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Low Dose CT Screening for Lung Cancer

Low Dose CT Screening for Lung Cancer. Danny Ma M.D. Section Chief of CT & MRI Director of Oncological Imaging Department of Radiology St. John Hospital & Medical Center. Lung Cancer. Lung cancer accounts for more deaths than any other cancer in both men and women

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Low Dose CT Screening for Lung Cancer

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  1. Low Dose CT Screening for Lung Cancer Danny Ma M.D. Section Chief of CT & MRI Director of Oncological Imaging Department of Radiology St. John Hospital & Medical Center

  2. Lung Cancer • Lung cancer accounts for more deaths than any other cancer in both men and women • Estimated 228,190 new cases of lung cancer expected in 2013, accounting for 14% of cancer diagnosis • Estimated 159,480 deaths (27% of all cancer deaths) expected in 2013 American Cancer Society. Cancer Facts and Figures 2013. Atlanta: American Cancer Society: 2013

  3. 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

  4. Goal of Screening

  5. Lung Cancer Screening • Randomized trials of screening with the use of chest radiography with or without cytologic analysis of sputum specimens have shown no reduction in lung-cancer mortality • Mayo Lung Project • Prostate, Lung, Colon, and Ovary (PLCO) 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.

  6. Recommendation for CXR Screening • “In patients at risk for developing lung cancer, screening for lung cancer with chest radiograph once or at regular intervals is not recommended” • CXR should still be used for evaluating patients with pulmonary symptoms 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

  7. Recommendation for Sputum Screening • “In patients at risk for developing lung cancer, screening for lung cancer with sputum cytology at regular intervals is not suggested” 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

  8. 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.

  9. CT Screening • Study by Naidich et al determined that a low-dose helical CT technique could be used which allowed for sufficient resolution to detect lung nodules while minimizing patient radiation dose • Study by Karabulut et al showed no statistical difference in the number of nodules detected at standard vslow-dose CT 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. Karabulut, Nevzat, et al. Comparison of low-dose and standard-dose helical CT in the evaluation of pulmonary nodules. Eur Radiol (2002) 12:2764 – 2769. DOI 10.1007/s00330-002-1368-4

  10. LDCT Screening • Low dose CT has been shown to detect more nodules and lung cancers, including early stage lung cancers, than chest radiography • Early Lung Cancer Action Project and other studies • No studies have demonstrated decrease in mortality 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.

  11. 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

  12. 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

  13. 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 4mm • 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

  14. CT vs. CXR CT CXR • 649 cancers after positive screening test • 44 cancers after negative screening test • 367 cancers diagnosed during follow-up after screening • 279 cancers after positive screening test • 137 cancers after negative screening test • 525 cancers diagnosed during follow-up after screening 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

  15. Lung Cancer Stage CT CXR • Stage I 63% • Stage III or IV 29.8% • Stage I 47.6% • Stage III or IV 43.2% 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

  16. First Round of Screening Follow-Up The National Lung Screening Trial Research Team. Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer. N Engl J Med 2013;368:1980-91

  17. Lung Cancer Detection After First Round of Screening The National Lung Screening Trial Research Team. Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer. N Engl J Med 2013;368:1980-91

  18. False Positives • CT 96.4% • CXR 94.5% • Most were due to non calcified granulomas or intrapulmonary lymph nodes • Diagnostic evaluation most often consisted of further imaging and invasive procedures were performed infrequently 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

  19. Incidence of Lung Cancer • Low-dose CT 1060 • CXR group 941 • Lung Cancer Deaths • Low dose CT 356 • CXR 443 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

  20. NLST Summary • Rate of positive screening tests was • 24.2% with low dose CT • 6.9% with radiography • LDCT detected more early stage lung cancers • High rate of false positives • 20% decrease in mortality from lung cancer was observed in the low dose CT group as compared with the radiology group (95% CI, 6.8 to 26.7: P=0.004) 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

  21. 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 • 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

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

  23. Standard Dose 1.25 mm 9mm Spiculated Nodule Low Dose 1.25 mm

  24. Standard Dose 2 mm Lung and Airways Low Dose 2 mm

  25. Standard Dose 1.25 mm Mediastinum Comparison Low Dose 1.25 mm

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

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

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

  29. Why 5mm Sections Instead of Thin Slices (1-1.5mm)? • 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

  30. 1.25 mm Calcified Nodule Thin vs Thick Sections 5 mm

  31. 1.25 mm Calcified Nodule Thin vs Thick Sections 5 mm

  32. Concerns of Low-Dose CT • False positives • Overdiagnosis • 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

  33. High Rate of False Positive Scans LDCT • Average detection rate of nodules is 20% but varied from 3% to 50% in the literature • >90% of nodules will be benign Bach P. et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA. 2012, 307(22):2418-2429

  34. Consequences of False Positives • Leads to patient anxiety • Additional follow up CT and possible invasive procedure • Rate of invasive procedures was low (1-4%) • Complications or death from unnecessary biopsy and surgery • 25% of invasive procedures were done in patients with benign histology • Surgical risks are quite low and appear to predominately involve risks from major lung resection of actual lung cancers • 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

  35. Complications from False Positives • “Complications from invasive diagnostic evaluation procedures were uncommon, with death or severe complications occurring only rarely, particularly among participants who did not have 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

  36. Overdiagnosis 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 overdiagnosis 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

  37. Risk of Radiation

  38. Radiation Dose

  39. Radiation Risk • Average person in US receives effective radiation dose of 3 mSv per year • One low-dose CT (1.5mSv) is less than average annual background radiation received in the US (3 mSv) • However, over many years and multiple CTs the radiation dose significantly increases 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

  40. Radiation Risk • A linear, no-threshold (LNT) dose response relationship is used to describe the relationship between radiation dose and the occurrence of cancer • This dose-response hypothesis suggests that any increase in dose, no matter how small, results in an incremental increase in risk • The LNT hypothesis is accepted by the NRC as a conservative model for determining radiation dose standards, recognizing that the model may over estimate radiation risk United States Nuclear Regulatory Commission

  41. Linear No Threshold (LNT) United States Nuclear Regulatory Commission

  42. Radiation Risk • Data derived from six decades of studying survivors of the atomic bombs dropped on Hiroshima and Nagasaki in 1945 • Evidence of adverse effects of exposure at doses greater than 100 mSv resulting in various incidence of cancer • No direct evidence exists of adverse biological effects in humans from radiation doses less than 100 mSv to individual organs or the whole body United States Nuclear Regulatory Commission

  43. 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

  44. Cost of Low Dose CT • Most not reimbursed by many insurance plans or Medicare • Cost varies $99 - $300 • $250 at St. John Hospital & Medical Center

  45. Cost of Low Dose CT • Cost effectiveness analysis of LDCT for lung cancer screening • $75,000 - $169,000/QALY (quality-adjusted life-years) • More than • Colorectal cancer screening ($13,000-$32,000/QALY) • Breast cancer screening ≥ age 40 ($47,700/QALY) • Further cost effectiveness analysis is still needed 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

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