GRACE :: Lung Cancer

Screening Issues and Controversy

Screening debate, pros and cons

Lung Cancer Screening – Process and Potential Benefits

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Dr. Jed Gorden, Swedish Cancer Institute, reviews the lung cancer screening process, including low-dose CT scanning, smoking cessation, follow-up testing and counseling, and describes the potential benefits.

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Lung cancer screening is a very exciting advance in the field of lung cancer which has come about in the last several years. This is where low-dose CT scans, or “CAT” scans, very high resolution images of the lungs, are used to identify nodules and identify early cancers. The critical thing to know is that this is an advancement that has come about in the last several years due to a tremendous amount of government-funded research looking at the safety and the efficacy of using low-dose CT scans to identify high-risk patients who have lung cancer.

Let’s talk about that for a second: high-risk patients. Patients that qualify for lung cancer screening need to understand certain things, and you’re going to have to participate in a shared decision-making conversation with your team and caregivers. So who qualifies, who is high-risk? The high-risk criteria for lung cancer screening and people who should undergo low-dose CT imaging are patients who are 55 to 80 years old, who smoked for at least 30 pack-years which is one pack of cigarettes a day for 30 years, and are actively smoking or quit within the last 15 years. This is the minimum population who is at risk for lung cancer and meets the criteria to undergo low-dose CT screening.

It’s really important to understand that embarking on lung cancer screening and low-dose CT is a journey and a partnership with your team of professionals in the lung cancer screening center. The reason that I say this is because, number one: no single scan will prove that any individual doesn’t have lung cancer. It is through a partnership and continued surveillance based on specific criteria, and discussions with your team over time that will help minimize any risk of lung cancer.

Why would anyone want to embark on this journey? The data that we have and the reason we’re so excited about lung cancer screening now is that the data suggests that through low-dose CT screening of high-risk individuals that the mortality associated with lung cancer is decreased by 20% and the overall all-cause mortality is decreased by almost 7%. But it’s important to understand that this is done in the confines of a multidisciplinary team with counseling and active participation of patients who continue throughout the program and follow the guidelines that are established through screening.

So let’s talk about each one of these components. We’ve talked about the high-risk, which is the patient that’s involved — let’s talk a little bit more about high-risk. So we know that even within this risk profile are those that are at minimal risk for lung cancer, there are those that are at increased risk. We have an identified population of high-risk patients for lung cancer that we described: 55 to 80 years old, actively smoking or quit within the last 15 years, and smoked for at least 30 pack-years. We know that’s the minimum risk and it’s important for people to understand that at the minimum risk level for lung cancer, it takes almost 5,300 people screened to identify one single cancer. As the risk goes up, age goes up, increasing pack years of smoking goes up, we know that the number of people to screen goes down to about 160 to 170 people in the highest risk groups. Therefore it’s important that we adhere to these rigorous guidelines of only those patients who are at the highest risk, who meet the criteria that was described, to undergo lung cancer screening.

Number two: partnership. No single scan allows people to move forward without being continued in the program. It is a continuum that people need to engage in and a partnership with your professional team.

Number three: smoking cessation. Smoking cessation for those that are still smoking is critical to minimizing the risk for lung cancer. This is a teachable moment. This is an opportunity to partner with your team to identify the ability to quit, potential medications for helping you quit, triggers and counseling. I urge people to take advantage of this and to inquire with their team on how best to approach this process as you engage and move forward in the lung cancer screening arena.

The final thing is counseling. It is important to understand that many people who embark on the journey of lung cancer screening, both those that are in the highest risk group and those that are in the minimum risk group to qualify for lung cancer screening will oftentimes be found with an abnormality or what’s called a pulmonary nodule. A pulmonary nodule is a small abnormality seen on a CT scan. It can be described as a dot or a nodule or an abnormality, all descriptors of the same thing, but the critical thing to understand is that the overwhelming majority of the time, these are not cancer. They are benign, but we only know that through continued surveillance and strict adherence to guidelines on when to follow patients up, when to move to additional testing, and when to move on to invasive testing.

The confidence that you build with your professional team will allow you to move forward through this process with education and without fear, and allow you to move forward and minimize the risk of lung cancer in those patients who are high-risk.


Multiplex Testing for Rare Mutations: What Are the Potential Benefits?

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Dr. Ross Camidge, University of Colorado, discusses the potential benefits as well as the disadvantages of multiplex mutation testing.

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More and more, when people are doing molecular testing on their tumor, they’re not just getting one test and if it’s negative doing another test — that’s called sequential testing, they’re doing lots of tests at the same time — that’s called multiplex testing. There are certain good things about that and certain things which are less than good.

In terms of good things, if you do a whole bunch of tests at the same time, you don’t have as long a delay. If you test sequentially it may take you a while before you get to the positive and if you want to make a decision on your treatment as soon as possible, it’s good to get all the information upfront. Also because when you do the sequential testing, each individual way of preparing the tissue wastes some; multiplex testing is a more efficient use of the tissue, so it reduces the chance that you’re going to need another repeat biopsy.

There’s a certain health economic advantage when you utilize multiplex testing, it is what’s called a noncumulative increase in cost. So to look for ten mutations doesn’t cost as much as ten times looking for one mutation. Maybe it costs two or three times as much, and you can add on extra tests.

Perhaps one of the reasons why we’re most enthused by this idea of multiplex testing is you’re going to find some of these rarer abnormalities. Not just the ALK and the EGFR, but increasingly, there’s a collection of abnormalities which are actionable, sometimes through licensed drugs which are not yet licensed in lung cancer but licensed in other diseases, sometimes because they’re an entry into a specific clinical trial. Examples that spring to mind in lung cancer include RET rearrangements, ROS1 rearrangements, and BRAF mutations.

I said there were a few things which were not good. Perhaps the biggest thing is there are some companies commercially doing this who perhaps are adding too many unnecessary tests, and by that I mean tests that really haven’t got any proven value and they’re using up your tissue, they’re increasing the expense to your insurance firm. Perhaps the other downside is that sometimes you get such a wealth of data, like a data dump, you don’t quite know which one to take to the bank. You get all of this information, there are multiple different mutations, and many of them are not driving the cancer, they’re what are sometimes called passenger mutations, and sometimes that ability to sift through it is pushed back onto you or your doctor. Sometimes there’s an algorithm that will print out, “oh, you’re eligible for this trial, or that trial” and there the issue is, what is their metric for saying there’s good enough data to say, “yes, you should go travel to go on this clinical trial.” Sometimes they have a pretty low bar to get over.

For me the best thing to do is — yes, multiplex testing is a good idea, there are certain companies which are better at this than others, and when you get that information you can’t just assume that everything in it is a meaningful result and you really have to sit down, hopefully with an oncologist who understands this, to go through it.


Lung Cancer Risk Factors

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Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses smoking, asbestos, radon and other risk factors for lung cancer.

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I’m going to speak to you today about lung cancer risk factors.

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Of course we cannot ignore that smoking is the dominant risk factor for lung cancer.

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Eighty-five percent or so of our patients have smoked at some point in their lives. However we cannot ignore as well that 15% of so of our patients have never smoked, and about 45% have long since quit.

What to do with this data? In my opinion, we need to really focus on smoking cessation.

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So at top left you see that smoking cessation at any time is worthwhile. Immediately upon quitting smoking, the lung cancer risk falls. This risk falls over time. Stated another way: it’s worth quitting cigarettes at any time point, but the sooner the better.

This effect on health is not just lung cancer. At the bottom left, you can see other cancer mortality declines because lung cancer is not the only smoking-related cancer. Cardiovascular disease competes with cancer for the leading cause for death in Americans — actually I think it edges it out, and you can see that risk declines with quitting smoking. Again, the sooner the better, and for total mortality, shown at the bottom right, the same effect holds.

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Lung cancer can affect anyone, regardless of age. On the far left of this table you can see that lung cancer can strike very young people — I’ve taken care of some of them. However you can also see in looking at the far right side of this curve that age is a legitimate risk factor. Our median age of presentation is about 71, and so this risk does go up with chronologic age.

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There are other risk factors for lung cancer and we need to spend some time particularly on those that are preventable. Asbestos is an important risk factor. This risk varies by fiber type, it also varies by the nature of the exposure. It turns out that occupational exposure, working in a factory on asbestos is a much greater risk factor than environmental exposure, meaning like having asbestos in the walls of the building you live in or something like that. It’s also worth noting that there’s a strong interaction factor here with smoking. Asbestos is bad, smoking is bad — put them together and you have something truly deadly.

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Radon is another major risk factor and also important because it is preventable. This one has a great difference in incidence by geography, shown here, and it’s important to talk about radon because you can do something about this risk.

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( www.epa.gov/radonwww.ncradon.org )

There are kits that can detect radon in your home, and if it’s found it can be mitigated.

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Cooking fumes are a major risk factor, particularly in developing countries and this risk varies by the type of coal used. It turns out that bituminous coal (I didn’t know that word before making this podcast) is the kind that makes a lot of smoke and this dramatically increases the lung cancer risk. In contrast, cleaner coals like anthracite coal seem to be a bit safer. European studies have shown that diesel exhaust contributes to lung cancer risk, but the relative risk increase is somewhat small.

The best data on radiation comes from Hodgkin’s disease and breast cancer, where radiation to the lung roughly triples the risk of later lung cancer.

In terms of pulmonary diseases like COPD, it’s a little hard to tease apart the component caused by smoking because smoking does cause both these diseases as well as lung cancer and the part caused by the actual pulmonary disease, but these pulmonary diseases are inflammatory and it makes common sense that they probably do increase the lung cancer risk a little bit.

Dietary factors are huge in the public consciousness. If you search the web, if you Google, you would think they were the only risk factor and that you can mitigate your lung cancer risk substantially by diet. In particular there was an idea out there that diets high in fruits and vegetables would lower the lung cancer risk. I wish this were true because this is the kind of diet that also prevents some other cancers and helps prevent cardiovascular morbidity and mortality, but the best data available points out that it’s probably just not true.  There’s also a big idea out there that beta carotene supplementation might decrease the lung cancer risk. The best data out there on this shows that not only does it not help, but it might actually increase the lung cancer risk. Again, these may not be the findings that we were looking for, it may not be consistent with all of the stuff in the popular press, but we have to go where the actual data leads us.

There’s real data out there that combined estrogen and progesterone hormones may increase the lung cancer risk a bit — for those more interested in this, Dr. West did an excellent post on this a few years ago that to my mind is still quite current.

The only other cancers that I treat other than lung cancer are cancers of the head and neck. In the tonsils and the base of the tongue, it is clear now that the human papillomavirus, the same one that can cause genital warts, and its high risk forms cause cervical cancer, can also cause cancers of the tonsil and base of tongue. These viruses can also be found in the upper respiratory passages, so there was an idea that perhaps they’re causing cancer there. It’s an interesting idea, it’s still undergoing further research, but to my mind the best available data on this don’t convince me that it’s actually true.

The final subject is genetics. We’re talking here about heritable genetics, the kind that you receive from your parents and that you can potentially pass on to your children, not the molecular changes that we talk about so often on GRACE. This is actually a rather rare risk factor. Lung cancer is one of the least heritable of the cancers, and if you want more information on this, this will be the subject of another podcast.

I thank you for your attention.


How a Diagnosis of Lung Cancer is Made: The Biopsy

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Dr. Gerard Silvestri, Medical University of South Carolina, describes several procedures used to obtain biopsy tissue in order to diagnose lung cancer.

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When I meet with patients who have a new spot on their lung, I tell them I want to do three things and I do it in lay terms and then describe what that means in medical terms. So I ask the question, what is it — that’s the diagnosis, where is it — that’s the stage, and then what can we do about it — those are the treatment options.

As far as diagnosis is concerned, that means getting a tissue biopsy, and there are a number of ways that we can get tissue from patients’ lungs. One is by numbing up the skin on the chest and doing a needle biopsy through the chest wall and into the spot itself. Another is by a procedure called bronchoscopy. That’s where we take a look down into the lungs, the patient is given sedation medicine, and then we take a biopsy from the inside out. There are a number of other ways, including a surgical biopsy where a patient is asleep in the operating room, and the patient gets a small surgical biopsy of their lesion.

Now sometimes we direct our biopsy outside the chest so that we can make a diagnosis and a stage at the same time. For example, if a patient has a liver lesion on a CT scan, we may choose to numb the skin in the abdomen and do a needle biopsy that way, and that gives us both a diagnosis and a stage at the same time.

It’s critically important to make sure that we get those three things right before we embark on treatment: what is it — diagnosis, where is it — stage, what can we do about it — treatment options.


Potential Advantages, Disadvantages and Limitations of Lung Cancer Screening

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Dr. Gerard Silvestri, Medical University of South Carolina, discusses the benefits and drawbacks of lung cancer screenings.

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Lung cancer screening is something that’s quite new in the United States. In 2010, the data was published on a 50,000 person trial where patients were either randomly allocated to get a CT (CAT) scan of their chest, a low dose radiation CT scan, or a chest x-ray, and the study showed a 20% reduction in lung cancer mortality in the patients who got screened for lung cancer with a CT.

There are a few things that you need to understand about that trial. One, it only included patients between the ages of 55 and 74; two, you had to have smoked at least 30 pack-years — that’s 30 years at a pack a day, or for example, 15 years at two packs a day. So you need to have a certain smoking history and be of a certain age to enter into that trial, and now patients in that age range with that smoking history are eligible to be screened for lung cancer with a yearly CT.

The advantage is that you hope to get the cancer when it’s quite small, and so it can be resected with a surgery, taken out, and that patient will have a better chance of being cured of their cancer because as we get to more advanced stages like when the cancer has spread outside of the chest, the hope for a complete cure is lessened. Early stage cancer, screen-detected cancer, has a better chance for cure.

There are some disadvantages to screening though that people need to be aware of. About one quarter of the time, patients who have a scan will have a spot on their lung, or a nodule, or a lesion it’s sometimes called — a quarter of the time those spots are there, and 96% of the time they’re benign spots, but they still need to be evaluated. Sometimes they’re evaluated just with following up with a CT scan, sometimes they’re evaluated with a biopsy, and even sometimes it requires surgery to get those out. That can cause a lot of anxiety in patients and certainly put them at risk for unnecessary procedures, particularly if you’re taking out something that was going to be benign all along. So that’s some of the disadvantage of being screened for lung cancer.

Also, as folks get older, so when you get up into that 75-77 age range, you also have other comorbidities, other things, other health issues that make it difficult for you to undergo surgery, and so some patients may not want to be screened if they have other health problems that may preclude a long life expectancy.

Overall, screening is being implemented in the United States the same way breast cancer screening was implemented years ago in the United States, and we’re doing it very carefully to make sure the patients are of the appropriate setting. The other thing we’re doing is making sure that if patients are smoking, that they get some smoking cessation as part of their screening endeavor.


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