Andrea McKee, M.D. Chairman Department Radiation Oncology Sophia Gordon Cancer Center Lahey Clinic May 15, 2012

1. Andrea McKee, M.D. Chairman Department Radiation Oncology Sophia Gordon Cancer Center Lahey Clinic May 15, 2012

2. Disclosures • None

3. Outline • Lung Cancer Background • Incidence/Mortality • National Lung Screening Trial (NLST) • National Comprehensive Cancer Network (NCCN) • Lung Cancer Screening at Lahey Clinic • Program Structure • Structured Reporting • LUNG-RADS Classification System • Challenges • Rescue Lung, Rescue Life

4. Lung CancerIncidence/Mortality: US • Number one cause of cancer-related death in the US and World • Kills more women than Breast, Ovarian, and Uterus Cancer Combined 200K new cases/yr  160K deaths/yr

5. Risk Factors?

6. Tobacco Trends • History of tobacco use • <20% in 2006 • 42% in 1965 • Demonization campaign • Higher prevalence • Military (1 in 3) vs (1 in 5) • Less educated • Higher risk • Rescue workers • Occupational exposure

7. Tobacco Trends Competition has been tough - tobacco industry, Hollywood, press Guard against withholding of health care services or advocacy based on social history – slippery slope

8. Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS

9. Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS • 35% of Lung Cancer Diagnosis  Current Smokers • 50% of Lung Cancer Diagnosis  Former Smokers • 15% of Lung Cancer Diagnosis  Never Smokers • Lung Cancer 5-Year Overall Survival Remains Unchanged • 1975  12%, Current  15%

10. Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS • Lung Cancer 5-Year Overall Survival • 1975  12%, Current  15% • Stagnant survival result of absent Secondary Prevention • FORMER SMOKERS cannot benefit from PRIMARY PREVENTION • Secondary Prevention = LUNG SCREENING • LUNG SCREENING  Find disease at early more treatable stage • LUNG SCREENING GOAL  Decrease Mortality not Incidence

11. Lung Cancer ScreeningData to support screening been around awhile • NEJM October 2006 • 31,567 patients baseline screened with low dose CT from 1993-2005 • 484 lung cancers detected (85% clinical stage I) • 10 year survival 92% for those having surgery • 8 patients refusing therapy died within 5 years of diagnosis

12. Lung Cancer TreatmentNSCLC: Unscreened Population NSCLC Stage I, II, IIIA Potential Cure Surgical resection Radiotherapy Chemotherapy Stage IIIB/IV Palliative Goldstraw P, Crowley J, Chansky K, et al. (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714.

13. National Lung Screening TrialResults: Stage Shift

14. Stage IV NSCLC <1% = 5 year OS

15. Incidental Finding on CXR Stage T1BN0 58% 5-year Overall Survival Goldstraw P, Crowley J, Chansky K, et al. (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714.

16. Annals of Internal MedicineOctober 2011 • 62 year-old female with a history of well-controlled hypertension presents for routine follow-up. She is asymptomatic and feels well. She has jogged 3 miles 3 times weekly for years with no recent change in exercise tolerance. She has a 30 pack-year history of tobacco use but quit 10 years ago. Normal physical exam. She read a recent study that found a benefit to screening with LDCT and inquires if this is appropriate for her? • What should you recommend?

17. Secondary PreventionPreclinical Diagnosis: Screening Awareness 5mm nodule 6 month fu diagnostic CT recommended 7mm NSCLC treated with lobectomy and nodal evaluation T1aN0 (screened) What is this patient’s 5-year overall survival?

18. Secondary PreventionPreclinical Diagnosis: Screening Awareness 92% = 5 year OS

19. Secondary PreventionPreclinical Diagnosis: Screening Awareness 85% of patients in screened population have stage I lung cancer Asymptomatic 58% 5-year OS Screening Symptomatic Stage I 92% 10-year OS Stage IV 1% 5-year OS

20. US Cancer Mortality RatesSecondary Prevention U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2010. Available at: www.cdc.gov/uscs.

21. US Cancer Mortality RatesSecondary Prevention PSA Mammography Colonoscopy U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2010. Available at: www.cdc.gov/uscs.

22. National Lung Screening Trial(NLST): 6/29/2011 National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.

23. National Lung Screening TrialDesign Overview • Multicenter Randomized Controlled Trial • Sponsor: NCI Division of Cancer Treatment and Diagnosis • 33 US Screening Centers • NCI Division of Cancer Prevention (LSS) • American College of Radiology Imaging Network (ACRIN) • $300,000,000 +

24. National Lung Screening TrialDesign Overview • 53,456 participants • Enrolled 2002 – 2004 • Ages 55-74 • Greater than 30 pack-year smoking history • Active or quit < 15 years • Exclusions • Metallic implants chest or back • Treatment or evidence of cancer in previous 5 years • History of lung cancer • Prior lung resection except needle biopsy • Home O2 requirement • Symptoms: Hemoptysis, weight loss, treated respiratory infection within past 12 weeks • Chest CT within previous 18 months • Participation in other cancer screening/prevention trial • Unable to lie on back with arms above head National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.

25. National Lung Screening TrialDesign Overview • Treatment Arms: • Low Dose Chest CT (1.5 mSv) • PA Chest Radiograph (0.02 mSv) • Screening Intervals: • T0: Baseline prevalence screen • T1: Year 1 incidence screen • T2: Year 2 incidence screen • Positive Test • Non-calcified nodule greater than 4mm in mean diameter • Other findings suspicious for lung cancer (adenopathy, effusion…) • Workup of positives determined by PCPs not NLST • NLST reading radiologist recommendation available

26. National Lung Screening TrialResults: Mortality • Lung cancer specific mortality • 20% reduction in lung cancer specific mortality • LDCT = 356 deaths, CXR = 443 deaths • Median follow-up 6.5 years • Overall mortality • 6.6% reduction in overall mortality • LDCT = 1877 deaths, CXR = 2000 deaths • Not statistically significant when lung cancer deaths excluded National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.

27. National Lung Screening TrialResults: Other • Lung cancer prevalence: 1% • 1 in 100 at risk patients have cancer • Lung cancer annual incidence: 0.5 – 0.8% • Decrease in # of late stage cancers in CT group vs CXR • Real stage shift not just overdiagnosis • Small cell lung cancer • Not detected at earlier stage • Overrepresented as interval cancers • Number Needed to Screen (NNS) is 320 National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.

28. National Lung Screening TrialResults: Rate of Positive ScreeningsAq • CT (24.2%) > 3x more sensitive than CXR (6.9%) • T0 & T1 Rate: 27-28% • T2 Rate: 16.8% • 2 year stability  benign (Fleischner Guidelines) • Expected rate for ongoing LDCT screening • At least one positive result (3 screens): 39.1% • Significant incidental finding: 7.5% • Not screening everyone – highly selected group (3%) National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.

29. National Lung Screening TrialResults: Positive Workup/Adverse Events • False Positives • Most have noninvasive imaging follow-up • CXR: 14.4% • Chest CT: 49.8% • PET/CT: 8.3% • Invasive diagnostic procedures: 2.6 % • Complication rate: 1.4% • Major complication rate: 0.06% • True Positives • Invasive procedure major complication: 11.2% • Surgical resection mortality: 1%

30. NLSTResults: False Positive Workup/Adverse Events • False Positive Rate: • 20-25%: Chance you will end up with a false positive • ~10-12% for Mammography (“Call back”) • False Discovery Rate (1-PPV): • 96%: Chance if you are positive you do not have cancer • Same as mammography • False Positive Biopsy Rate • 0.4-2.4%: Chance if screened you will have an unnecessary invasive procedure (LDCT) • 7-15%: Chance if you end up having a biopsy it will be negative (mammography).

31. NLST NEJM 6/29/2011 NCCN 10/26/2011 • NLST Summary • 20% lung cancer mortality benefit • 7% overall mortality benefit • 1 in 100 has lung cancer • NNT = 320 • Opportunity to save 30,000 lives/yr • NCCN Considerations • Prolonged debate • Cost to Society • Patient anxiety • Radiation exposure • False positives/informed consent • Operational concerns

32. National Comprehensive Cancer Network (NCCN): 10/26/2011 NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org

33. NCCN RecommendationCategories NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org

34. NCCN RecommendationCategories NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org

35. NCCNHigh-Risk Groups

36. NCCN High-Risk Group 2Risk Factors • Personal Cancer History • Lung, lymphoma, smoking related cancers • Family History Lung Cancer in 1st Degree Relative • Chronic Lung Disease • Emphysema • Pulmonary Fibrosis • Carcinogen Exposure • Arsenic, asbestos, cadmium, chromium, diesel fumes, nickel, radon, silica

37. NCCN GuidelinesSolid or Part Solid Nodules Follow-up NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org

38. Lung Cancer ScreeningRisks and Benefits (NCCN) NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org

39. Overdiagnosis, Survival, Mortality Survival Diagnosis Death

40. Overdiagnosis, Survival, Mortality Survival Mortality Diagnosis Death

41. Lung Cancer Mortality Survival Mortality 365 Death due to lung cancer = 20% 443 Diagnosis Death

42. Overall Mortality Survival Mortality 1877 Death due to any cause across entire group= 6.6% 2000 Diagnosis Death

43. Overall Survival Benefit 7%Adjuvant Therapy Reduces Risk • Breast cancer • ACT chemotherapy • 5 years anti-estrogen therapy • Post-mastectomy RT • Prostate Cancer • Post prostatectomy RT • Head and Neck cancer • Post-operative chemoRT • Cervix Cancer • Post-operative chemoRT • Medical-legal consequences

44. OverdiagnosisDetermine time and cause of death in those patients diagnosed and treated for lung cancer Mortality Diagnosis Death

45. CT Lung Cancer ScreeningMorbidity • Radiation exposure • MDCT resolution allows for dose reduction • LDCT <1mSv, Mammography 0.7mSv 1 mSv 10 mSv

46. Radiation Exposure 10 -30 year latency period to develop secondary malignancies from RT exposure Average age of patients in screening trials is 62

47. LUNG-RADSOverview • Purpose: Establish a standardized quality assurance tool to mirror the tool widely utilized in Mammography (BI-RADS). • Objectives: • Standardize terminology • Organized reporting and assessment structure • Data collection tool to facilitate outcome monitoring

48. LUNG RADS Lung Number Category “S” Category Positive for extra-pulmonary finding not suspicious for lung cancer but requiring clinical follow-up Thyroid mass Aneurysm Kidney Mass • Category 1: Negative (12mo) • Category 2: Negative with benign pulmonary findings (12mo) • Category 3: Positive/likely benign (follow-up per NCCN guidelines) • Category 4: Positive/suspicious for malignancy • Category 5: Known cancer

49. LUNG RADS Lung Number Category “S” Category Positive for extra-pulmonary finding not suspicious for lung cancer but requiring clinical follow-up Thyroid mass Aneurysm Kidney Mass Fracture • Category 1: Negative (12mo) • Category 2: Negative with benign pulmonary findings (12mo) • Category 3: Positive/likely benign (FU per NCCN guidelines) • Category 4: Positive/suspicious for malignancy • Category 5: Known cancer

50. An Actuarial Analysis Shows That Offering Lung Cancer Screening As An Insurance Benefit Would Save Lives At Relatively Low Cost • Cost per life-year saved would be below $19,000 Pyenson et al, Health Affairs 31, No.4 770-779: April 2012