Transcription:
Lung Cancer: An Overview

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 on the podcast, we'll be talking about all aspects of lung cancer.

Our guest for this episode is Dr. Ashish Saxena, a medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital. Dr. Saxena specializes in treating cancer of the lung and thymus as part of the thoracic oncology program. He cares primarily for patients with non-small cell and small cell lung cancers, mesothelioma, thymoma and sarcomas of the lung. Dr. Saxena is involved with both clinical and laboratory research focused on the study and management of these cancers, and I'm really looking forward today to discussing the newest updates in research, treatment and care of lung cancer patients. So, Ashish, thank you for joining us today. It's really great to have you.

Dr. Ashish Saxena: (Guest) Thank you so much, John, for having me. It's a pleasure to be here.

Dr. John Leonard: (Host) So, I'd like to start by getting a sense of what drew you to the field of hematology and oncology in general. And in particular, what drew you to focus on the area of lung and thoracic cancers specifically?

Dr. Ashish Saxena: Sure. So, I think initially my interest in oncology came from the research side. When I was in medical school, I was also in an MD-PhD program, so I was doing my PhD in genetics and got some exposure to cancer research at that time. But mainly, what drove me into oncology and lung cancer specifically was a personal story. My mother, while I was a graduate student, got diagnosed with lung cancer. She was young, only about 58 years old and she had never smoked, and this came on very suddenly. And she unfortunately didn't respond well to the treatments that were available at the time and she passed away very quickly after only about two months. And that really drew me into the field specifically of lung cancer and learning more about it and studying it to try to help make some changes and improve the lives of patients with lung cancer.

Dr. John Leonard: (Host) Well, thanks for that background. And I know that lung cancer is one of the more common cancers that's out there. And your own personal story, I think, highlights the fact that many of us are affected by this either directly or indirectly just because it is so relatively common. One of the aspects of lung cancer that I think is important for people to understand is the fact that there are many entities that fall under the name lung cancer. So, maybe you can tell us about the more common types within lung cancer. And then, we'll also talk a little bit about the other thoracic cancers that are not specifically lung cancer. So, what are the main subtypes of lung cancer?

Dr. Ashish Saxena: So, as you said, it's one of the most common types of cancer. It's the second most common type of cancer in men behind prostate cancer and in women behind breast cancer. But it is the most common cause of cancer death. In terms of the types, there's different types of lung cancer. Of the cancers that originate in the lung, we broadly classify them into non-small cell lung cancers, which are the most common, about 85 or maybe even up to 90%. And then, small cell lung cancers, which are maybe 10% to 15% of lung cancers. And within the group of non-small cell lung cancers, there are also different types. Adenocarcinomas are the most common type as well as squamous cell carcinomas, large cell carcinomas. So, these are classifications that pathologists generally will tell us when they do a biopsy and look at the cancer under the microscope. And then, small cell lung cancers are a separate type of lung cancer, which also originates in the lung, but they tend to be a little bit more aggressive and grow more quickly than the non-small cell lung cancers as a whole.

Dr. John Leonard: (Host) And then, there are a number of other cancers that fall outside of "lung cancer," I presume largely because they're formed by or stem from different cell types, but can occur in the chest. What are some of those?

Dr. Ashish Saxena: So, mesothelioma is one that's very closely associated with asbestos exposure, and that generally comes from the lining of the lung where there are mesothelial cells. And thymomas come from the thymic gland and they can be more benign or they can be more aggressive, in which case they're called thymic carcinomas. And then, there are other types of cancers like sarcomas, which can happen in different parts of the body, including in the lung. And then, other types of cancers that may have started somewhere else outside the body may spread to the lung and they're classified as from where they began, whether it be a breast cancer or a kidney cancer, but they can then spread and we may find them in the lung.

Dr. John Leonard: (Host) So, it seems like one of the aspects of lung cancer that is important, like with many cancers, is the risk factors that are associated. And I know that historically most people will associate lung cancer with smoking. But there are a lot of patients who either have other exposures or have never smoked and have no clear exposures that ultimately develop lung cancer. So, how do you sort all of that out?

Dr. Ashish Saxena: So, smoking is still the most common cause of lung cancers. And the good thing about that is that as we've cut down our smoking in the country and in the world, the rates of lung cancer have gone down. There are other causes of lung cancer. And sometimes we don't have a known cause, particularly in patients that have never smoked. In some studies, one out of 10 men and one out of 20 women in the US are never smokers with lung cancer. And if you look at other populations such as East Asian populations specifically in women in those populations, most of them are never smokers. And so, it is important to note that you don't have to be a smoker to get lung cancer. Sometimes it happens even if you've never smoked. And those patients that have a lung cancer that have never smoked often have specific genetic alterations in their tumors, many of them which we can target.

In addition to smoking, other things that are risk factors can be environmental, like secondhand smoke. So even if you are not a smoker, if you've been around smoke a lot, that can increase your risk. Some chemicals like radon, certain metals and then pollution in general including indoor coal and wood cooking, those things have been related to lung cancer.

Sometimes treatments that we give for other cancers can lead to lung cancer, specifically radiation therapy, which might be given for a lymphoma or breast cancer. And other diseases may also predispose you for lung cancer, things like a COPD or a chronic obstructive pulmonary disease and pulmonary fibrosis. Unlike breast cancer, where there may be one specific gene that we look for in terms of family history, we don't have that so much in lung cancer. But it has been shown that people with family histories of lung cancer seem to have a little bit higher risk of getting lung cancer than those that don't.

Dr. John Leonard: (Host) Radon has struck me as one that's a little bit unusual in that you really don't have any sense of your exposure to it. I don't know how commonly people are looking at their houses. I guess that's the main site of exposure to radon.

Dr. Ashish Saxena: It's not something that most people think about. Many of them, we don't know where the lung cancer may have come from. But, we do say that, and sometimes a patient may go back and try to inspect their house for radon. But I can't say that it's been a very common thing that I've come across, that someone has had a large radon exposure. It's just something that they've shown in studies to be associated with lung cancer.

Dr. John Leonard: (Host) So before we move on from risk factors, for someone who's been a smoker or who is a smoker, from the standpoint of lung cancer risk, will stopping smoking reduce their risk? And what if they even have a lung cancer, will stopping smoking impact them as well? How do you think about that in patients who come to you with a smoking history?

Dr. Ashish Saxena: So, definitely cutting down and stopping smoking is one of the first things we do recommend even for patients that have a lung cancer. Those without a lung cancer, it definitely cuts your risk down, especially as more time goes on from when you stop smoking to getting a lung cancer. But even those patients that have lung cancer, if the smoking caused or predisposed the lung cancer, even if let's say we cure the lung cancer with surgery, if you're continuing to smoke, you're continuing to expose yourself to that damage. And so, you are more likely to get another lung cancer. And so in that case, we also very strongly encourage patients, even once they're diagnosed, to stop.

Dr. John Leonard: (Host) There are some interesting statistics out there that the funding for lung cancer research is relatively low, given the prevalence of it that it's one of the most common cancers. I'm wondering, do you have any thoughts on why that is? Is it because of the stigma attached to smoking or any other thoughts around that?

Dr. Ashish Saxena: It's true that for lung cancer research funding, it's definitely lower than other types of cancers. And I do think that the stigma plays a big part in that. A lot of times patients are ashamed, or they feel bad that, "Oh, I did this to myself. I was a smoker," when they shouldn't feel that way.

First of all, there are many patients that never smoked and get lung cancer. And even otherwise, nicotine is an addictive substance and it's not easy to just say, "I'm going to stop smoking.” Sometimes patients feel, uneasy, even when I ask them, “Did you smoke?" or "How much did you smoke?" You can tell they feel uncomfortable because they feel like you're going to judge them that, "Oh, of course you have your lung cancer because you smoked," which isn't really the case.

Dr. John Leonard: (Host) So, let's move now to diagnosis, from the standpoint of patients diagnosed with a cancer, what are the common ways that patients are diagnosed or what leads them to seek medical attention with a diagnosis of lung cancer?

Dr. Ashish Saxena: So, sometimes patients will present with symptoms such as cough, coughing up blood particularly, having trouble breathing, feeling short of breath. Sometimes there may be some pain in the chest area. Sometimes patients will present with a hoarseness in their voice because of the location of the tumor pressing on certain nerves. Sometimes they may present with a pneumonia because the tumor is obstructing the normal airflow and predisposing them to getting an infection, so they may come in with a pneumonia and, on workup, might find that there's a cancer beneath that.

And then, sometimes they might be incidental. We get a lot of scans these days for different things. Sometimes people are being worked up for a knee surgery or some other procedure and they happen to find this. But the way we'd like to find these is mainly with lung cancer screening.

Dr. John Leonard: (Host) So, I guess the question then is who should get screened and how one thinks about screening, knowing that there can be false positives and a lot of discussion about either the risk of screening or the cost of screening. I know that's been a moving target from the perspective of CT scans and other screening tests. How should people think about that and who should be screened?

Dr. Ashish Saxena: So, there has been, so far, two larger studies that have shown the benefits of lung cancer screening. One was the National Lung Cancer Screening trial that was done here in the US. It looked at about 53,000 participants. They were ages between 55 and 75. They were smokers, so they're at high risk and the patients got randomized to either get a low-dose CT scan every year for three years or a chest x-ray. And what they found was that there was a much higher rate of finding the lung cancers at earlier stages, so stages where they were curable, with a CAT scan compared to the x-ray. And that translated into a 20% reduction in lung cancer-related mortality or death. And that was also seen in another trial that was done in the Netherlands which was called the NELSON trial. And that also looked at a population of high-risk individuals who got lung cancer screening with CAT scans at baseline and every year. And they again found that there was up to a 26% reduction in lung cancer related mortality in men and even higher in women.

So, both of those really showed that lung cancer screening does save lives. It does increase the chances of you finding the lung cancer at an earlier stage where it's curable and your prognosis is better. And that has been shown to be cost-effective in other studies, such that right now the United States Preventive Services Task Force recommends that people that are between age 50 and 80 that have 20-pack year smoking history, which basically translates to smoking one pack a day for 20 years and are either still smoking or quit within the past 15 years, that those people do get an annual low-dose screening to pick up lung cancer. So, that's the population that was studied in these trials. And since they did show a reduction in mortality, that is recommended by not only the US Preventive Services Task Force, but a number of other societies such as the American Cancer Society and the American College of Chest Physicians and so forth.

Dr. John Leonard: (Host) So, there's really no screening for someone without a smoking history, it sounds like. Those just either present with symptoms or incidental findings. Is that correct?

Dr. Ashish Saxena: So, in terms of what's recommended by the associations, mostly based on the trials that I mentioned, it is for smokers or past smokers. So, someone who's a never smoker, they don't really fit into the studies so far. But there are studies going on looking at people with family histories or other things. So, we're not quite ready to say the benefit would be there for everyone to get CAT scans every year. Right now, it's focused on the high-risk individuals, which are mainly the smokers at this time. But in the future, those might change, especially since there may also be screening modalities other than CT scans. People are looking at doing blood cancer screenings, looking at circulating tumor DNA in the blood, and those may be able to pick up cancers even better than the CT scans and maybe for other patients besides just the smokers.

Dr. John Leonard: (Host) For patients who undergo screening or have a symptom and get either a chest x-ray or a scan, it seems like the most common scenario is that they have a nodule or a mass on imaging. And the next step is presumably to figure out what it is. So, what are the procedures that patients commonly undergo if they're screened or assessed for some symptom and found to have an abnormality on their imaging?

Dr. Ashish Saxena: So generally, the first thing is to figure out what it is to confirm that it's a lung cancer, what type of cancer, what type of lung cancer even. So, they often will get that done with a biopsy, and that may be through a bronchoscopy where a pulmonologist or surgeon may go in through the throat and into the lungs with a scope and get biopsies that way, or by an interventional radiology procedure where an interventional radiologist can use images to use a needle to go in from the outside to get a piece of either the lung or some other suspicious lesion. And then, that all gets sent to the pathologist to see what type of cancer it is and do further testing on it. After that, we want to see where the cancer may have spread to. So in addition to CAT scans, we often do PET CT scans to see if we can pick up the cancer anywhere else outside where we saw it initially. And also, MRI of the brain is common because lung cancers do tend to spread to the brain. It's generally standard to get an MRI looking at the brain if possible, particularly if the cancer seems more advanced at first presentation.

Dr. John Leonard: (Host) So I remember, even though I don't take care of patients primarily who have lung cancer, the complicated staging system: looking at the size of the tumor, the number of lymph nodes and where they are, and then whether or not there's more advanced disease. Once a patient has some staging done to see where their tumor is, it sounds like they're classified into a couple of groups, whether that's limited or advanced stage. What is the process after that, from the standpoint of thinking about treatment at a high level, recognizing there are a lot of different situations?

Dr. Ashish Saxena: Generally, the non-small cell lung cancers, which are the most common type, when they're only confined to the lung and haven't spread to lymph nodes in the chest, they're generally treated with surgery alone. And if a patient is not able to undergo surgery, then a radiation procedure of just that tumor is what's done. When the cancer has spread to certain lymph nodes in the chest, then surgery is still often able to be done, but there's usually recommended some other treatment, a systemic treatment or something that goes throughout the body, and that's generally been chemotherapy either before the surgery or afterwards.

Now, sometimes the tumor is advanced enough where they don't feel that surgery's feasible or possible, but it still hasn't spread to other organs. And in those cases, radiation is generally the standard treatment, again with chemotherapy.

And then finally, in the most advanced stages where the cancer has spread outside of the lung, then the mainstay of the treatment is the systemic therapies or things that travel throughout the body, such as chemotherapy and some of the other newer therapies.

For small cell lung cancer, there are similar modalities. Surgery is very rarely done for small cell lung cancer because it's often found more advanced. But if it is picked up at a stage where there's only one tumor and no other evidence of spread, then sometimes surgery can be done. But most of the time for small cell lung cancers, the treatments, if it hasn't spread, is chemotherapy and radiation. And if it has spread, then again it's mostly the systemic therapy base, so things like chemotherapy.

Dr. John Leonard: (Host) What are some of the chemotherapy drugs that are commonly used?

Dr. Ashish Saxena: So for the chemotherapy, most of the lung cancers are treated with what we call a platinum doublet. So, they're platinum chemotherapy-based, which can be cisplatin or carboplatin, and that's usually combined with another chemotherapy drug. So in small cell lung cancers, the standard for a very long time has been platinum plus etoposide. Whereas for the non-small cell lung cancers, there are a number of agents. Alimta with cisplatin is very commonly used for non-squamous cell lung cancers. And squamous cell lung cancers are often treated with a platinum and gemcitabine or a taxane like Taxol or Abraxane.

Dr. John Leonard: (Host) As you alluded to, there are a number of new targeted therapies that are employed in the treatment of lung cancer. How does one determine whether a patient might be a candidate for one of those and where do they fit into the therapy approach?

Dr. Ashish Saxena: So, targeted therapies we've really had a lot in non-small cell lung cancers particularly. What I usually tell patients is that they only work if your tumor has the target. So in order to know that, you have to test the tumor for different mutations. Now, all cancers have mutations or changes in their DNA that make them cancerous, but some of them are what we call driver mutations. So, they're changes in the tumor that we think are really driving the growth of the tumor. And if we can block that, they will have some response. And there's a large list now in lung cancer of targetable mutations, which we have treatments for. Many of these are tablets or pills. And so, one of the things we do is make sure that the tumor gets tested, particularly for non-small cell lung cancers and adenocarcinomas, which are the ones that most commonly have these mutations. We test them for the presence of the mutations. And if they're there, you might be a candidate for a targeted therapy. Initially, this was really for the more advanced stages, the stage IV where the cancer has spread. But some of these are now looked at in earlier stages, such that even in patients that have disease that can be removed by surgery, there's been studies to show that at least one specific targeted therapy, called Tagrisso, for patients that have an EGFR mutation, then that's been shown to improve survival after surgery when given for three years. So now, the targeted agents are starting to be looked at in earlier stages, whereas initially they were mainly focused on the stage IV or more advanced patients.

Dr. John Leonard: (Host) What percentage of patients have mutations that make them eligible for one of these targeted therapies? And also, I assume that despite the fact that these are not chemotherapy, they still have side effects. So, what are some of the key side effects that can still happen?

Dr. Ashish Saxena: So, the chances of having the mutations depend on different things. So depend, one, on the type of mutation or the specific mutations. So, the EGFR mutations are the most common. And in probably the Western populations, it's about 15% of patients; more likely to find them in someone, again, who's a never smoker. In the East Asian populations, it's a higher percentage. As I mentioned, in some women, it can be over 50% in some studies. Other mutations may be less common. So, things like ALK mutations are maybe about 4%, others may be less. Most of these are mutually exclusive. So if you have one, you're not likely to have the other, so you can kind of add up the percentages and see that if you're looking for a mutation, 20% to 25% of the patients may have some mutation that might be targetable. And as we get more targetable agents, that number goes up.

In terms of side effects, they have different side effects. One of the common ones for particularly the EGFR mutations are things like rash and diarrhea. The drugs that target them have a lot of those side effects. Some of them are unique to the drug. For example, alectinib is a drug that we use for ALK mutations and that can cause muscle aches and some inflammation in the muscle, rarely. So, we watch out for those. Most of them are pretty well-tolerated when you compare them to chemotherapy. But as you said, they do still have side effects that we have to watch out for.

Dr. John Leonard: (Host) So, a percentage of patients with lung cancers are cured either primarily with surgery or one of the other local therapies, maybe a smaller percentage in people that have systemic involvement. But what is the usual strategy if the disease comes back after the initial therapy?

Dr. Ashish Saxena: If the disease comes back, it depends on how it came back, meaning did it come back and it's now more spread out and we have to kind of go back and focus on some systemic therapy and what did they have before. Or if it came back locally, let's say, and you had surgery, but it came back and it was only in one spot, you might treat that with surgery again or radiation to that area. And again, depending on how long it was, if it was an initial diagnosis at one point and, five years later, another lung cancer came back and you could treat it with surgery, you might just stop there. If it came back relatively sooner, you might even after you treat it with a surgery or radiation, consider some systemic therapy with the idea that maybe this is going to come back again soon, so you want to do more to reduce that risk.

Dr. John Leonard: (Host) Very briefly. I just wanted to take a second about the usual approach for some of the other cancers of the chest that are not lung cancer such as mesothelioma, thymoma, sarcoma. It seems like those are primarily treated with surgery when applicable, Is that correct? Or what other things are used for them at a high level?

Dr. Ashish Saxena: So, surgery for thymoma definitely is the standard and for many sarcomas if they're isolated. Mesothelioma often is difficult to treat with surgery, it tends to come back. And the surgery is very involved. There, chemotherapy had been one of the standard treatments. But now, we've also got another class of treatments, which are involved in multiple cancer types, which is the immunotherapy, that's also now approved for mesothelioma. And the immunotherapy drugs are drugs that are different from chemo. I tell patients they don't actually attack the cancer, but they help your immune system attack the cancer by blocking certain signals that can sort of inhibit your immune system from attacking the cancer. So, that's now a standard treatment for mesothelioma when it's not able to be treated with surgery.

Dr. John Leonard: (Host) So, you've described a number of new approaches. Before we wrap up, I want to get a sense of both what you're most excited about as to promising treatments that patients dealing with lung cancers need to keep on their radar. And also, what are some of your plans and projects here at Weill Cornell that are moving the field forward that you're also very interested in as promising new directions?

Dr. Ashish Saxena: So, I think for lung cancer, as for many cancers, the most exciting thing recently has been this advent of immunotherapy, which as I mentioned involves giving drugs which block certain inhibiting signals that keep the immune system from attacking the cancer.

For lung cancer, it's really been a type of cancer that's been very heavily involved in the studies with immunotherapy. Initially, this was again started out as treatment for advanced lung cancers when they've already spread to stage IV. At this point, most of the time if you're not getting a targeted therapy, an immunotherapy is going to be part of your treatment for advanced lung cancer. But immunotherapy has been shown to improve survival in both the non-small cell and small cell lung cancers in advanced stages where they're already spread and metastatic. But more recently, we've found that they can also help in earlier stages. So in the patients that have non-small cell lung cancer who get radiation and chemotherapy, adding immunotherapy to that improves survival. And even more recently, we've found that for certain patients giving immunotherapy after surgery in certain situations will improve survival, and the most recent is giving immunotherapy with chemotherapy before surgery. That's been shown to have response rates that are very high. About 24% of patients in certain studies had a complete pathological response. So when they went for surgery and had this chemotherapy and immunotherapy beforehand, they had no tumor left at the time of surgery.

So, those are, I think, some of the really exciting treatments that are going on in lung cancer. Here at Cornell, we've done some studies combining immunotherapy with radiation for non-small cell lung cancer prior to surgery and found really high response rates there. And currently, we're doing a study similar to that in advanced small cell lung cancers that are metastatic, we're combining radiation with some immunotherapy and chemotherapy and seeing if that would also improve survival in patients.

Dr. John Leonard: (Host) Finally, I'm wondering if you could just comment on the value of being taken care of by a multidisciplinary team such as that, that we have at Weill Cornell and NewYork-Presbyterian. It seems like given the varied modalities of treating lung cancer, that having a team that's all working together and has expertise in each of these different areas would be very important to a patient. Is that something you've seen in your experience?

Dr. Ashish Saxena: Yes, absolutely. I think it is really important. And, as you mentioned, we have all different types of providers and experts. From screening, we have a lung cancer screening program here. And if something is found on screening, you would go directly to the appropriate people to do the biopsy, to do a surgery. We all meet every week and have a multidisciplinary tumor board where everybody lends their expertise to come up with the best treatment plan for a patient. And often now that does involve multiple types of providers where I might give the chemotherapy and the immunotherapy, but you need also the surgeon obviously to do an excellent surgery. If surgery's not feasible, the radiation oncologist to do the radiation and plan it properly and use the state-of-the-art equipment like we have here. And then, for the research studies, they're combined with people that are doing the surgery, the radiation, the immunotherapy or chemotherapy. So all of that's very important, in addition to the pathologists and molecular pathologists who run the test to see what type of cancer this is and what mutations may be present, the radiologists who would look and can tell how the tumors are responding or if there's any issue. And also, interventionalists to do the biopsy and certain other treatments such as ablation treatments or local treatments where they can kill a tumor when other modalities might not be feasible.

Dr. John Leonard: (Host) Well, I want to thank you for a great discussion. This has been very helpful and I think we've covered the different dimensions of lung cancer very quickly that make an impact on patients with the disease. So, thanks so much for taking the time to join us today.

Dr. Ashish Saxena: Thank you so much, John.

Dr. John Leonard: (Host) I'd like to invite our audience to download, subscribe, rate, and review CancerCast on Apple Podcasts, Google Podcasts, Spotify, or online at 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 CancerCast, conversations about new developments in medicine, cancer care, and research. I'm Dr. John Leonard. Thanks for tuning in.

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