clearly, you put a lot of time and effort into it so you think – and I agree, I do the same thing in the lymphoma community; what advice do you have about patients, family members, potential advocates out there as to the value of these sorts of efforts and how would you suggest that they get engaged one way or another?
Dr. Stiles: Well first of all, it’s an understatement to say you do the same. You’re amazing. So, I have seen your career and what you do for advocacy has really been sort of inspirational to me. When I went to the Lymphoma Foundation Research and saw them honor you, it really is amazed and remarkable.
I think all physicians should be advocates for the diseases that they treat if they really believe in it and really believe in the patients there. It’s tough though for a disease like lung cancer and you have to approach patients. Not everybody wants to be an advocate or put themselves out there. But I think that is still historically based on some of the stigma associate with it.
I love talking to patients. I love for patients to share their story whether it’s good stories or sometimes bad stories. But we try to get them involved with talking to our medical students. I was amazed this year, they gave me an extra half an hour to talk to the med students and then I realized it was just they wanted to hear the patients more and not me. And that rings true though. People want to hear patient’s stories. People want to understand how if affects their lives. They want to know about how lung cancer can affect anybody. So, there’s increasingly on social media and things like this, there’s more of a push in lung cancer for people to share their stories. And I think that’s critical for the disease. It’s critical for making a link for research in patient stories.
Host: Great, so before we wrap up any other messages or take home messages beyond that, for patients that you would suggest as they think about dealing with a lung cancer?
Dr. Stiles: Well I think share your story. I think get lots of second opinions. I think it’s a complicated disease and like a lot of the cancers that we treat here at Cornell, there may be some benefit into seeing a center of excellence or seeing experts in the field. Don’t be alarmed if they say different things and again don’t be afraid to go get treated in your community. That’s just as important too. But I think don’t miss the opportunity to make sure that you are getting the right treatment because like you said John, lung cancer is not just small cell and non-small cell, there’s so many nuances now and the field is moving so fast, it’s hard for people to keep up with. So, be your own advocate for your disease. Ask for second opinions. Ask what’s happening out there in the lung cancer world and share your stories most importantly.
Host: Great. Well this has been a fabulous discussion. Thank you for joining us and I have a feeling we’ll have you back again before too long to talk about all the progress. So, I want to thank our audience for joining us. And I want to encourage you to download, subscribe, rate and review Cancer Cast on Apple podcasts Google Play Music or online at www.weillcornell.org. We also encourage you to write to us at cancercast@med.cornell.edu with questions, comments and topics you’d like to see us cover more in depth in the future. That’s it for Cancer Cast: Conversations About New Developments in Medicine, Cancer Care and Research. I’m Dr. John Leonard. Thanks for tuning in.
Lung Cancer Research and Therapy
Dr. John Leonard (Host): Welcome to Weill Cornell Medicine CancerCast: Conversations About New Developments in Medicine, Cancer Care and Research. I’m your host Dr. John Leonard and today we will be discussing the latest in lung cancer research and therapy. My guest today is Dr. Brendon Stiles, a thoracic surgeon at Weill Cornell Medicine New York Presbyterian Hospital. Dr. Stiles specializes in treating lung and esophageal cancers, unusual thoracic cancers and benign chest and upper gastrointestinal diseases. His approach to surgery is individualized to each patient and tumor and he typically uses minimally invasive organ-sparing techniques and we are going to talk about what that means in a minute. Dr. Stiles serves as Chair of the Board of Directors of the Lung Cancer Research Foundation, a national nonprofit focused on lung cancer research and advocacy and he is an active social media advocate for lung cancer research in patients. You can follow him as I do on Twitter at @brendonstilesmd. That’s B-R-E-N-D-O-N-S-T-I-L-E-S-M-D. So, Brendon, it is great to have you here. Thank you for joining us.
Brendon Stiles, MD (Guest): Heh, thanks for having me John.
Host: And I’m really looking forward to this discussion. Lung cancer is obviously an area that is big in the field, from the standpoint of number of patients affected by it as well as all the new developments happening, and I know that you’re attuned to everything that’s going on there. So, I look forward to our discussion.
Dr. Stiles: Great. I agree, it’s an incredible time. I tell my patients not jokingly that there’s never been a better time to have lung cancer and sure you don’t want to have it but if you’re going to have it; lots of amazing things going on in the field right now.
Host: So, tell me a little, how did you get working in this field and you’re a surgeon, but you are also very attuned to the nonsurgical treatments in lung cancer as well. And just from following you, I know you pay close attention to that and are very connected to what’s going on elsewhere. How did you end up working in this area?
Dr. Stiles: Well, starting at the University of Virginia, I really got attracted to the specialty of surgery. I had a lot of really great mentors. I think that’s how a lot of us do what we do. And then I got more and more interested in cancer. I spent some time at Sloane Kettering doing research and then unfortunately, my dad got diagnosed with lung cancer. I was already sort of on the pathway towards thinking about thoracic oncology at that point, but that really galvanized everything for me when I saw what he went through at that time.
Host: How long ago was that?
Dr. Stiles: That was almost 15 years ago.
Host: Well, I’m sure that you take a lot from that experience as you approach patients and think about how you guide your patients through the challenges of dealing with lung cancer.
Dr. Stiles: I definitely do, and I think you see it on both ends, on the diagnosis end but also on the treatment end. He would have been 75 just this week, so I sent something out about that, so it really made me step back and think about all the progress that we’ve made since he passed away and I do think it’s a remarkable time. I never want anybody to have lung cancer, but we just have so many more tools to deal with it now. I think he would be pretty proud of that and that makes me pretty excited.
Host: No, that’s great. It’s great that you can take that forward and certainly in his memory. So, give us for the audience and some people who are listening are probably very familiar with lung cancer, others probably don’t know much about it. give us kind of the 50,000 foot view of the big picture of lung cancer as far as how common is it, it’s one of the more common cancers and the overview that you give as an introduction.
Dr. Stiles: I think that 50,000 foot view is really important. For a very long time, lung cancer was sort of swept away or sort of stigmatized or pushed in the back. People just didn’t really want to talk about it. and often because of its association with smoking and a certain amount of shame associated with it. I’m sure we will talk about later. There is also a sense of hopelessness. Traditionally, we didn’t do well with late-stage lung cancer. A lot of the patients just didn’t do well and passed away unfortunately.
Now, as we are starting to get some good stories and starting to get this idea that anybody can get lung cancer; it’s a lot more in the news. And as you are well aware, a lot of the major advances that have been made the last several years in both targeted therapy and immunotherapy have really been in the lung cancer field.
Why it’s important? It’s the second most common cancer in men. It’s the second most common cancer in women. Prostate is number one in men, breast in women. So, if you put lung cancer together though, it’s probably the most common cancer in many parts of the world. Probably even more important other than the big picture view is that lung cancer takes more lives than any other cancer. There are almost two million deaths a year from lung cancer and in general, we think, and we say, and the literature supports it that lung cancer kills more people than the next three most common cancers combined. So, it’s about one in five lung cancer deaths. So, it really has important implications for patients, for society as a whole, for their family members. It’s a very common cancer. It is going to touch a lot of people’s lives.
Host: How do most patients present? I mean I know some people it’s with an incidental finding, maybe a screening test. Others obviously present with more advanced stage disease and a lot more symptoms. What are the rough proportions there?
Dr. Stiles: That’s a great question John. Lung cancer has not historically done as well with early diagnosis. If you’ve got a tumor growing in your lung; out in the periphery, it is often not going to cause symptoms. Where it causes symptoms is if it has spread to the lymph nodes in the middle of the chest or to other parts of your body and then it’s often too late. Historically, people presented with cough, coughing up blood, fatigue, shortness of breath; and we know that if it gets that far along, it’s often a big problem.
Now, with lung cancer screening, but also with lost of CTs being done on lots of people who walk in the hospital doors; we are finding more and more cancers earlier and we think that that’s improving survival rates.
Host: So, you alluded to the issue of the smoking connection from the standpoint of other cancers, it seems like the second question often comes up is well, did he or she smoke or and obviously, there’s a lot of ancillary baggage to that question and on some level does it matter and also kind of within the community, I’m sure that that is something people struggle with, the focus on that. Give me your take on that as you see.
Dr. Stiles: Yeah that’s a really tough topic to talk about and you definitely have passionate people on both sides. I think without a doubt the most common reason that people get lung cancer is because of previous smoking. We know that there’s a link. That doesn’t mean people deserve to get lung cancer. And it certainly doesn’t mean they should be blamed. Almost every cancer has some sort of choice or decision making or lifestyle issue that has at least contributed to it in some way. But I think what cancer patients don’t want to hear and what lung cancer patients don’t want to hear is that “oh my gosh you have lung cancer, you must have smoked.” Nothing turns them off more than that and really nothing really makes them feel more guilty or feel like they had a role in it.
Nobody deserves lung cancer and I try to avoid asking questions at the get go about smoking. Certainly, most did, but I think most of my patients have quit years and years ago. Now how we talk about that in a big context of cancer and sort of societal issues is really important. I think for the first time in – or over the last 25 years of really seeing cancer rates go down, there was a great report from the American Cancer Society showing a 27% decrease over the last 25 years in cancers. A lot of that, we have to face it has been driven by decreased smoking rates. That’s great.
As we’ve seen that go down though, we see more cancers proportionately never smokers and that’s another important topic to talk about. A lot of our patients advocates, and the patients are out there on targeted therapy are never smokers and so nothing turns them off more than this idea about lung cancer is all about smoking.
Host: So, why are we seeing more lung cancers in never smokers? I mean putting the smoking aside, something else must be happening presumably.
Dr. Stiles: Yeah, another great question. We looked at it in our group of surgical patients just recently here at Cornell and it’s remarkable to see the proportion of never smokers has increased over the years. More recently, in the most recent three years, almost a third of our patients were never smokers which is a pretty amazing number. Now I don’t know, does that mean that more never smokers are getting lung cancer or just that there’s less people smoking so proportionately we are seeing the never smokers come higher? That’s a big question that a lot of people are interested in and trying to answer.
But we know that the things that contribute to lung cancer never smokers, radon exposure is probably the most common so get your homes checked for radon. Probably environmental factors are playing a big role and we are starting to see that a lot in Asia or other countries where there’s a lot of air pollution, that rates are starting to spike a bit there. Certainly, there is probably genetic components that we just don’t understand yet or understand about. That’s probably also this idea that some patients with driver mutations, certain ethnic minorities are more predisposed to those types of cancers, so we know that there must be some genetic component as well.
Research is hopefully going to solve a lot of those things for us. But we are certainly seeing lots of patients who are never smokers.
Host: So, I’m intrigued by the radon question and I’ve read about it, but I haven’t delved into it. So, what is the – what’s the connection there? I mean is it a tight connection? How do you tie that together?
Dr. Stiles: Again, I’m certainly not an expert in the field but actually I’m told that radon, the link of radon to lung cancer was actually made before the link to tobacco smoking and lung cancer. So, it’s been a long-known association and I think it is just inhalation injury and repeated DNA damage that then leads down this pathway to cancer. And then so people, it’s easy to check. Easy to know. So, I think that’s something low hanging fruit to –
Host: So, there’s been a lot over the years, and I know a big focus is in lung cancer screening. Like any screening test, there are complicated issues around that. Obviously, the idea of who to screen, who has got the highest risk and therefore the highest yield, false positives which is clearly a big issue in lung cancer as well as other cancers. Are you going to find tumors that you need to know about that you’re going to change the natural history by finding them early? A lot of things in there. What’s kind of the latest and I know this is a moving target, but what’s kind of the latest or what would you tell someone let’s say with either no risk or some risk as far as how to approach that and think about that?
Dr. Stiles: It’s remarkable. Lung cancer screening really came of age in an era in which there was more skepticism about cancer screening in general and so that’s put a lot more of the pressure on people who advocate for lung cancer screening. But that said, I think lung cancer screening has some of the best data out there for any screening. There was a study called the National Lung Screening Test with over 50,000 patients that showed quite convincingly a 20% reduction in mortality if you get screened.
How those numbers played out and can be twisted around a lot of different ways and so that’s important to know. There’s a second study coming out of Europe that was discussed this year, but we are waiting to see it published called the Nelson Study which showed that the benefit maybe the risk reduction may be even higher in men and even tantalizingly even higher in women. So, 40-60% a different screening than it was for women. So, clearly, I think there’s data out there to support the idea that screening works.
Now how do we get to the implementation is a really important question and what are the bad things from screening is the other important question. And again, you can argue that a little bit of the stigma of lung cancer has kept this in the wings and kept the numbers of patients screened down, this sort of nihilism that eh, they smoked, they are going to get lung cancer, lung cancer is maybe incurable anyways, so why should we screen. But that’s really not the case. Again, we’re talking about studies that show a mortality benefit to patients who are screened. We are talking about moving the diagnosis. So, one of the things you had talked about earlier, how do people present with lung cancer. If you look at all comers, it’s a little bit unusual because over 50% present historically with stage 4 disease. Compare that to prostate and breast where that number is much lower where 80-90% present with local or local regional disease and you can see that you have a problem. We have to find lung cancer earlier.
Screening does that. So, over 60% in most of the big screening studies were found at stage 1. That, we know that we can cure or at least get a jump on. Now back to the bad stuff. So, you used a term false positive. That term always makes me crazy and no offense to you, but this is really what’s been played up and so if you look at some of the things that people have published about lung cancer screening, they’ll say well, three in a thousand fewer people will die from lung cancer with screening, but two in a thousand will have a major complication. And you’ll find a false positive in over 200 in 1000 patients.
A nodule found on lung cancer screening to me is not a false positive. Right, and a lot of people have nodules. We can look out here at everybody walking around on the city streets and if we scan them all, about 20% will have some nodule. To me, it’s only a false positive though if we choose to work it up and go down this pathway where we are worried it’s lung cancer, we are doing invasive studies and taking it out and doing things; then it’s a false positive. Otherwise, it’s just a nodule and we know that most of those are going to be benign. We can follow those with normal CT scans and never have to do anything to those people.
Now the complication rate is also played up that people are going to have all these complications from lung cancer screening, I think is a little bit distorted by the positives. So, if you look at the numbers, they said two in a thousand will have complications from major procedures. Again, this is published by NCI and other groups. But really, that’s all comers. If you take the patients who are found not to have lung cancer, it’s like 6 in 10,000. It’s really the lung cancer patients who go on to get procedures, who go on to get therapy, who go on to get treated, who have maybe complication rates of 10-11% that drive that number up.
This is just a CT scan. It takes less than a minute to do. If we are educated about the nodules and how to follow them, which we are now with great programs called Lung-RADS, there should be very little harm to CT screening.
Host: So, who should get screened?
Dr. Stiles: Yeah, great question. That too, creates a lot of discussion in the advocacy world, right? They want – people want access for everybody to be screened. But I stick strictly to the criteria which the randomized trials shown, and most do and so screening was just approved by CMS in 2015 and it’s really people aged 55-70 and it’s really got to be people with a heavy smoking history. Meaning more than 30-pack-years or a pack a day for 30 years. the more controversial criteria is that they have to have quit within the past 15 years which excludes people who quit many years ago, but I think it’s important for us. Now you can say well what does that get you and if we look at all of our lung cancer patients that I treat surgically, only about 30% would fall into that criteria.
So, some people say we need to screen everybody, and they pound their fists on the table and they say I’m a never smoker, I should be screened. And I understand that. If you are affected by lung cancer, you want to get there. But first we need to do well with the group that we know that it works and that we know that it’s been approved and that we know we have careful clinical trials. And so I think we really need to stick to the screening guidelines and to really work through that to show that we can get rates up and do it safely and then over time, we’ll expand into other groups.
Host: What are the typical options that when you are seeing patients as far as biopsy, surgical procedures. How does that usually go or what sways you one way or another?
Dr. Stiles: There’s lots of options and it’s really hard I think to lay it out on a global basis. Really, there is a lot of individualized care that goes into this. I think the first criteria is seeing that the nodule is there and that it has persisted on multiple scans, you don’t have just a quick trigger finger to any nodule that needs something. Because most are going to be benign. If you see a persistent nodule that looks suspicious our general philosophy is to try to get a biopsy first before doing a therapeutic procedure. I think that’s safe and that sort of decreases this idea of harming patients who don’t have lung cancer. And there are lots of ways to get biopsies, CT-guided, bronchoscopic. Sometimes we will take a patient for a surgical biopsy if we are very suspicious. But I think for people out there at other places, just do what your place does best. If they are better at CT biopsy, do that; if they are better at bronchoscopic biopsy, do that. And often getting more information first, PET scans or other sort of data points that you can use to help determine the likelihood that it is a cancer.
Host: What is the typical scenario?
Dr. Stiles: Well here is the problem John it really falls on the responsibility of the primary care physicians and I think they are the group that has least embraced lung cancer screening. And that may be historically based on biases and maybe on the fact that these are incredibly busy people who have a lot of things going on. One of the interesting requirements of lung cancer screening is that it was only approved with a shared decision making visit. It’s a little bit unique from cancers in that you have to have this discussion about it.
That’s a little intimidating for primary care physicians or others who aren’t thinking about lung cancer all the time and may not be up to speed on the data about screening. A lot of screening programs have tried to make that easier by saying we’ll have that decision making conversation if you as a primary care physician refer the patient to us for screening.
Ultimately, it’s going to come down to the primary care physicians to recognize and identify which patients meet the screening criteria and then to get them into screening systems.
Host: So, on the surgical side, what are kind of my time in the operating room goes back a couple of decades in medical school. What I recall the most is big operations, chest tubes, pain because people have pain every time, they take a breath. Clearly, the field has moved, and I know from my own patients that we shared, into many more cases being manage through minimally invasive and newer kind of techniques. Can you give us kind of a quick overview.
Dr. Stiles: Yeah, it’s really fun to be a lung cancer surgeon now. We have a lot of great tools as our disposal and when I give the lecture to the med students, I always show the pictures of the guy almost getting cut in half and having his whole lung taken out to the guy getting partially cut in half to the little incisions to even the surgical robot. And it really has evolved over time. I think at Cornell, over 90% of our lung cancer operations are minimally invasive with two or three little small incisions which we think is pretty good and pretty remarkable.
We think that really helps patients get over the surgery quicker. We think we can still do the same cancer operation through those small incisions. We’ve shown that it leads to less complications over time. We are increasingly trying to refine that and to – whether it’s with the robotic system, whether it’s with other minimally invasive platforms and to do better smaller incisions that are less painful. And increasingly, we are starting to look at the idea of not just little incisions, but can we take out less lung. Can we do lung-sparing surgery to give these patients who are going to be hopefully they are going to need their lungs for the rest of their life, so we want to save as much as we can in the confines of still doing a good cancer operation.
Host: So, from the standpoint of taking care of these patients, it seems like a multidisciplinary team is pretty important. What’s kind of the state-of-the-art from the standpoint of involving the radiation oncologists, the medical oncologists in different cases? Kind of how does that typically work and the advantage of a center like here that has the team that can kind of all put their heads together fairly efficiently.
Dr. Stiles: I think that’s critical and we really emphasize multidisciplinary care and I think a lot of people out there in the know about lung cancer really do, because it is such a fast moving field, particularly as you get to the more advanced stages and how you are going to do that may be different at three different places and so you really do need a lot of input and it’s pretty nuanced per the patient.
For early stage disease, the radiologist touches the patient, the pulmonologist touches the patient, the surgeon touches the patient, for some patients radiation therapy, stereotactic radiation is an option and so we try to discuss all these cases at our multidisciplinary tumor board and really tailor the treatment to that patient who is right in front of us. Granted, that’s hard to convey who that person is to everybody sitting in the room sometimes. But I think that’s a really important part of what we do.
As you go up stages to stage 2, stage 3 where you might have potential different treatment paths, sometimes chemo first, sometimes immunotherapy first, sometimes surgery first; it becomes even more important to layer in all those opinions and to make sure that we are doing what’s right for our patients.
Host: So, immunotherapy is a big buzz word and you just alluded to using that before surgery in some cases; why is immunotherapy so relevant to lung cancer? I mean there are certain other cancers, obviously, but why lung cancer in particular?
Dr. Stiles: Well it’s been amazing. I mean it has really revolutionized lung cancer and if you look just back from 2015 to now, who gets immunotherapy is amazing. We think lung cancer is kind of a smart cancer, people have described it. There is dumb cancers and smart cancers. The dumb ones are really driven by one or two mutations and don’t have a high mutational complexity. Lung cancer is pretty smart though, right, it’s got a high burden of mutations. It’s got ways to get around other therapies. And while that’s bad for standard therapy, chemotherapy and targeted therapy, may be it’s good for immunotherapy because it means they’ve got a lot of things going on. The body recognizes that this shouldn’t be happening, they say it’s foreign and so it can harness it’s immune system to help fight it.
Immunotherapy really can’t be a stage 4 lung cancer patient unless you have a specific targeted mutation and not get immunotherapy these days. If you have over 50% expression of a certain protein, you might just get immunotherapy alone. Which is pretty remarkable to think about. You must be a stage 4 lung cancer patient and not get any chemotherapy now and quite a few don’t.
Even if you don’t have high expression of that protein, immunotherapy often comes into the frontline for a current stage 4 lung cancer patient.
Host: So, a big buzz word is precision medicine and precision therapy and immunotherapy is a part of that. I know that going back years, someone would have surgery or get a biopsy and it would be histology. You just say it’s small cell, non-small cell adeno, squamous, etc. Now there’s a whole panel of things that get checked and how would you say that’s kind of impacted things and from this state-of-the-art of what a patient should have done when they are diagnosed these days?
Dr. Stiles: Yeah, another really remarkable thing and again, the thing that I show the med students every time I talk about this is just how we have evolved, and I show a chart, when I started giving the lecture, that talks about treatment of stage 4 and it just said chemotherapy and consider targeted therapy. And then I show this chart that somebody actually made and sent to me on Twitter that’s got all these crazy pathways depending on what you have here, there, wherever, everywhere and so many different options which is just incredible to think about.
For us, the really – lung cancer is not just one cancer like you say. It’s really a host of cancers. Some driven by driver mutations like EGFR or ALK or ROS1. Even the ones that don’t have those, then we look for expression of an immune protein, PDL1 to sort of segregate how they are going to be treated. And so there’s multiple different pathways.
And even for us in the earlier stage disease and in resectable disease; these things are starting to become important. It’s not just as you said, small cell and non-small cell. Now it’s adenocarcinoma, different subtypes of adenocarcinoma are some of those more amenable to lung sparing surgery than other ones. Do we need to take out the whole lobe? Can we save some? And so these things that – it’s really pathology, right? Pathology matters. And the tissue is the issue. It really tells us how we are going to treat lung cancer and so I think any center where you are, should put a priority on having an excellent pathology service in checking all these mutations and histologic subtypes in lung cancer.
Host: So, are a large percentage of patients getting some sort of systemic treatment before surgery?
Dr. Stiles: Another good question. And really Nasser Altorki who is my boss has really been a leader in this idea. This idea of window of opportunity trials. So, can we give a drug into the patients before we take it out to number one, improve their survival, number two to improve our ability to resect those patients. There’s been a couple of trials with targeted therapy to try that. There’s another one going to be rolling out again for that, a national trial.
Here at Cornell right now, we are interested in giving immunotherapy preceding surgical resection and that’s not novel. There are lots of places excited about that too, with the immunotherapy wave. But we have a great trial that where we combine it with small doses of radiation to try to immune prime the patients. And we are seeing some remarkable responses. That’s mostly for late stage 1, stage 2 and stage 3. For early stage 1 which is still most of our surgical patients, they are still going straight to surgery. But for that in between stage 1 and stage 4, that’s really where we think we can move the needle with some of these trials before surgery.
Host: So, I know a big part of what you do is research in this area. What are some of the things you’re working on and what do you think is also big in the field that people ought to keep an eye on?
Dr. Stiles: Well everybody is interested in the immune system, how that interacts with everything else and so, that’s our lab is really focused on that and that’s again led by Nasser Altorki and Tim McGraw, we have partnered with a lot of great scientists. We really think that studying patient material and then sort of looking in the lab and then bringing it back to the patients is the way that all this should work and so we put a big emphasis on that. We are trying to understand the immune microenvironment in these cancers and trying to understand why one may respond to immunotherapy and why another won’t, how we can boost one up with radiation therapy to make it more immune responsive. I’m particularly focused on a protein that I think may sort of serve as a check point inhibitor kind of like the more classic check point inhibitors PDL1 and the role of that in immunotherapy.
Lots of exciting things going on there. Our group as surgeons has always been interested in biomarkers and again how do we segregate patients but how do we go back to that screening idea and if we have a patient who has a CT scan with a nodule, can we figure out more about it than that? Is there some blood marker we can find? Is there something else about the patient that will tell us this is more likelihood of cancer?
Those are big things in the field and then resistance to targeted therapy. So, one of the things we haven’t talked about as much and that’s really changed the face of lung cancer is EGFR based therapy, ALK based therapy, ROS 1 based therapy. These patients are doing so well now. There was actually an amazing report from the University of Colorado recently that showed almost a seven year survival with stage 4 ALK rearranged lung cancer. Amazing when you think about the standard survival for a stage 4 patient is less than a year. But the patients are doing so well, they eventually develop resistance to these drugs and so finding the second way around or the next generation drug that works for that or finding ways to combine with other therapy like immunotherapy or chemotherapy is a big focus of research right now in the lung cancer space.
Host: And what about prevention? From the standpoint I know a big risk factor of getting a lung cancer of having had one before and I know one of the things you think about in your patients is when they’ve been cured of one lung cancer, avoiding another one and I’m going to ask you also about totally unrelated but connected a little bit this whole issue of E-cigarettes and changing all of that. Because I know nothing about that. But I know it’s getting a lot of attention from the FDA. So, not to come back to smoking, but those two points.
Dr. Stiles: Well the E-cigarettes and vaping is a great issue. I’ll come back to that in a second. I think prevention is largely by stopping tobacco products. And I think that we sort of – I always say the golden moment to stop smoking for patients who still do it is when they are in the hospital after they have had surgery and we really believe that in screening programs there’s always or there’s also evidence that smoking cessation programs, they work well there. And then it’s just other things. It’s hard to put a pinpoint on nutrition, air quality, exercise probably have some role.
Back to E-cigarettes and vaping, I have spent a lot of time thinking about that lately and on the – it’s an amazingly polarizing thing. Like if you talk about some of the things that I have put on social media that’s I’ve gotten the most negative comments on, it’s been comments about vaping. I think that first of all, they are potentially a great adjunct for patients who are trying to quit cigarettes. And there was just a New England Journal paper that showed that double the rate of quitting tobacco at one year. The problem though is that really that there has been this onslaught of young people using these E-cigarettes and vaping and this idea of flavored vaping and all these things and also from the New England Journal showing that an eight to ten percent increase per year in vaping in teens. That means over one million new vapers a year. It means almost 20% of 12th graders are using E-cigarettes.
That has incredible implications and we were fooled once by cigarettes. It’s an amazing story about the denial of the link of tobacco with lung cancer. Certainly, E-cigarettes are safer, but there’s also some suggestions that they are not totally safe. And I think whether we want to introduce teens to that or introduce them to nicotine which is potentially a gateway to regular cigarettes; that’s an issue that we have got to pay a lot of attention to.
Host: So, I want to wrap up with just your thoughts on your advocacy, because I know you’re involved with the Lung Cancer Research Foundation, you are out on social media. Advocacy can be a very powerful thing. I’m not sure that the Lung Cancer community has been as strong as perhaps others given the number of people affected by it. But clearly, you put a lot of time and effort into it so you think – and I agree, I do the same thing in the lymphoma community; what advice do you have about patients, family members, potential advocates out there as to the value of these sorts of efforts and how would you suggest that they get engaged one way or another?
Dr. Stiles: Well first of all, it’s an understatement to say you do the same. You’re amazing. So, I have seen your career and what you do for advocacy has really been sort of inspirational to me. When I went to the Lymphoma Foundation Research and saw them honor you, it really is amazed and remarkable.
I think all physicians should be advocates for the diseases that they treat if they really believe in it and really believe in the patients there. It’s tough though for a disease like lung cancer and you have to approach patients. Not everybody wants to be an advocate or put themselves out there. But I think that is still historically based on some of the stigma associate with it.
I love talking to patients. I love for patients to share their story whether it’s good stories or sometimes bad stories. But we try to get them involved with talking to our medical students. I was amazed this year, they gave me an extra half an hour to talk to the med students and then I realized it was just they wanted to hear the patients more and not me. And that rings true though. People want to hear patient’s stories. People want to understand how if affects their lives. They want to know about how lung cancer can affect anybody. So, there’s increasingly on social media and things like this, there’s more of a push in lung cancer for people to share their stories. And I think that’s critical for the disease. It’s critical for making a link for research in patient stories.
Host: Great, so before we wrap up any other messages or take home messages beyond that, for patients that you would suggest as they think about dealing with a lung cancer?
Dr. Stiles: Well I think share your story. I think get lots of second opinions. I think it’s a complicated disease and like a lot of the cancers that we treat here at Cornell, there may be some benefit into seeing a center of excellence or seeing experts in the field. Don’t be alarmed if they say different things and again don’t be afraid to go get treated in your community. That’s just as important too. But I think don’t miss the opportunity to make sure that you are getting the right treatment because like you said John, lung cancer is not just small cell and non-small cell, there’s so many nuances now and the field is moving so fast, it’s hard for people to keep up with. So, be your own advocate for your disease. Ask for second opinions. Ask what’s happening out there in the lung cancer world and share your stories most importantly.
Host: Great. Well this has been a fabulous discussion. Thank you for joining us and I have a feeling we’ll have you back again before too long to talk about all the progress. So, I want to thank our audience for joining us. And I want to encourage you to download, subscribe, rate and review Cancer Cast on Apple podcasts Google Play Music or online at www.weillcornell.org. We also encourage you to write to us at cancercast@med.cornell.edu with questions, comments and topics you’d like to see us cover more in depth in the future. That’s it for Cancer Cast: Conversations About New Developments in Medicine, Cancer Care and Research. I’m Dr. John Leonard. Thanks for tuning in.