Cancer:

1
Slides last updated October 2013
2
Lung cancer incidence and mortality
Lung cancer is one of the most common cancers,
with 1.6 million new cases per year worldwide1
Lung cancer is the most common cause of death
from cancer, responsible for 18.2 of all cancer
deaths1

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C
   and Parkin DM. GLOBOCAN 2008 v2.0, Cancer
   Incidence and Mortality Worldwide IARC Cancer
   Base No.10 Internet. Lyon, France
   International Agency for Research on Cancer
   2010. Available from http//globocan.iarc.fr,
   accessed on 15/09/2013.

3
Rates of lung cancer incidence and mortality
differ worldwide1
Northern America Central and Eastern Europe More
developed regions Eastern Asia Micronesia Western
Europe Polynesia Northern Europe Southern
Europe Australia/New Zealand World South-Eastern
Asia Less developed regions Caribbean Southern
Africa Western Asia South America Central
America Melanesia Northern Africa South-Central
Asia Eastern Africa Western Africa Middle Africa
55 of new lung cancer cases occur in developing
countries Highest lung cancer rates are found in
Northern AmericaLung cancer is the most common
cancer in men and the second most common in
women Lowest lung cancer rates are found in
Middle AfricaLung cancer is the 15th most common
cancer
Incidence Mortality
Male
Female
80
60
40
20
0
20
40
60
80
Estimated age-standardized rates (World) per
100,000

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C
   and Parkin DM. GLOBOCAN 2008 v2.0, Cancer
   Incidence and Mortality Worldwide IARC Cancer
   Base No.10 Internet. Lyon, France
   International Agency for Research on Cancer
   2010. Available from http//globocan.iarc.fr,
   accessed on 15/09/2013.

4
Rates of lung cancer incidence differ between men
and women1
Ferlay J, Shin HR, Bray F, Forman D, Mathers C
and Parkin DM. GLOBOCAN 2008 v2.0, Cancer
Incidence and Mortality Worldwide IARC Cancer
Base No.10 Internet. Lyon, France
International Agency for Research on Cancer
2010. Available from http//globocan.iarc.fr,
accessed on 15/09/2013.
5
Survival rates for lung cancer are generally low1
Five-year survival trend
Survival rates vary depending on stage at
diagnosis. The later the stage of diagnosis the
lower the survival rates tend to be.
PERCENTAGE ()
1. SEER. Fast Stats Online. 5 year survival by
diagnosis. 1975-2004. All races. All ages. Male
and Female. Available online seer.cancer.gov/fast
stats/selections.php, accessed on 15/09/2013.
6
NSCLC makes up approximately 85 of lung cancer1
Lung Cancer (100)
Other NSCLC (20.2 of lung cancer)
Squamous cell carcinoma (21.4 of lung cancer)
Adenocarcinoma (40.1 of lung cancer)

1. Howlader N, Noone AM, Krapcho M, et al. (eds).
   SEER Cancer Statistics Review, 1975-2010,
   National Cancer Institute. Bethesda,
   MD, http//seer.cancer.gov/csr/1975_2010/, based
   on November 2012 SEER data submission, posted to
   the SEER web site, April 2013, accessed on
   15/09/2013.

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The distribution of NSCLC subtypes is changing1
Since the 1980s, squamous cell carcinomas have
become relatively less common
Meanwhile, adenocarcinomas have become relatively
more common
The reasons for these changes are unclear, but
may be due to changes in the composition and
filtering of cigarettes
1. Devasa S, Bray F, Vizcaino A, et al. Int. J.
Cancer 2005 117, 294299
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Slides last updated October 2013
9
There are two main types of lung cancer1

1. Howlader N, Noone AM, Krapcho M, et al. (eds).
   SEER Cancer Statistics Review, 1975-2010,
   National Cancer Institute. Bethesda,
   MD, http//seer.cancer.gov/csr/1975_2010/, based
   on November 2012 SEER data submission, posted to
   the SEER web site, April 2013, accessed on
   15/09/2013.

10
NSCLC can be further divided into different
sub-types1
Lung Cancer (100)
Other NSCLC (20.2 of lung cancer)
Squamous cell carcinoma (21.4 of lung cancer)
Adenocarcinoma (40.1 of lung cancer)

1. Howlader N, Noone AM, Krapcho M, et al. (eds).
   SEER Cancer Statistics Review, 1975-2010,
   National Cancer Institute. Bethesda,
   MD, http//seer.cancer.gov/csr/1975_2010/, based
   on November 2012 SEER data submission, posted to
   the SEER web site, April 2013, accessed on
   15/09/2013.

11
NSCLC Adenocarcinoma
40.11
Adenocarcinoma Adenocarcinoma lesions are
usually peripherally located2 Most frequent in
women and non-smokers2 Some patients have
EGFR/ErbB1 mutations these patients require a
specific diagnosis and treatment approach3
1. Howlader N, Noone AM, Krapcho M, et al. (eds).
SEER Cancer Statistics Review, 1975-2010,
National Cancer Institute. Bethesda,
MD, http//seer.cancer.gov/csr/1975_2010/, based
on November 2012 SEER data submission, posted to
the SEER web site, April 2013, accessed on
15/09/2013. 2. Heighway J Betticher DC. Atlas
Genet Cytogenet Oncol Haematol. February 2004. 3.
Vijayalakshmi R, et al. Indian J Surg Oncol
20112178?188.
12
NSCLC Squamous cell carcinoma
21.41
Squamous Cell Carcinoma2 Squamous Cell Carcinoma
lesions are generally centrally located, near
bronchi Tends to spread locally Closely
correlated with smoking
1. Howlader N, Noone AM, Krapcho M, et al. (eds).
SEER Cancer Statistics Review, 1975-2010,
National Cancer Institute. Bethesda,
MD, http//seer.cancer.gov/csr/1975_2010/, based
on November 2012 SEER data submission, posted to
the SEER web site, April 2013, accessed on
15/09/2013. 2. Heighway J Betticher DC. Atlas
Genet Cytogenet Oncol Haematol. February 2004.
13
NSCLC Large cell carcinoma
2.61
Large Cell Carcinoma Comprised of
undifferentiated cells 2 Lesions are usually
peripherally located but can occur anywhere
2 High tendency to metastasize 2
1. Howlader N, Noone AM, Krapcho M, et al. (eds).
SEER Cancer Statistics Review, 1975-2010,
National Cancer Institute. Bethesda,
MD, http//seer.cancer.gov/csr/1975_2010/, based
on November 2012 SEER data submission, posted to
the SEER web site, April 2013, accessed on
15/09/2013. 2. Heighway J Betticher DC. Atlas
Genet Cytogenet Oncol Haematol. February 2004.
14
NSCLC Other
20.21
Other, including Not Otherwise Specified (NOS) or
Unknown A classification of NOS or unknown is
usually due to ineffective sampling and
examination2 This classification is expected to
decline in use due to more accurate biopsies and
advances in immunohistochemistry and biomarker
testing2
1. Howlader N, Noone AM, Krapcho M, et al. (eds).
SEER Cancer Statistics Review, 1975-2010,
National Cancer Institute. Bethesda,
MD, http//seer.cancer.gov/csr/1975_2010/, based
on November 2012 SEER data submission, posted to
the SEER web site, April 2013, accessed on
15/09/2013. 2. Righi L, Graziano P, Fornari A, et
al. Cancer 20111173416?3423.
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Slides last updated October 2013
16
Relative contribution of risk factors to lung
cancer burden
9-15 Occupational exposure to
carcinogens1-3
8-10 Radon exposure2,3
85 Cigarette smoking1-3
8 Asbestos3
2 Outdoor air pollution1
Population attributable risk

Impact of exposure
likelihood of exposure
1. Alberg AJ Samet JM, Epidemiology of Lung
Cancer. Chest 2003 12321s-49s 2. American Lung
Association. Lung Cancer Fact Sheet. Available
online www.lung.org/lung-disease/lung-
cancer/resources/facts-figures/lung-cancer-fact-sh
eet.htmlOther_Causes, accessed on 15/09/2013
3. Cancer Research UK. Lung Cancer Risk Factors.
Available online www.cancerresearchuk.org/cancer
-info/cancerstats/types/lung/riskfactors/lung-canc
er-risk-factors, accessed on 15/09/2013
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Tobacco use is the most important risk factor1
Higher rates of smoking are associated with
higher rates of lung cancer. A decrease in the
prevalence of smoking in many countries since the
1950s has led to lower rates of lung cancer
incidence and mortality, albeit with a lag of
several decades.
Trends in Tobacco Use and Lung Cancer Death
Rates in the US

1. American Cancer Society. Cancer Statistics 2013.
   Atlanta American Cancer Society, Inc.

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Tobacco blend/filtering may affect distribution
of NSCLC subtypes1
The advent and increased popularity of filtered
cigarettes has also led to a change in the
distribution of lung cancer subtypes. Filters,
along with newer tobacco blends, give rise to
higher levels of tobacco-specific N-nitrosamines
lower levels of polynuclear aromatic
hydrocarbons
and potentially to increasing incidence of
adenocarcinoma
and potentially to decreasing incidence of
squamous cell carcinoma
Filters also tend to lead smokers to inhale smoke
more deeply and retain smoke in the lungs longer,
delivering higher doses of carcinogens to the
peripheries of the lungs
1. Hoffmann D, Djordjevic MV, Hoffman I.
Preventative Medicine 199726, 427434
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Radon and asbestos exposure are also important
risk factors

• Radon exposure, especially when combined with
  tobacco smoking, can lead to increased risk of
  lung cancer1
• Studies in Europe and USA have found that the
  risk of lung cancer increased by 8.9 and 11
  respectively per 100Bq/m3 increase in radon
  gas1,3

• Exposure to asbestos increases the risk of
  developing lung cancer, mesothelioma and other
  non-malignant lung disorders2
• Exposure to asbestos coupled with smoking
  increases the risk to a greater extent than the
  separate components added together2

1. Darby S, Hill D Auvinen A et al. BMJ
2005330223 2. Erren TC, Jacobsen M Piekarski
C. Epidemiology 199910405411 3. Krewski D,
Lubin JH, Zielinski JM et al. Epidemiology
200516137-145
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Other risk factors include indoor air pollution
and alcohol

• Indoor air pollution is a known lung cancer risk
  factor1,2
• Wood burning
• Coal burning
• Cooking oil fumes

A diet high in fresh, beta-carotene-rich fruit
and vegetables shows some evidence of decreasing
lung cancer risk. However, beta carotene given
as a supplement was shown to increase lung
cancer risk and mortality3
There is evidence that those who consume alcohol
in high amounts (more than three drinks per day)
have increased lung cancer risks, although it is
difficult to control for the confounding effect
of smoking in studies4
1. Hosgood HD, Boffetta P, Greenland S, et al.
Environ Health Perspect 2010 11817431747 2.
Lam WK, White NW Chan-Yeung MM. Int J Tuberc
Lung Dis 2004810451057 3. Omenn GS, Goodman
GE, Thornquist MD, et al. NEJM 19963341150-1155.
4. Bandera EV, Freudenheim JL Vena JE. Cancer
Epidemiol Biomarkers Prev 200110813-821
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Hereditary factors can play a role

• Having a first-degree relative with lung cancer
  can be a risk factor for developing the disease1
• There are several genes that are potentially
  implicated in familial lung cancer, one of which
  codes for nicotinic acetylcholine receptors2
• Mutations to this receptor could increase lung
  cancer risk from 14 in smokers overall to 20-23
  in smokers with the mutation2

1. Coté ML, Liu M, Bonassi S, et al. European
Journal of Cancer 2012481957-1968 2. Pray L.
Nature Education 20081(1)
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Slides last updated October 2013
23
NSCLC is most often diagnosed at an advanced stage

• MedlinePlus Medical Encyclopedia. Lung cancer -
  non-small cell. Available from http//www.nlm.nih.
  gov/medlineplus/ency/article/007194.htm, accessed
  on 15/09/2013.
• WebMD. Lung Cancer Health Center Lung Cancer
  Symptoms. Available from www.webmd.com/lung-cance
  r/lung-cancer-symptoms, accessed on 15/09/2013.
• 3. Thomas K. Patient information Lung cancer
  risks, symptoms, and diagnosis
• (Beyond the Basics). Available from
  www.uptodate.com/contents/lung-cancer-risks-sympto
  ms-and-diagnosis-beyond-the-basics, accessed on
  15/09/2013.

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Some common NSCLC symptoms1,2
Mortality is greatly improved when lung cancer is
diagnosed early.
It is very important to discuss any potential
lung cancer symptoms with a health care provider
Worsening Long-Term Cough
Loss of appetite
Chronic Cough
Recurrent Pneumonia
Hoarseness
Wheezing
Shortness of Breath
Constant Chest Pain
Fatigue
Weight Loss
Haemoptysis
Recurrent Bronchitis
1. MedlinePlus Medical Encyclopedia. Lung cancer
- non-small cell. Available from
http//www.nlm.nih.gov/medlineplus/ency/article/00
7194.htm, accessed on 15/09/2013. 2. Thomas K.
Patient information Lung cancer risks, symptoms,
and diagnosis (Beyond the Basics). Available from
www.uptodate.com/contents/lung-cancer-risks-sympto
ms-and-diagnosis-beyond-the-basics, accessed on
15/09/2013.
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Symptoms of metastatic NSCLC may vary widely
Symptoms of metastatic lung cancer may vary
widely and often coincide with the site of tumour
metastasis1
Dizziness
Seizures
Jaundice
Lumps near the surface of the body, (lymph
nodes) often in the neck or above the collarbone
Headaches
Bone pain
Weakness or numbness of the arms or legs
Bleeding or blood clots
Clusters of symptoms or paraneoplastic syndromes
can point to a possible lung cancer1

1. WebMD. Lung Cancer Health Center Lung Cancer
   Symptoms. Available from www.webmd.com/lung-cance
   r/lung-cancer-symptoms, accessed on 15/09/2013.