1. Slides last updated: October 2013

2. 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 Lung cancer is one of the most common cancers, with 1.6 million new cases per year worldwide 1 Lung cancer is the most common cause of death from cancer, responsible for 18.2% of all cancer deaths 1

3. Rates of lung cancer incidence and mortality differ worldwide 1 55% of new lung cancer cases occur in developing countries Highest lung cancer rates are found in Northern America Lung cancer is the most common cancer in men and the second most common in women Lowest lung cancer rates are found in Middle Africa Lung cancer is the 15 th 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 Africa 806040200 406080 MaleFemale 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

4. Rates of lung cancer incidence differ between men and women 1 Lung Prostate Colorectum Stomach Liver Oesophagus Bladder Non-Hodgkin lymphoma Leukaemia Lip, oral cavity Kidney Pancreas Larynx Brain, nervous system Other pharynx 403020100 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 010203040 ASR (W) rate per 100,00 Incidence Mortality Lung 1092056 948993 Lung 515999 427586 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. Five-year survival trend Survival rates for lung cancer are generally low 1 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/faststats/selections.php, accessed on 15/09/2013.

6. NSCLC (85.3% of lung cancer) Lung Cancer (100%) NSCLC makes up approximately 85% of lung cancer 1 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.

7. The distribution of NSCLC subtypes is changing 1 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

8. Slides last updated: October 2013

9. There are two main types of lung cancer 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.

10. NSCLC (85.3% of lung cancer) 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. NSCLC can be further divided into different sub-types 1

11. NSCLC: Adenocarcinoma Adenocarcinoma Adenocarcinoma lesions are usually peripherally located 2 Most frequent in women and non-smokers 2 Some patients have EGFR/ErbB1 mutations; these patients require a specific diagnosis and treatment approach 3 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.

12. NSCLC: Squamous cell carcinoma Squamous Cell Carcinoma 2 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.

13. 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.

14. NSCLC: Other Other, including Not Otherwise Specified (NOS) or Unknown A classification of NOS or unknown is usually due to ineffective sampling and examination 2 This classification is expected to decline in use due to more accurate biopsies and advances in immunohistochemistry and biomarker testing 2 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.

15. Slides last updated: October 2013

16. Relative contribution of risk factors to lung cancer burden 1. Alberg AJ & Samet JM, Epidemiology of Lung Cancer. Chest 2003; 123:21s-49s 2. 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% Asbestos 3 8-10% Radon exposure 2,3 2% Outdoor air pollution 1 Population attributable risk Impact of exposure likelihood of exposure = 85% Cigarette smoking 1-3 9-15% Occupational exposure to carcinogens 1-3

17. Tobacco use is the most important risk factor 1 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

18. Tobacco blend/filtering may affect distribution of NSCLC subtypes 1 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

19. Exposure to asbestos increases the risk of developing lung cancer, mesothelioma and other non-malignant lung disorders 2 Exposure to asbestos coupled with smoking increases the risk to a greater extent than the separate components added together 2 Radon exposure, especially when combined with tobacco smoking, can lead to increased risk of lung cancer 1 Studies in Europe and USA have found that the risk of lung cancer increased by 8.9% and 11% respectively per 100Bq/m 3 increase in radon gas 1,3 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

20. 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 mortality 3 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 studies 4 1. Hosgood HD, Boffetta P, Greenland S, et al. Environ Health Perspect 2010; 118:1743–1747 2. 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 factor 1,2 Wood burning Coal burning Cooking oil fumes

21. Hereditary factors can play a role 1. Coté ML, Liu M, Bonassi S, et al. European Journal of Cancer 2012;48:1957-1968 2. Pray L. Nature Education 2008;1(1) Having a first-degree relative with lung cancer can be a risk factor for developing the disease 1 There are several genes that are potentially implicated in familial lung cancer, one of which codes for nicotinic acetylcholine receptors 2 Mutations to this receptor could increase lung cancer risk from 14% in smokers overall to 20-23% in smokers with the mutation 2

22. Slides last updated: October 2013

23. 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 illnesses 3  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 symptoms 2

24. Some common NSCLC symptoms 1,2 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.

25. Symptoms of metastatic NSCLC may vary widely Symptoms of metastatic lung cancer may vary widely and often coincide with the site of tumour metastasis 1 Clusters of symptoms or paraneoplastic syndromes can point to a possible lung cancer 1 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.