Slides last updated: October 2013

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.

Lung cancer incidence and mortality

Both sexes

Men Women0

5

10

15

20

25

Lung

Stomach

Liver

Colorectal

Female breastM

ort

alit

y (%

of a

ll ca

nce

r ty

pe

s)

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

Rates of lung cancer incidence and mortality differ worldwide1

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

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 Africa80 60 40 20 0 20 40 60 80

Male Female

Incidence

Mortality

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.

Estimated age-standardized rates (World) per 100,000

Rates of lung cancer incidence differ between men and women1

Lung

Prostate

Colorectum

Stomach

Liver

Oesophagus

Bladder

Non-Hodgkin lymphoma

Leukaemia

Lip, oral cavity

Kidney

Pancreas

Larynx

Brain, nervous system

Other pharynx

40 30 20 10 0

ASR (W) rate per 100,00

Breast

Cervix uteri

Colorectum

Lung

Stomach

Corpus uteri

Ovary

Liver

Thyroid

Leukaemia

Non-Hodgkin lymphoma

Oesophagus

Pancreas

Brain, nervous system

Kidney

0 10 20 30 40

ASR (W) rate per 100,00

Incidence

Mortality

Lung

1092056948993

Lung

515999427586

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.

Five-year survival trend

Prostatecancer

Breastcancer

Colo-rectal

cancer

Lungcancer

100

80

60

40

20

0

1975 2004

High unmet medical need

Survival rates for lung cancer are generally low1

Survival rates vary depending on stage at diagnosis. The later the stage of diagnosis the lower the survival rates tend to be.

PE

RC

EN

TAG

E (

%)

1. SEER. Fast Stats Online. 5 year survival by diagnosis. 1975-2004. All races. All ages. Male and Female. Available online: seer.cancer.gov/faststats/selections.php, accessed on 15/09/2013.

NSCLC (85.3% of lung cancer)

Lung Cancer (100%)

NSCLC makes up approximately 85% of lung cancer1

Other NSCLC(20.2% of lung cancer)

Large cell carcinoma(2.6% 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.

The distribution of NSCLC subtypes is changing1

Since the 1980’s, squamous cell carcinomas have become relatively less common

Meanwhile, adenocarcinomas have become relatively more common

1. Devasa S, Bray F, Vizcaino A, et al. Int. J. Cancer 2005: 117, 294–299

The reasons for these changes are unclear, but may be due to changes in the composition and filtering of cigarettes

Slides last updated: October 2013

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.

NSCLC (85.3% of lung cancer)

Lung Cancer (100%)

Other NSCLC(20.2% of lung cancer)

Large cell carcinoma(2.6% 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.

NSCLC can be further divided into different sub-types1

NSCLC: Adenocarcinoma

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

40.1%1

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 2011;2:178‒188.

NSCLC: Squamous cell carcinoma

Squamous Cell Carcinoma2

Squamous Cell Carcinoma lesions are generally centrally located, near bronchi

Tends to spread locally

Closely correlated with smoking

21.4%1

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.

NSCLC: Large cell carcinoma

Large Cell Carcinoma

Comprised of undifferentiated cells 2

Lesions are usually peripherally located but can occur anywhere 2

High tendency to metastasize 2

2.6%1

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.

NSCLC: Other

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

20.2%1

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 2011;117:3416‒3423.

Slides last updated: October 2013

Relative contribution of risk factors to lung cancer burden

1. Alberg AJ & Samet JM, Epidemiology of Lung Cancer. Chest 2003; 123:21s-49s2. American Lung Association. Lung Cancer Fact Sheet. Available online: www.lung.org/lung-disease/lung- cancer/resources/facts-figures/lung-cancer-fact-

sheet.html#Other_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-cancer-risk-factors,

accessed on 15/09/2013

8% Asbestos3

8-10% Radon exposure2,3

2% Outdoor air

pollution1

Populationattributable risk

Impact of

exposure

likelihood of exposure

=

85% Cigarette smoking1-3

9-15%Occupational

exposure to carcinogens1-3

Tobacco use is the most important risk factor1

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

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

Tobacco blend/filtering may affect distribution of NSCLC subtypes1

1. Hoffmann D, Djordjevic MV, & Hoffman I. Preventative Medicine 1997:26, 427–434

lower levels of polynuclear aromatic hydrocarbons…

higher levels of tobacco-specific N-nitrosamines…

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:

…and potentially to decreasing incidence of squamous cell

carcinoma…

…and potentially to increasing incidence of

adenocarcinoma

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

• 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

• 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

Radon and asbestos exposure are also important risk factors

1. Darby S, Hill D Auvinen A et al. BMJ 2005;330:223 2. Erren TC, Jacobsen M & Piekarski C. Epidemiology 1999;10:405–411

3. Krewski D, Lubin JH, Zielinski JM et al. Epidemiology 2005;16:137-145

Other risk factors include indoor air pollution and alcohol

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; 118:1743–17472. Lam WK, White NW & Chan-Yeung MM. Int J Tuberc Lung Dis 2004;8:1045–1057

3. Omenn GS, Goodman GE, Thornquist MD, et al. NEJM 1996;334:1150-1155.4. Bandera EV, Freudenheim JL & Vena JE. Cancer Epidemiol Biomarkers Prev 2001;10:813-821

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

Hereditary factors can play a role

1. Coté ML, Liu M, Bonassi S, et al. European Journal of Cancer 2012;48:1957-19682. Pray L. Nature Education 2008;1(1)

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

Slides last updated: October 2013

NSCLC is most often diagnosed at an advanced stage

Many of the symptoms that do appear with more advanced disease can be mistaken for other illnesses3

Bronchitis Pneumonia Consequences of cigarette smoking

1. 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.

2. WebMD. Lung Cancer Health Center: Lung Cancer Symptoms. Available from: www.webmd.com/lung-cancer/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-symptoms-and-diagnosis-beyond-the-basics,

accessed on 15/09/2013.

Early lung cancer may not cause any symptoms.1 25% of people with lung cancer have no symptoms when lung cancer is diagnosed; the remaining 75% develop some symptoms2

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

Chronic Cough

Worsening Long-Term Cough

Weight Loss

Hoarseness

Haemoptysis

Shortness of Breath

Loss of appetite

Recurrent Bronchitis

Wheezing

Constant Chest Pain

Recurrent Pneumonia

Fatigue

1. 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.

2. Thomas K. Patient information: Lung cancer risks, symptoms, and diagnosis(Beyond the Basics). Available from www.uptodate.com/contents/lung-cancer-risks-symptoms-and-diagnosis-beyond-the-basics,

accessed on 15/09/2013.

Symptoms of metastatic NSCLC may vary widely

Symptoms of metastatic lung cancer may vary widely and often coincide with the site of tumour metastasis1

Clusters of symptoms or paraneoplastic syndromes can point to a possible lung cancer1

Dizziness

Bone pain

Lumps near the surface of the body, (lymph nodes) often in the

neck or above the collarbone

Jaundice

Weakness or numbness of the arms or legs

Headaches

Seizures

Bleeding or blood clots

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