1. Lung Cancer Screening David Koh, MD, FCCP March 1, 2014

2. Objectives Define the historical aspects of smoking and its relation to lung cancer Describe the current process of lung cancer screening State the newly recommended guidelines for lung cancer screening Describe the new technology for the screening of lung cancer

4. When did we know?

8. Prevalence of Smoking 1.3 billion smokers globally. 1.3 billion smokers globally 1. 47% of men and 12% of women are smokers worldwide. 47% of men and 12% of women are smokers worldwide. 45 Million adults in the US smoke 2. 45 Million adults in the US smoke 2. 23.5% males, 18.5% females. 23.5% males, 18.5% females. There has been a decline in the percentage of smokers from 42% in 1965 to the 20.8% in 2006. There has been a decline in the percentage of smokers from 42% in 1965 to the 20.8% in 2006. 1. WHO Tobacco Free Initiative. 2004 2.CDC. MMWR 2005

10. Cost of Smoking 157 billion dollars MMWR 2002

11. What is in Smoke? A pack-a-day smoker puffs more than 70,000 times a year. A pack-a-day smoker puffs more than 70,000 times a year. 92-95% of the total weight of mainstream smoke is present in the gas phase. 92-95% of the total weight of mainstream smoke is present in the gas phase. Nitrogen, oxygen, and carbon dioxide account for 85% of smoke’s weight. Nitrogen, oxygen, and carbon dioxide account for 85% of smoke’s weight.

12. Selected Cigarette Smoke Constituents in Particulate Phase SubstanceEffects TarCarcinogen Polynuclear aromatic hydrocarbonsCarcinogen NicotineNeuro stimulant and depressant, addicting PhenolCarcinogen and irritant CresolCarcinogen and irritant  - Naphthylamine Carcinogen N-NitrosonornicotineCarcinogen Benzo-pyreneCarcinogen Trace metals (arsenic, polonium 210)Carcinogen IndoleTumor accelerator Carbazole Tumor accelerator CatecholCarcinogen

13. Selected Cigarette Smoke Constituents in Gas Phase SubstanceEffects Carbon MonoxideImpairs oxygen transport Hydrocyanic acidCiliotoxin and irritant AcetaldehydeCiliotoxin and irritant AcroleinCiliotoxin and irritant AmmoniaCiliotoxin and irritant FormaldehydeCiliotoxin and irritant Oxides of nitrogenCiliotoxin and irritant NitrosaminesCarcinogen HydrazineCarcinogen Vinyl ChlorideCarcinogen

15. Mortality Rates More than 399,000 US deaths annually are attributable to cigarette smoking. More than 399,000 US deaths annually are attributable to cigarette smoking. Every 8 seconds, someone dies from tobacco use. Every 8 seconds, someone dies from tobacco use. 40% of neoplasms are related to tobacco. 40% of neoplasms are related to tobacco. 22% of ischemic heart disease is caused by tobacco. 22% of ischemic heart disease is caused by tobacco. On average, male smokers lose 13.2 years and females lose 14.5 years of life expectancy On average, male smokers lose 13.2 years and females lose 14.5 years of life expectancy CDC. MMWR. 2005

18. Death Rates Lung cancer accounts for 32% of all cancer deaths in men and for 25 % of all cancer deaths in women making lung cancer the leading cause of cancer deaths. Lung cancer accounts for 32% of all cancer deaths in men and for 25 % of all cancer deaths in women making lung cancer the leading cause of cancer deaths. For women, incidence rates dropped for cancers of the breast, colon/rectum, uterus, ovary, cervix, and oral cavity but increased for cancers of the lung, thyroid, pancreas, brain/nervous system, bladder, and kidney, as well as for leukemia, non-Hodgkin lymphoma, and melanoma. For women, incidence rates dropped for cancers of the breast, colon/rectum, uterus, ovary, cervix, and oral cavity but increased for cancers of the lung, thyroid, pancreas, brain/nervous system, bladder, and kidney, as well as for leukemia, non-Hodgkin lymphoma, and melanoma. CDC. MMWR. 2008

19. Death Rates

20. Top 12 States for New Lung Cancer Cases in 2012 1 1. California (18,060) 2. Florida (17,860) 3. Texas (14,810) 4. New York (13,620) 5. Pennsylvania (10,890) 6. Ohio (10,270) 7. Illinois (9,190) 8. Michigan (8,210) 9. North Carolina (7,950) 10. Georgia (6,570) 11. Tennessee (6,140) 12. New Jersey (5,990) 1. 2012, American Cancer Society, Inc., Surveillance Research

21. Local Lung Cancer

22. Local Lung Cancer Rate

24. Reality Then At present lung cancer is recognized late. At present lung cancer is recognized late. Opportunities to improve survival are through earlier detection, accurate diagnosis, accurate localization, and curative therapy. Opportunities to improve survival are through earlier detection, accurate diagnosis, accurate localization, and curative therapy. Carbone, PPNIH Conference Annals of Internal Medicine (1970) 73:1003

25. Reality Now National Lung Screening Trial (NLST): 8-year trial (2002 – 2010) compared low-dose ct screening to chest x-ray 8-year trial (2002 – 2010) compared low-dose ct screening to chest x-ray 53,454 current/former smokers, at high risk for lung cancer 53,454 current/former smokers, at high risk for lung cancer Results Released in November 2010: Those who received LDCT had a 20% lower risk of dying from lung cancer than those who received CXR. 1 Results Released in November 2010: Those who received LDCT had a 20% lower risk of dying from lung cancer than those who received CXR. 1 International Early Lung Cancer Action Program (I-ELCAP): 31,567 current/former smokers, at high risk for lung cancer 31,567 current/former smokers, at high risk for lung cancer 484 were diagnosed with lung cancer, 412 at Stage I 484 were diagnosed with lung cancer, 412 at Stage I Results Published in October 2006: Over 80% of patients who have a lung cancer detected by CT screening can be cured. When the lung cancer is found early, and the patient receives surgical removal right away, the cure rate rises to 92%. 2 Results Published in October 2006: Over 80% of patients who have a lung cancer detected by CT screening can be cured. When the lung cancer is found early, and the patient receives surgical removal right away, the cure rate rises to 92%. 2 International Association for the Study of Lung Cancer (IASLC): “The publication of the NLST trial is a major turning point in lung cancer, which demonstrates the enormous potential of CT screening as an early detection tool, which, in combination with smoking cessation programs, is likely to have a major impact on lung cancer.” “The publication of the NLST trial is a major turning point in lung cancer, which demonstrates the enormous potential of CT screening as an early detection tool, which, in combination with smoking cessation programs, is likely to have a major impact on lung cancer.” - Prof. John K Field, MA, PhD, BDS FRCPath, Chair of IASLC - June 29, 2011 - Prof. John K Field, MA, PhD, BDS FRCPath, Chair of IASLC - June 29, 2011 Sources: 1.NLST Research Team, N Engl J Med 365:395-409, 2011 2.IELCAP Investigators, N Engl J Med 355:1763-1771, 2006

28. What was available CT guided needle biopsy: CT guided needle biopsy: Pneumothorax reates reported anywhere from 10- 60% with average of 25%. Pneumothorax reates reported anywhere from 10- 60% with average of 25%. In Ohno’s study, the lowest occurrences of PTX happened at a rate of 28.4% but a positive diagnosis in 77% when: In Ohno’s study, the lowest occurrences of PTX happened at a rate of 28.4% but a positive diagnosis in 77% when: FEV1 > 70% FEV1 > 70% Single puncture Single puncture Needle path < 4 cm. Needle path < 4 cm. Ohno, Y et al. AJR, AM J Roentgenology, 2003

30. Newer Bronchoscopy Techniques EBUS: Endobronchial ultrasonography: Preferred method for sampling lymph nodes without general anesthesia. EBUS: Endobronchial ultrasonography: Preferred method for sampling lymph nodes without general anesthesia. ENB: Electromagnetic navigational bronchoscopy. Uses GPS to get to peripheral nodule. ENB: Electromagnetic navigational bronchoscopy. Uses GPS to get to peripheral nodule. Reconstruction guided bronchoscopy. Reconstruction guided bronchoscopy.

32. Prior to Navigational Bronchoscopy Difficult to get to peripheral nodules because we were looking at a 2-D image. Difficult to get to peripheral nodules because we were looking at a 2-D image. PTX rates were lower at 4% 1. PTX rates were lower at 4% 1. Positive diagnosis 40 2 -60 3 % Positive diagnosis 40 2 -60 3 % 1.Eberhardt, R et al. Am J Resp Critical Care Medicine. 2007 2.Schenk et al. Chest. 2003 3.Schreiber, G et al. Chest. 2003

33. Now With Navagational Bronchoscopy For difficult cases, the yield was 77% 1. For difficult cases, the yield was 77% 1. Overall, the ENB has an accuracy rate of 89% and a negative predictive value of 79% 2. Overall, the ENB has an accuracy rate of 89% and a negative predictive value of 79% 2. 1.Hogarth. Bronchol Intervent Pulmonal. 2011 2.Minnich, DJ. Abstract at Society of Thoracic Surgeon’s Meeting. 2012

34. Electromagnetic Navigation Bronchoscopy (ENB) Procedure Overview CT-ScanDICOM CDPlanning SoftwarePlanned Pathway FileNavigationBiopsyTreatment

35. Lung Cancer Screening Released in April 2012: “Providing Guidance for Lung Cancer Screening: The ALA Interim Report on Lung Cancer Screening” Released in April 2012: “Providing Guidance for Lung Cancer Screening: The ALA Interim Report on Lung Cancer Screening” Key Points: Key Points: Best way to prevent lung cancer is to never start or quit smoking Best way to prevent lung cancer is to never start or quit smoking Low Dose CT (LDCT) should be recommended for those meeting NLST criteria: Low Dose CT (LDCT) should be recommended for those meeting NLST criteria: Current or former smoker, ages 55-74 Current or former smoker, ages 55-74 Smoking history of at least 30 pack-years Smoking history of at least 30 pack-years Those that smoked in the last 15 years. Those that smoked in the last 15 years. No history of lung cancer No history of lung cancer Individuals should not receive a Chest X-ray (CXR) for lung cancer screening For hospitals offering screening: Individuals should not receive a Chest X-ray (CXR) for lung cancer screening For hospitals offering screening: Ethical policies for advertising and promotion of screening should be set Ethical policies for advertising and promotion of screening should be set Develop educational materials to assist patients in discussions on lung cancer screening Develop educational materials to assist patients in discussions on lung cancer screening Provide screening services with access to a multidisciplinary team that can provide the needed follow-up evaluation of nodules Provide screening services with access to a multidisciplinary team that can provide the needed follow-up evaluation of nodules

36. What does the ACCT recommend?

37. Take Home Message For smokers with a greater than 30 pack years. For smokers with a greater than 30 pack years. Current smokers and former smokers that quit less than 15 years ago. Current smokers and former smokers that quit less than 15 years ago. Age 55-74 years old. Age 55-74 years old. Annual Screening with low-dose CT annually. Annual Screening with low-dose CT annually.

38. What about JAMA Panel of experts from ACS, ACCP, ASCO and NCCN who reviewed 8 Randomized Clinical Trials and 13 Cohort Studies Panel of experts from ACS, ACCP, ASCO and NCCN who reviewed 8 Randomized Clinical Trials and 13 Cohort Studies 20% in each round of screening had a positive result, requiring some degree of follow-up and approximately 1% had lung cancer 20% in each round of screening had a positive result, requiring some degree of follow-up and approximately 1% had lung cancer Screening must be done in a center that has the capabilities to evaluate and management findings with a multidisciplinary team Screening must be done in a center that has the capabilities to evaluate and management findings with a multidisciplinary team Low Dose CT (LDCT) screening appears promising, but is also considered to be in it’s infancy Low Dose CT (LDCT) screening appears promising, but is also considered to be in it’s infancy Quality Improvements measures should be reviewed to determine the “right” group to screen, how often and for how long Quality Improvements measures should be reviewed to determine the “right” group to screen, how often and for how long

41. Risks of Second Hand Smoke 3,423-8,866 deaths from lung cancer. 3,423-8,866 deaths from lung cancer. 22,700-69,600 deaths from cardiac causes. 22,700-69,600 deaths from cardiac causes. SIDS 430 deaths. SIDS 430 deaths. Childhood asthma (new and exacerbations) 202,300. Childhood asthma (new and exacerbations) 202,300. Increases risk of COPD by 55 %2. Increases risk of COPD by 55 %2. Doubles the risk of CVA 3. Doubles the risk of CVA 3. CDC. Surgeon General’s Report. 2006. 2. Eisner, MD. Eviron Health. 2005. 3. Goldstein, LB. Stroke. 2006

42. Conclusions Lung cancer can now be reduced by 20%. Lung cancer can now be reduced by 20%. Cancer screening is the key to lowering deaths due to lung cancer by finding lung cancers at an early stage when lung cancer is still curable. Cancer screening is the key to lowering deaths due to lung cancer by finding lung cancers at an early stage when lung cancer is still curable. Who should be screened? Who should be screened? People from ages 55-74. People from ages 55-74. Greater than 30 pack years of smoking. Greater than 30 pack years of smoking. Smoked within 15 years. Smoked within 15 years. No history of lung cancer. No history of lung cancer. Repeat CT for 3 consecutive years. Repeat CT for 3 consecutive years.