��ࡱ�>�� ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������c� ��^\bjbj�� .lx�[\x�[\^T�������22��������������$��0��������ikkkkkk$��^�����������������������i��i���������`{}�A������^�U�0��.�.��.� H���������������������������������������������������������������������������������������.���������2> p:  [ Music ] Lisa Garvin: Welcome to Cancer Newsline. A podcast series from the University of Texas, MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research. Diagnosis. Treatment and prevention. Providing the latest information on reducing our family's cancer risk. I'm your host, Lisa Garvin. And today we're going to be talking about the incidence of lung cancer in women who have never smoked. And we have three guests in the studio, all women -- fortuitously -- to talk about this subject. We have Dr. Mara Antonoff, who is an assistant professor in thoracic and cardiovascular surgery. Dr. Quinn Wynn, assistant professor in radiation oncology. And Dr. Anne Tsao, who is an associate professor in thoracic head and neck medical oncology. Ladies, it's an interesting subject. I always like to say that I think back in 2007 when Dana Reeve -- who is the wife of a famous actor -- died of lung cancer and had never smoked. I think it brought it to the public consciousness. How does lung cancer happen in people who have never smoked Dr. Tsao? Dr. Tsao: So we now know that there may be genetic mutations. What we call oncogenic drivers that could potentially cause lung cancer in patients. We've been quite successful, for instance, in a subset of lung cancer -- the adenocarcinomas. Identifying these oncogenic drivers in developing drugs that are pills that can target these genetic mutations and control the patient's disease. So we've had remarkable progress over the last five years. Lisa Garvin: Why are we seeing it rising in women? And particularly women who don't smoke? Dr. Tsao: Well I think that our attention has become a lot more prominent in this population. We've always had patients like this. It's just that they were never brought to the forefront because we treated them just like any other lung cancer patient. Now we know that this is a distinct population. We have to do genetic screening on them in order to get them the very best therapies. Lisa Garvin: So if women are getting lung cancer and not smoking, they've got to be wondering, what else is out there besides a genetic mutation that might be causing this? And any one of you can answer, Dr. Antonoff? Dr. Antonoff: That's a difficult question to answer. There are a variety of different exposures that have been posed as possible causes for lung cancer. Although the data to support all these potential causes is not particularly clear. We know that genetic predisposition can impact one's likelihood to get lung cancer. Smoking can certainly impact it. And we know that different groups are at different risk for different reasons. You know, we talked about how women who are never smokers, tend -- or I guess I should say, we tend to see lung cancer in women who are never smokers, more so than men. And that's a fact that we see even more frequently among Asian women. So it's certainly clear that there are other predisposing factors. But we certainly have a lot of work to do in establishing clear data between cause and effect. Lisa Garvin: Because I think women, you know, are saying, you know, hey I'm not a smoker. I'm healthy. How in the heck can I get lung cancer? And it's actually more prevalent than breast cancer among women. So I mean -- Dr. Antonoff: So I think that it's not one answer that could be answer very simplicitly or directly. I think there's a lot of exposures in addition to the mutations that Dr. Tsao eluded to. But there's also different exposures in life. Whether it be exposure to secondhand smoke, you know, radon exposure. Cosmic rays. There's a lot of hypothesis that's been published and discussed. But it's really difficult to really definitively say this is a cause and effect. Because in order to do that you actually have to isolate these patients in a bubble, and follow them through time. And say that this is the cause. It's difficult to complete that study, to really say this is our objective -- our primary objective, and this is the results that we've found. So there's so many different exposures in one, you know, women's lifetime. Lisa Garvin: But you know, only recently has lung screening become widely -- and not really widely available yet. We do do it here at MD Anderson. So there are genetic mutations, but have we identified these markers? Dr. Tsao: So, most certainly. There's been most predominantly EGFR mutations. That's the Epidermal Growth Factor Mutation. There are several EGFR tyrosine kinase inhibitors that work for these patients. Also, EML4 ALK is another chromosome translocation that we can find in our patients. This is -- by the way, all of these mutations can also be found in patients who are former smokers. It's just that they tend to have the predominance within our patients who don't smoke, or haven't smoked in the past. There's also ROS1. B-Raf mutations. RET mutations. And we're learning more and more each day about different genetic drivers. And also finding the therapies that can be effective for them. Lisa Garvin: Are women being diagnosed with lung cancer, being diagnosed any later than men? Typically lung cancers stay diagnosed at Stage 3 or higher. Are we seeing any difference among the female population? Dr. Tsao: So not really a difference between men and women as far as identifying it. Although it's always a shock whenever you find out that you have lung cancer. And unfortunately, because this is an insidious disease, we usually do find the majority of our patients within Stage 4. Because it can be something that creeps up on you. You develop some cough. A little shortness of breath. You think you have a cold. And then you don't realize until several months later, that you actually have a lung cancer. Lisa Garvin: All right, what is kind of the age range that we're seeing in women that are diagnosed with lung cancer? Dr. Tsao: So it does vary. We do see patients all the way in their later 20's, all the way to their 80's. And we do know that in often the cases where they've been never smokers, that they can have identification of these genetic drivers at any age. Lisa Garvin: Mm-hm. And Dr. Antonoff, as a surgeon of course, you'll be seeing quite a few lung cancer patients. Surgery is usually part of most people's treatment regimens. Is the approach different for women in any way? Or is it just pretty typical? Dr. Antonoff: Let me just clarify. I know you suggested that surgery is a part of the treatment for most patients. I should clarify that 75% of patients or thereabouts, present with advanced disease that is not amenable to surgical therapy. For patients with early stage disease, which we would consider typically Stage 1, Stage 2 disease, and sometimes patients with early Stage 3 disease, surgery can be part of the treatment algorithm. Certainly for those patients with early stage disease, surgery is the mainstay of therapy. Oftentimes with patients who have disease somewhere in the middle, they require a treatment algorithm that incorporates surgery as well as radiation, and potentially chemotherapy. Depending on individual patient. With regard to your specific question about how surgery may be different for women, the surgical techniques that we offer for women are essentially the same as what we offer for men. The extent of resection, and the operative approach are things that we consider. And certainly at MD Anderson, we are striving to provide the most innovative operative approaches. And the best ways to provide enhanced recovery after operative resections to care for these patients. I wouldn't say that our operative resections are any different for the women from the men. However, we are striving to provide the best perioperative care for women, understanding that they are uniquely different than men. And in fact, after looking at some recent data, we've found that women who were discharged after undergoing pulmonary resection, had very different complaints than men who were discharged. Just related to small symptoms such as pain control; constipation. Things like this. And it's for this reason that we're aiming to tailor a specific perioperative protocol, and desire to have perioperative education unique to women to help make the experience and the recovery optimized for them. Lisa Garvin: Why do you think that their postop symptoms are different? What's -- what do you think is happening there? Dr. Antonoff: I could certainly speculate, but I think that the biology of women is just a little bit different than men. Their GI systems may respond different to some of the narcotic pain medications we use. Their bodyweight may be different in than the men in terms of some of the anesthetics and the perioperative pain medications. There are a variety of different reasons. And it may even be just that the women are communicating with us differently than the men after they've been discharged. But regardless of what the reason is for their different experiences, we certainly want to optimize their satisfaction and their -- enhance their recovery after their procedures. Lisa Garvin: And Dr. Wynn, here at MD Anderson, we've seen a lot of advances in radiation oncology. Where the beams are being more targeted. Lisa Garvin: Mm-hm. Lisa Garvin: There was less, you know, damage to surrounding tissue. What sort of things are we doing for women with breast -- or with lung cancer? Dr. Wynn: Yes. So we -- here at Anderson, we actually -- we have every advanced technology, and our -- we sort of -- our goal is to tailor patient's treatment -- radiation treatment based on stage as well as, you know, whether it be women or men. But it's really dependent on stage. Because the radiation technique, dose, the modality -- whether it be stereotactic, ablated body radiation therapy, proton therapy, or even intensely modular radiation therapy. It really depends on their stage. For example, for patients with early Stage 1 lung cancer, we've been pretty innovative in terms of advancing, and sort of perfecting this technique of stereotactic ablated body radiation therapy called "Saber" where it -- the early data shows that it's potentially as comparable as surgery in terms of local control. It's this technique of delivering high doses of radiation to a targeted, small, you know, peripheral or even central, small lung cancer. And it's a minimally invasive technique where patients can actually undergo this treatment without having any, you know, undergoing any surgery. Lisa Garvin: I know that proton, that was one of the first areas of focus of our proton therapy center when it opened in 2006. Are we still treating people wit proton therapy? Dr. Wynn: Absolutely. So our proton therapy center opened in 2006. We were the first center in the United States to actually commission addition to passive standing beam and a pencil beam. So it's the ability to deliver intensely modular proton therapy. And we've -- we're probably the largest center to treat most thoracic malignancies with this technique. Lisa Garvin: And where does radiation fit in, in the overall -- is it done by itself? With surgery? Chemo first? Lisa Garvin: I mean where does it fit in, in the regimen? Dr. Wynn: So that's a great question. So it's really specifically tailored towards stage. And patient's performance status. But for early stage radiation, we could treat alone, for Stage 1. With this high dose of radiation, we tend not to combine it with chemotherapy because of the potential toxicity. For more advanced stage, like Stage 3 and even Stage 4, radiation is in combination with chemotherapy. Lisa Garvin: Dr. Tsao, are there different quality of life issues for women who have survived lung cancer? Obviously it's a really tough disease, and it can be hard, you know? But what are the things that women may face specifically? Dr. Tsao: So in the early stage setting, when patients have gone through surgery, or a combined chemo radiation, there are always side effects that they encounter because of their treatment. And women in particular, as mentioned earlier, have different body masses. They react to drugs differently. And so the recovery time can vary. And also perceptions of pain and the ability to get back onto their feet can be problematic. In the Stage 4 setting, where we're trying to turn the lung cancer into a chronic disease, especially in the never smoking women population, where sometimes we find the genetic driver and we're able to give pills. We're able to improve on quality of life over chemotherapy. And that's been demonstrated in large, Phase 3 trials. These new agents, when we can identify the genetic driver, have definitely been documented to be improved symptoms. Improved quality of life. Better responses to the treatment. And, you know, women in particular find that to be very useful. And they're able to get back to a normal life while they're being treated for their lung cancer. Lisa Garvin: So when you're talking about these pills, I always think of Tamoxifen. Which is a pill that you can take to, you know, prevent recurrence of cancer and so forth. Are you looking for something along that vein? Dr. Tsao: So it's like the EGFR mutations. There are EGFR tyrosine kinase inhibitors which come in pills. And so these can be taken on a daily basis. And they can often times control the patient's Stage 4 lung cancer, potentially for a year-and-a-half or more. Often times, if they have a small growth, we're able to use surgery or radiation, and continue them on the pill for a lot longer. In the case of patients who have EML4 ALK there's drugs that are called ALK inhibitors. These are pills that you can take once or twice a day, depending on what drug you're on. And again, this controls their disease often times for a couple of years potentially. And so as we improve our science, and we develop new drugs for our specific genetic mutation populations, I think we'll be more successful at making this a very chronic illness. It's just like diabetes. You have to take a medication every day so you keep your diabetes under control. And if you don't take it, you run into problems. Lisa Garvin: Now are these genetic mutations sporadic? Or are they familial? Are they being passed down? Dr. Tsao: So this is very different than breast cancer. We have not found -- at least in the majority of these lung cancer mutations -- that they are inherited. It is a very different situation. It's not like BRCA1 or 2 in breast cancer. There have been rare, anecdotal reports of familial inheritance of some of these genetic mutations, but that is not common. So usually, this is a sporadic mutation that happens. Lisa Garvin: So if most of these mutations are sporadic, how do you even deal with that? I mean there's no screening. There's nothing that can really be done to find these before they've set off. Dr. Tsao: Yes. Unfortunately right now we don't have any early screening techniques that can pick up who's more likely to have these mutations than not. So we are reactionary in a sense, where patients will develop symptoms. They come in and see their primary care doctor, and they're often found to have a lung cancer mass. And that's how they then come to us. There are a lot of research techniques that are looking at early detection and screening. Unfortunately to date, we don't have anything at this moment. Lisa Garvin: So what are we looking at research-wise? Obviously we're going to be focusing in on tumor markers, and as far as the medical oncology goes, what is ahead of you for women? Especially those who have never smoked? As far as, you know, targeted agents. Immunotherapies or whatever. Dr. Tsao: So the targeted agents, which we've discussed a few of them today, are definitely being expanded. The science moves very quickly now. For instance, we now have drugs that can target the RET mutations and BRAF mutations. And one day hopefully we'll have targeted agents for every mutation that we can identify. Immunotherapies is also an extremely new field that's very exciting. What this essentially does, in very basic terms, is it teaches your own immune system to fight the cancer. And so there are a host of different types of agents -- CTLA4 inhibitors, PD1/PDL1 inhibitors, that are being utilized right now in clinical trials to try to help the patients to fight their own cancer. Now all of this still in lung cancer remains on clinical protocols. We have a large portfolio of this here at MD Anderson. Right now it's open for both men and women. But certainly women who have never smoked before, that don't have a genetic driver, they are definitely ones that we want to include in the immunotherapy trials. Lisa Garvin: And Dr. Antonoff, what sort of surgical advances have we seen? I know there's been a lot of minimally invasive techniques. I know that VATS is practiced, you know, in the thoracic area. Are we able to use these minimally invasive surgeries on lung cancer patients? Dr. Antonoff: Absolutely. As you mentioned, minimally evasive thoracoscopic procedures have been used with increasing prevalence over probably the last decade or so. And certainly we're able to employ those techniques here at MD Anderson. But I think the most important thing is having a wide range of tools in our armamentariums that we can individualize the treatment for every single patient. Not every lung cancer is amenable to minimally invasive procedure. But our goal to provide the least invasive, and most curative procedure for each patient. And we have to often times looks at the imaging; look at the patient's functional status in order to determine what the best procedure might be for that patient. But with regard to the use of thoracoscopic procedures, as well as robotic procedures, we have all of those tools available to us here at MD Anderson. Lisa Garvin: And Dr. Wynn, we of course talked quite a bit about some of the radiation therapies available. Lisa Garvin: But it seems like we're moving evermore towards fewer doses. You know, fewer daily doses, and better targeting of the tumor. Dr. Tsao: So that's actually a very good topic. Because in this whole era of health -- value-base healthcare, I think in terms of at least the [inaudible] oncology, where we generally tend to deliver these patients with standard low-doses, standard fractionation every day. And the idea -- there's a biological reason for that. It's just the idea is that when you deliver low doses, these normal tissues -- the surrounding normal tissues have time to repair. And therefore, potentially minimize a late toxicity. However, more research is being performed in our field, where potentially we can offer moderate doses. And maybe decrease a number of treatments or fractions for these patients. Because it may become just a convenience issue, and in terms of outcome it's equivocal to delivering, you know, someone's radiation course in 6 to 7 weeks. But potentially we can do it in 3 to 4. But that's still -- for lung cancer -- that's still being studied. Because it -- and it very well depends on stage. And you see that very -- in the early stage where we're delivering this high dose of radiation in 3 to 4 days. And the local control is significantly better than standard 6 weeks of radiation. There's a biology behind that too. A biology equivalent of delivering these different dose fractionations. Lisa Garvin: But there's obviously a full arsenal of tools available for treating lung cancer. Lisa Garvin: Now that women are saying, oh my gosh, I can get lung cancer even if I don't smoke. What can they do? There's no screening. What can they do with their primary care provider, or their lifestyle that can either find this early, or perhaps prevent? Dr. Tsao: Right. So unfortunately we don't know yet how to prevent sporadic lung cancer from occurring. But women I think need to take care of themselves. They need to reduce their stress load. They need to eat well. Get lots of rest. Do all of their well woman checks with their primary care physician. Do their screening when they're above the certain ages that they need to do this. And then, you know, essentially be very cognoscente that if they don't feel well. If they start losing weight. They start getting short-of-breath. They begin having a cough. Go in and see your doctor, and make sure that you get evaluated. Lisa Garvin: Well I find it interesting though, that -- at least with my doctor, and other people that I know -- that they do not routinely offer lung x-rays or lung screenings to patients who have never smoked. I mean should people ask for a lung x-ray if they feel they're at risk, or -- Dr. Tsao: So if they've had a productive -- if they've had a cough for over several weeks, that hasn't gone away. That hasn't improved with antibiotics, the standard practice would be to do imaging with a chest x-ray. So they should, definitely, follow up with their physicians if they're not improving with antibiotics. Or if they're losing weight, and having shortness of breath. Those are some clear signs that something's not right. Lisa Garvin: Okay. Great. I that'll do us. Thank you ladies so much for being with us today. Dr. Tsao, Dr. Wynn, Dr, Antonoff: Thank you. Lisa Garvin: If you have any questions about anything you've heard today on Cancer Newsline. Contact Ask MD Anderson at 1-877-MDA-6789. Or online at mdanderson.org/ask [music]. Thank you for listening to this episode of Cancer Newsline.  ; P � � B C L M `ik�����������#$02  ���������    !!!!J%i%�(���������û��û�һ�һ��û�ҳ��ó��ó�ҳ�ҳ�ҳ�ҳ�ҳ��ó��ó�ҥ� h�9�hjP9 h�9�hz1 h�9�hz1 5�h�9�hgV5�h�9�hS?�5� h�9�hgV h�9�hS?� h�9�h*%7h�9�h*%75� h�9�h�� jh�9�h��UmHnHu? 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