GRACE :: Lung Cancer

Jared Weiss

Denise Brock

Not Your Father’s Squamous Lung Cancer – Currently Available Treatment Options

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 Presented by the
Global Resource for Advancing Cancer Education
in collaboration with 
UNC Lineberger and the Lung Cancer Initiative of North Carolina
             

 
On Friday, November 4th, 2016, in collaboration with the UNC Lineberger and the Lung Cancer Initiative of North Carolina, GRACE presented ‘Not Your Father’s Squamous Lung Cancer’, webcast live in Chapel Hill, North Carolina.  In this second video of the series, Jared Weiss, MD joins us to discuss currently available treatment options.  

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GRACE Video

Trends in Lung Cancer Demographics and Changes in Histology

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GRACE Cancer Video Library - Lung

GCVL_LU-A02b_Lung_Cancer_Demographics_Trends_Histology_Changes

 

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, details the trends in lung cancer demographics and changes in histology by race and gender.

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I will speak to you today about trends in lung cancer demographics. So the incidence is probably the most important trend that we’ve had over the years, and this is somewhat different by men and women.

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Amongst men you can see that we’ve had a nice decline in cancers of the lung, perhaps not as great as we would like but a very real decline. In contrast, amongst women we had an increase in incidence over the years that has finally leveled off and is beginning to hopefully decline.

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There have been some trends in decreased incidence and [improved] survival — these are usually looked at by five year survival rates and unfortunately because of the high morbidity, high mortality, of lung cancer, these rates have not improved as much as some of the other cancers here, but you can see there has been a real, if small decline. This effect has been more pronounced among whites than amongst other minority groups.

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We have had a change in histology over time — histology is the type of lung cancer. When we’ve spoken in other podcasts about differences in efficacy of drugs by squamous or non-squamous, that’s the histology we’re talking about, the subtype of lung cancer. What we’ve seen over time is that there is a decline in incidence of squamous lung cancer and an increased incidence of adenocarcinoma. People have talked a lot about why this may be true — I think the dominant hypothesis is the advent of filters. Filters have not reduced lung cancer incidence but what they have done is bring the particulate matter further out to the periphery of the lung instead of larger particles that tend to settle more centrally in the lung. I think that’s probably what’s driving this change in incidence of squamous versus non-squamous histology.

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There are some marked racial differences in presentation overall of lung cancer and by histology. The gist of this is that in terms of incidence there is increased incidence amongst black patients as compared to caucasian patients.

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Presentation is also worse in black patients — there is a higher incidence of presentation at advanced stage, of course driving inferior outcomes and this is an important target for intervention.

Finally regardless of race, age and histology, I want to talk briefly about the thing that I hope will most change demographics in the years to come, and that’s screening.

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Screening has the potential to catch lung cancer at an earlier stage and hopefully improve our cure rates regardless of any of the other factors we’ve talked about: histology, stage — well hopefully it’ll migrate the stage — race or gender. I think that when we talk about this in five or ten years, we’re going to be talking about much more favorable changes based on the results of screening, and so I would encourage screening for appropriate populations. We’ve done a number of other presentations on screening on cancerGRACE.org, and I refer you to those for more information.

Thank you.


GRACE Video

Lung Cancer Risk Factors

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GRACE Cancer Video Library - Lung

GCVL_LU-A03_Lung_Cancer_Risk_Factors

 

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.


GRACE Video

Lung Cancer Demographics/Epidemiology

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GRACE Cancer Video Library - Lung

GCVL_LU-A02_Lung_Cancer_Demographics_Epidemiology

 

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the demographics and epidemiology of lung cancer.

 

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

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Lung cancer is just behind heart disease for the leading cause of death amongst Americans.

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Within cancer, lung cancer causes the overwhelming majority of the death.

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For both men and women, lung cancer is the second most incident cancer.

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However because of that highly deadly nature of lung cancer we talked about,

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it actually drives the highest death rate in both men and in women.

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Lung cancer can affect anyone: only 44% of our patients are current smokers, about the similar number have previously smoked and quit, and 10-15% are never smokers. However, given how deadly lung cancer is, this drives nonsmoking lung cancer to be one of the greatest causes of suffering and death amongst cancers.

So just to put this into perspective, I have five month old twin daughters. They will never smoke a day in their lives because they will know that I will kill them if they do. Assuming that’s true, that they never smoke a day in their lives, my daughters are far more likely to die of nonsmoking lung cancer than they are to die of breast cancer.

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Lung cancer can also affect anyone regardless of age. You can see here the spread of lung cancer — you can see that the bulk of presentation is at an older age, our median age of presentation is about 71 years, but you can see if you look at the left side of this table that it actually does have real incidence in younger patients. I have treated 20 and 30 year old patients for lung cancer. It is unfortunately quite real. I thank you for your kind attention.


GRACE Video

Are There Significant Genetic Risks for Lung Cancer?

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GRACE Cancer Video Library - Lung

GCVL_LU-A04_Significant_Genetic_Lung_Cancer_Risks

 

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the genetic risk (or lack thereof) for lung cancer.

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It is my privilege to speak to you today about genetics and lung cancer, a topic that I think gets some confusion at times that I’d like to clear up. As we develop targeted therapies for lung cancer, in addition to making extra work for our medical students to learn this, we get to a very complex view of genetics.

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These are the genetics that are in the cells in the lung; every cell in the body has, in its center, a nucleus, and that nucleus contains DNA. This DNA is the instructions to the cell for how to do all of the work that the cell does. You might imagine an analogy to a computer — imagine that all computers were sold with every software program you might ever use, and then just certain computers activated certain programs, so if you’re an analyst maybe Microsoft Excel is activated, if you’re an artist maybe Adobe Photoshop is activated — that’s kind of what the cells in our body do. They all have genetics, they all have DNA, but certain programs are activated.

The key distinction that I want to talk about is the difference between the DNA in the cells in the lung, and the DNA in your reproductive cells that you can hand on to your children. So when we talk about the genetics of targeted therapy, when we talk about EGFR, ALK, ROS1, all these wonderful genetic changes that are leading to more effective, less toxic targeted therapies for our patients, we’re talking about the genetics in the cell in the lung. We’re talking about the genetics that went bad to transform that once-healthy, useful lung cell, into a cell that instead does all the mischief that is lung cancer.

That’s one kind of genetics. Those kind of genetics you cannot pass on to your children — the cells in the lung, no matter how much they change, there is no risk to children.

In contrast, people worry about heritable genetics when we talk about cancer. These are the cells in your ovaries or in your testes if you’re male, and these are the genes, only these genes, that you receive from your parents and can pass on to your children.

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So these are my daughters: at left this is Betty, and I know she has a little more hair than her smiling sister Dina there, but I’ll tell you they are actually identical twins. They have the same DNA. When my wife and I made them, I donated a sperm, she donated an egg, those came together. We got those genes from our parents, we shared them to make these beautiful twins, but if later in life, before or after I have them, if I develop mutations in my lung, no matter where they come from — from bad luck, from smoking, from asbestos, from whatever they should come from, I cannot pass those on to my children. That is a different kind of genetics.

That’s probably the most important thing I have to share with you, but one of the most common questions I get in my clinic is, “well, are there any heritable factors to lung cancer?” That’s what we’ll spend the rest of our time talking about.

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This is in the realm of epidemiology or big studies of large numbers of people. I’m showing you here the relative risk of getting lung cancer if you have a family member with it. It’s roughly double, so there is some kind of family association here. You might say, “well, is this all smoking,” that you’re smoking, you’re around people who are smoking, and if you look at never-smokers, this effect basically still holds.

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There’s a greater risk in the family of developing lung cancer even if nobody smokes. So you might say, “okay, is there a heritable genetic factor to be talked about?”

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The problem is if you look at spouses, the same effect holds, and most of us aren’t too related to our spouses so it’s hard to argue that there’s genetics going on there. So it’s probably some of each.

In general, lung cancer is one of the cancers least associated with the kind of heritable genetics that can be received from your parents or passed to your children.

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There are a few specific syndromes that do have an association — TP53, xeroderma pigmentosum, retinoblastoma, Bloom’s syndrome, Werner’s syndrome, there’s some new data about a very rare but heritable T790m mutation, and there’s some cool data out there about genetic links to nicotine addiction — that there may be a heritable component to why some people taste that first cigarette and say, “this isn’t so good, not for me,” and other people start craving the next one.

So to summarize, the genetics you pass on to your children are not the same as the genetics we’re talking about when we talk about molecular mutations leading to targeted therapy, and the link with those heritable mutations is extremely, extremely weak in lung cancer. If you have lung cancer, it’s unlikely that your children have a greater risk. The only thing I really have to say about that is that if your children smoke, make them stop.

I thank you.


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