Low Dose CT Screening for Lung Cancer

1. Low Dose CT Screening for Lung Cancer Danny Ma M.D. Director of Oncological Imaging Department of Radiology St. John Hospital & Medical Center Clinical Assistant Professor of Radiology Wayne State University School of Medicine

2. Lung Cancer • Lung cancer accounts for more deaths than any other cancer in both men and women • Estimated 224,210 new cases of lung cancer expected in 2014, accounting for 13% of cancer diagnosis • Estimated 159,260 deaths (27% of all cancer deaths) expected in 2014 American Cancer Society. Cancer Facts and Figures 2014. Atlanta: American Cancer Society: 2014

3. Lung Cancer • In 1964, the first Surgeon General’s report concluded that tobacco smoke was a cause of lung cancer • Today, smoking is thought to cause up to 80-90% of lung cancers American Lung Assocation. Providing Guidance on Lung Cancer Screening To Patients and Physicians. April 23, 2012.

6. Lack of Effective Screening • Lung cancer has similar incidence as other common cancers • Breast, prostate, colorectal cancers • But causes 3-4 times more deaths due to advanced stage of lung cancer at presentation • Attributed to lack of effective screening which will find cancer at an earlier stage, when more effective treatment is available Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

10. Goal of Screening

11. Lung Cancer Screening • Randomized trials of screening with the use of chest radiography with or without sputum analysis have shown no reduction in lung-cancer mortality • 1970s • Mayo, Memorial Sloan-Kettering, and Johns Hopkins Lung Project • 1990s • Prostate, Lung, Colon, and Ovary (PLCO) • Followed 154,901 participants over 12 years Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

12. CT Screening • Until the 1990s, CT was not considered to be a viable option for lung cancer screening • CT has been in clinical use since the mid 1970s • Dose of the radiation delivered to the patient was considered to be too large for use in asymptomatic individuals • Newer technologies allowed faster scan times with high resolution volumetric imaging in a single breath hold • Helical CT late 1980s • Multidetector CT early 1990s Doria-Rose VP, Szabo E. Screening and prevention of lung cancer. In: Kernstine KH, Reckamp KL, eds. Lung cancer: a multidisciplinary approach to diagnosis and management. New York: Demos Medical Publishing, 2010:53-72.

13. LDCT vs Standard Dose CT Low Dose Standard Dose • mA: 40 (can increase to 80 depend on body habitus) • kV: 100 • Radiation dose: 1.5 mSv • More image noise • Both don’t require IV contrast • mA: 200 (can range from 100-600 depend on body habitus) • kV: 100 • Radiation dose: 8 mSv • Less image noise The National Lung Screening Trial Research Team. The National Lung Screening Trial: Overview and study design. Radiology 2011;258:243-53

14. Standard Dose 1.25 mm 8mm Solid Nodule Low Dose 1.25 mm

15. Standard Dose 1.25 mm Mediastinum Low Dose 1.25 mm

16. Standard Dose 1.25 mm Upper Thorax Low Dose 1.25 mm

17. Standard Dose 1.25 mm Upper Abdomen Low Dose 1.25 mm

18. Low Dose 5 mm Same Raw Data Reconstructed Into 5mm vs 1.25mm Low Dose 1.25 mm

19. Why Thin Slices Instead of 5mm Sections? • 5mm thick sections • Partial volume averaging and slice selection • Calcifications in nodules may be missed which can lead to unnecessary f/u CT which can produce anxiety and extra radiation and cost • Inaccurate measurement of nodule showing increase or decrease • Need 1-1.5mm sections for accurate assessment of nodule consistency Goo, Jin et al. Ground-Glass Nodules on Chest CT as Imaging Biomarkers in the Management of Lung Adenocarcinoma. AJR 2011; 196:533-543

20. 1.25 mm Calcified Nodule Thin vs Thick Sections 5 mm

21. LDCT Screening • Low dose CT is superior to chest radiography in the detection of early stage lung cancers • Single arm studies • Mayo • ELCAP (Early Lung Cancer Action Project) • At the time, no randomized control studies comparing LDCT to CXR or usual care • Impact of LDCT on lung cancer mortality is unknown Kanne, Jeffrey P. Screening for Lung Cancer: What Have We Learned? AJR:202, March 2014 530-534

22. Prevalence of Stage I Lung Cancer in CT Observational Studies The National Lung Screening Trial. Overview and Study Design Radiology: Volume 258: Number 1 – January 2011

23. National Lung Screening Trial (NLST) • National Cancer Institute funded randomized trial in 2002 • Does screening with low-dose CT, as compared with chest radiography, reduce mortality from lung cancer among high-risk persons? The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

24. NLST • August 2002 through April 2004 • 53,454 people at high risk for lung cancer at 33 medical centers were enrolled into 2 arms • Low-dose CT 26,722 • CXR 26,732 • Inclusion criteria • 55-74 years old at time of randomization • Smoker with at least 30 pack year history • If former smoker must have quit within 15 years The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

25. NLST • Participants randomly assigned to undergo 3 annual screenings (T0, T1, and T2) with either low dose CT or single view CXR • Median duration of follow up was 6.5 years • Positive – “Suspicous for” lung cancer • CT: Any noncalcified nodule at least 4 mm • CXR: Any noncalcified nodule or mass The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

27. CT vs. CXR The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

28. LDCT Shifts Stage at Diagnosis from Advanced to Early Disease The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

29. Incidence of Lung Cancer • Low-dose CT 1060 • CXR group 941 • Lung Cancer Deaths • Low dose CT 356 • CXR 443 • 20% Reduction in lung cancer mortality • 6.7% reduction in all-cause mortality The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

30. NLST 20% Decrease in Mortality is Not Supported by European Randomized CT Trials

31. Risks of Low-Dose CT • False positives • Complications of workup • Over-diagnosis • Radiation induced cancer • Cost Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

32. High Rate of False Positive with Majority of Pulmonary Nodules Benign

33. Consequences of False Positives • Although most nodules (>90%) are benign, cannot prospectively accurately determine which nodules are benign vs malignant • Leads to patient anxiety • Additional follow up CT • Possible invasive procedure Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

34. Patel, Vishal et al. A Practical Algorithmic Approach to the Diagnosis and Management of Solitary Pulmonary Nodules. Part 1: Radiological Characteristics and Imaging Modalities. CHEST 2013; 143(3):825-839

35. MacMahon, Heber et al. Guidelines for Management of Small Pulmonary NodulesDetected on CT Scans: A Statement from the Fleischner Society. Radiology 2005: 237:395-400

36. False Positives in the NLST • Most false positives were due to non calcified granulomas or intrapulmonary lymph nodes (confirmed with 2 year imaging stability) • Diagnostic evaluation most often consisted of further imaging and invasive procedures were performed infrequently • More invasive testing were more likely to occur in patients who ultimately received a diagnosis of lung cancer The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

37. NLST Screening Follow Up • 27% of Baseline Screening CT were positive • Further workup • 80% Imaging (CT, PET CT, or CXR) • 4% Bronchoscopy • 4% Surgery (Mediastinoscopy/thoracoscopy, etc) • 2% Percutaneous biopsy • Other procedure The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 2011;365:395-409

38. Complications from Invasive Procedures • Rate of invasive procedures was low (1-4% in several LDCT studies) • 25% of invasive procedures were done in patients with benign histology • NLST was 24% • Surgical risks are quite low and appear to predominately involve risks from major lung resection in patients with lung cancer • In NLST mortality for such resections 1% Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

39. Over-diagnosis Hasegawa M, et al. Growth rate of small lung cancers detected on mass CT screening. Br J Radiol 2000;73:1252-1259 • Detection of cancers that never would have become symptomatic and would not have impacted long-term morbidity or mortality • Most cases of over-diagnosis of lung cancer screening is attributed ground-glass opacities (GGO) which have a long mean volume doubling time • Pure ground glass 813 ± 375 days • Mixed ground glass 457 ± 260 days • Solid nodule 149 ± 125 days

42. Risk of Radiation

44. Radiation Dose

45. Radiation Risk • “Risk of a radiation induced cancer in the NLST is approximately one cancer death in 2,500 screened participants” • In NLST, number needed to screen with low-dose CT to prevent one death from lung cancer was 320 • “Therefore the benefit in preventing lung cancer deaths in NLST is considerably greater than the radiation risk” • At least in older individuals given that radiation-induced cancer typically develops 10-20 years later Detterbeck, Frank et al. Screening for Lung Cancer. Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(suppl):e78S-e92S

46. Cost of Low Dose CT • Cost effectiveness analysis of LDCT for lung cancer screening • $75,000 - $169,000/QALY (Costs per quality-adjusted life-year gained) • More than • Colorectal cancer screening ($13,000-$32,000/QALY) • Breast cancer screening ≥ age 40 ($47,700/QALY) McMahon, Pamela M. et al. Cost-Effectiveness of CT Screening for Lung Cancer in the U.S. J Thorac Oncol. 2011 November; 6(11): 1841-1848

47. Cost of Low Dose CT Hendrick R.E. et al. cMahon, Pamela M. et al. Mammography Screening: A New Estimage of Number Needed to Screen to Prevent One Breast Cancer Death. American Journal of Roentgenology. 2012 March; 198: 723-728 Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, et al, PLCO Project Team. (2012) Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 366:2345-57.

48. Smoking Cessation

49. Smoking Cessation • LDCT screening is not an alternative to smoking cessation • Patients may believe their lung cancer will be caught early so they can continue smoking • Referral to smoking cessation program • Requirement for ACR accredited LDCT screening center • Future cost effectiveness analysis of LDCT will need to include smoking cessation

50. Cost of Low Dose CT • Not reimbursed by many insurance plans or Medicare • Out of pocket cost varies: free to $99 - $300 • Any follow up CT due to abnormality will be covered by insurance • Still need an order from referring physician for LDCT • Ensure proper follow up and counseling