Current Approach to Screening for Lung Cancer. James R Jett M.D.

Transcription

1 Current Approach to Screening for Lung Cancer James R Jett M.D.

2 Potential Conflicts of Interest I am Chief Medical Officer for Oncimmune Ltd (Biomarkers of Cancer) Co-Editor of Lung Cancer Section of UP-TO-DATE

3 Trends in Mortality USA: JAMA 2015;314: Reduction All Cause* 1, % Stroke % Heart Disease % Unintentional Injuries % Cancer % Diabetes % *Age-standardized death rate per 100,000

4 Mortality Trends: Six Leading Causes of Death USA COPD Mortality Increased by 100% 21 (1969) to 42 (2013) Rates decreased since 1999 (APC 0.3%) COPD Is The Third Most Common Cause of Death in the USA JAMA 2015;314:

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6 Deaths Due to Cigarette Smoking (2011) for 12 Smoking-Related Cancers in USA Total Deaths Smoking Attributed Percent Larynx 3,728 2,856 77% Lung 156, ,799 80% Oral Cavity & Pharynx 8,576 4,032 47% Esophagus 14,404 7,307 51% Urinary Bladder 14,997 6,724 45% Total (all 12 cancers) 345, ,805 48% Amer Can Society JAMA, pub online June 15, 2015

7 Cancer Statistics 2015 Lung Cancer New Cases Deaths (no.) Cancer Deaths (%) Men 115,610 86, Women 105,590 (48%) Total 221, ,050 71, American Cancer Society, Cancer Statistics; 2015

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9 Cancer Statistics 2015 k k k k k

10 Cancer Statistics 2015 Primary Site New Cases (no.) Deaths (no.) 5-Year Survival Lung 221, , Colorectal 132,700 49, Breast 234,190 40, Pancreas 48,960 40, Prostate 220,800 27, >99 American Cancer Society, Cancer Statistics; 2015

11 Lung Cancer 228,000 new cases in % will be dead within one year Symptomatic lung cancer is advanced stage disease and not curable

12 Lobar Collapse

13 Lung Cancer at Diagnosis: ,000 new cases Localized 15% Regional 22% Distant 56% Wender et al CA Cancer J Clin 2013

14 Where were We? Screening for Lung Cancer American Cancer Society, NCI, American College of Radiology, US Preventive Service Task Force CP

15 Lung Cancer Risk Predictions: PLCO Incidence Rate of Lung Cancer: per 10,000 Person Years on Control Arm (Intervention) Never Smoker: 2.5 (3.3) Former Smoker: 18.7 (19.3) Current Smoker: 71.4 (79.9) Tammemagi et al. JNCI 2011; 103:

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18 National Lung Cancer Screening Trial (NLST) Smoker Former smoker 30 pk yr Age ,000 PLCO 10,000 ACRIN Randomized Low-dose fast spiral CT CXR Years CP

19 Lung Cancer Mortality: October 2010 ARM Lung Cancer Deaths Lung Cancer Mortality per 100,000 PY Reduction in Lung Cancer Mortality LDCT % CXR

20 Cancers Detected by Round of NLST LDCT CXR T T T

21 True and False Positive Screens Low Dose CT Screen Results T0 T1 T2 Total Positive 7,193 6,902 4,052 Lung Cancer 270 (4%) 168 (2%) 211 (5%) No Lung Cancer 96% 98% 95%

22 Results by Round of Screening NLST LDCT T0 (%) T1(%) T2 (%) Cancers (N) Sensitivity Specificity PPV NPV

23 Predictive Value of LDCT Nodule Size PPV% 4mm mm mm mm mm 29.7 >30mm 41.3 Hilar or Mediastinal Adenopathy 18.5 Negative Predictive Value 99.9% NLST Team. NEJM 2013; 368:

24 Two-Year Probability of Lung Cancer by Nodule Size: NELSON 2-Year Size in mm Probability <4 0.6% 5 to <6 0.9% 6 to <7 0.4% 7 to <8 1.8% P=< to <10 2.9% P=<.001 Horewig et al. Lancet Oncol 2014; Pub online Oct 2

25 Two-Year Probability of Lung Cancer by Nodule Size: NELSON 2-Year Size in mm Probability 8 to <10 2.9% 10 to < % 15 to < % 20 to < % % Horewig et al. Lancet Oncol 2014; Pub online Oct 2

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27 Results of Initial LDCT Screening for Lung Cancer LDCT CXR Lung Cancer (N) 292 (1.1%) 190 (0.7%) Stage I 158 (54%) 170 (37%) Stage IIB/IV 120 (41%) 112 (59%) NLST Team. NEJM 2013; 368:

28 Lung Cancer Stage I NELSON 64% (N Eng J Med) NLST 63%

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30 Lung Cancer Detection Cumulative by Year Years Cancer (CT) (649) 78 (279) 5 approx (900) approx (600) 7 (1060) (941) Cancer (CXR) N Eng J Med 2011; 365:

31 NLST Lung Cancer Stages LDCT 1 st 3 Years Overall Stage IA/B 63% 50% Stage III B/IV 21% 31% N Eng J Med 2011; 365:

32 NELSON: LDCT Screening Test Performance Screen Detected Cancers Stage III/IV 22% (44/196) Small Cell 4% (8/196) Adenocarcinoma 52% (102/196) Interval Cancers 83% (29/35) 20% (7/35) 26% (9/35) Horewig et al. Lancet Oncology 2014; 15:

33 National Lung Cancer Screening Trial 20% Mortality Reduction from Lung Cancer 6.7% All Cause Mortality Reduction 320 Persons Needed to be Screened with LDCT to Prevent One Death NNS to prevent one death was 219 NEJM 2011; 365: AIM 2013; pub 30 July

34 Cost Effectiveness of CT Screening: National Lung Cancer Screening Trial Cost Per Life Year: ICER $52,000 (30k - 106k) Cost per QALF $81,000 (52k - 186k) Black et al. New Eng J Med 2014; 371:

35 NLST Incremental Costs for High-Risk Groups: QALY Overall Study Age: Age: Current Smoker Risk Group: 4 th Quintile Risk Group: 5 th Quintile 81k 48k 54k 43k 32k 52k Black et al. New Eng J Med 2014; 371:

36 Number Need to Screen to Prevent One Death Mammogram Age 40-49: 1,904 Age 50-59: 1,339 Age 60-79: 337 Fecal Occult Blood (5 years): 1,374 Flex Sigmoidoscopy: 871 (PLCO: NEJM 2012; 336:2345) PSA: 1,410 Treat 48 to Prevent One Death

37 Pan-Canada CT Screening Trial Cost Analysis from Canadian Public Payer s Perspective for Resources Used in Screening and Treatment of Lung Cancer Participants Had a 2% or Greater Risk Over Three Years Average Cost per Screened Individual With LDCT Was $453 for Initial 18 Months o Costs Dependent on Detected Nodule Size Cressman et al. J Thorac Oncol 2014;9:

38 Pan-Canada CT Screening Trial Mean Cost of $33,344 Over Two Years for Curative Surgery Cost of Treating Advanced Disease: $47,792 Cressman et al. J Thorac Oncol 2014;9:

39 NLST and Smoking Cessation 48% of Participants Were Current Smokers o NELSON Trial 47% Current Smokers 23.5% of Smokers in NLST With Normal Results Quit Smoking After Three Years Smoking Cessation Was Associated With Screen-Detected Abnormalities Quit Rate Was Highest if Screening Study Was Suspicious for Lung Cancer and Was New or Changed From Previous Screen (OR=0.66) Tammemagi et al. JNCI 2014;dju 084, June 11

40 NLST and Smoking Cessation Odds Ratio of Cessation Normal Screen 1 Suspicious Minor Abnormality Major Abnormality (Not Suspicious) Stable Suspicious Abnormality New Unstable Suspicious (32% Quit) 0.91 (P=.005) 0.81 (P<.001) 0.78 (P<.001) 0.66 (P<.001) Tammemagi et al. JNCI 2014;dju 084, June 11

41 Annual Number of Lung Cancer Deaths Averted Approximately 8.6 million Americans met the NLST criteria for screening in 2010 If CT screening was fully adopted A total of 12,000 lung cancer deaths would be averted each year Ma et al Cancer 2013;119:1381-5

42 USA Population Covered by the NLST Criteria NLST criteria would detect 26.7% of all lung cancers NLST criteria covers 6.2% of the population > age 40 Pinsky and Berg, J Med Screen 2012; 19:

43 Lung Cancer Risk Prediction: PLCO Model Age Education Body Mass Index Family History Lung Cancer History of COPD Race Smoking Status (NS, F, C) Smoking Intensity Smoking Duration Quit Time in Former Smokers Tammemagi et al. NEJM 2013;368:728

44 Spread sheet calculator of Lung Cancer risk and Lung Nodule Risk: Available online

45 Screening and Risk Selection Criteria NLST and PLCOm2012 Six-Year Risk Models Applied to CXR Intervention Arm of PLCO PLCOm2012 Risk of 1.5% was at 65 Percentile of Risk in NLST At risk of 1.5% the lung cancer mortality of CT screening was consistently below the CXR rates Tammemagi et al. PLOS 2014; 11:e

46 Screening and Risk Selection Criteria If PLCOm2012 Risk of 1.5%, as Compared to NLST Criteria, Were Applied to PLCO Intervention Arm (Smokers) 8.8% fewer were selected for screening 12.4% more lung cancers detected Sensitivity increased 80% vs 71% Specificity similar 66% vs 63% Tammemagi et al. PLOS 2014; 11:e

47 Screening and Risk Selection Criteria At PLCOm2012 Risk 1.5% the Number Needed to Screen Was 255 (320 in NLST) In percentile the NNS was % of NLST Screenees Had Risk of <1.5% Tammemagi et al. PLOS 2014; 11:e

48 Screening and Risk Prediction Criteria None of the Never Smokers In The PLCO Intervention Arm Had a Risk of > 1.5% Do Not Screen Never Smokers!!! Tammemagi et al. PLOS 2014;11ie

49 Airflow Limitation and Histology Shift in NLST Cohort w/spirometry Lung Cancer Cases N 18, All COPD 34% 52% No COPD 64% 46% Young, et al. AJRCCM 2015;192:

50 Airflow Limitation and Histology Shift in NLST Two-Fold Increase in Lung Cancer Incidence with COPD Rate ratio 2.15 (P <0.001) COPD Was Also Associated with Significantly Fewer BAC-Related Cancers In Patients with Lung Cancer and No COPD, There Were an Additional 29 Cancers in the CT Arm vs CXR Arm Excess of 30 BAC in the CT Arm Young, et al. AJRCCM 2015;192:

51 Screening for Lung Cancer: US Preventive Services Task Force USPSTF recommends annual screening for lung cancer with LDCT in adults aged 55-80years 30 pack year smoking history and currently smoke or have quit within the past 15 years

52 Screening for Lung Cancer: US Preventive Services Task Force Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative surgery. Grade B Recommendation

53 Smoking Cessation and Screening Modeling Data Estimated That Offering Smoking Cessation With Annual Screening Exams Will Improve Cost Effectiveness By: 20-45% Villanti, et al. PloS one 2013; 8:e71379

54 Teachable Moment An Event or Situation in Which There is Increased Capacity or Desire to Change Screening with LDCT is Thought to Be a Teachable Moment for Smoking Cessation

55 Smoking Abstinence & Lung Cancer Specific Mortality Secondary analysis of the NLST Current smokers had an increased lung cancer specific : (HR ) & all cause mortality (HR ) Former smokers in CXR arm that were abstinent for 7 years had 20% mortality reduction. Tanner et al AJRCCM 2015; Pub Online 26 Oct

56 Smoking Abstinence & Lung Cancer Mortality Tanner et al AJRCCM 2015; Pub Online 26 Oct

57 Smoking Abstinence & Lung Cancer Specific Mortality Maximum benefit was seen with smoking abstinence and LDCT screening at 15 years HR 0.62 ( ) 38% risk reduction in lung cancer specific mortality Tanner et al AJRCCM 2015; Pub Online 26 Oct

58 Category Descriptor ACR LungRADS Category Descriptor Primary Category Incomplete - 0 Negative No nodules & definitely benign nodules 1 Benign Appearance or Behavior Nodules with a very low likelihood of becoming a clinically active cancer due to size or lack of growth 2 Probably benign Suspicious Probably benign finding(s) - short term follow up suggested; includes nodules with a low likelihood of becoming a clinically active cancer Findings for which additional diagnostic testing and/or tissue sampling is recommended 3 4A 4B

59 ACR LungRADS Category Category Descriptor Categor y Findings Management Negative Benign Appearanc e or Behavior No nodules and definitely benign nodules Nodules with a very low likelihood of becoming a clinically active cancer due to size or lack of growth 1 2 no lung nodules nodule(s) with specific calcifications: complete, central, popcorn, concentric rings and fat containing nodules solid nodule(s): < 6 mm new < 4 mm part solid nodule(s): < 6 mm total diameter on baseline screening non solid nodule(s) (GGN): < 20 mm OR 20 mm and unchanged or slowly growing category 3 or 4 nodules unchanged for 3 months Continue annual screening with LDCT in 12 months

60 ACR LungRADS Category Category Descriptor Category Findings Management solid nodule(s): Probably Benign Probably benign finding(s) - short term follow up suggested; includes nodules with a low likelihood of becoming a clinically active cancer 3 OR 6 to < 8 mm at baseline new 4 mm to < 6 mm part solid nodule(s) 6 mm total diameter with solid component < 6 mm OR new < 6 mm total diameter 6 month LDCT non solid nodule(s) (GGN) 20 mm on baseline CT or new

61 ACR LungRADS Category Category Descriptor Category Findings Management Suspiciou s Findings for which additional diagnostic testing and/or tissue sampling is recommended 4A 4B 4X solid nodule(s): 8 to < 15 mm at baseline OR growing < 8 mm OR new 6 to < 8 mm part solid nodule(s: 6 mm with solid component 6 mm to < 8 mm OR with a new or growing < 4 mm solid component endobronchial nodule solid nodule(s) 15 mm OR new or growing, and 8 mm part solid nodule(s) with: a solid component 8 mm OR a new or growing 4 mm solid component Category 3 or 4 nodules with additional features or imaging findings that increases the suspicion of malignancy 3 month LDCT; PET/CT may be used when there is a 8 mm solid component chest CT with or without contrast, PET/CT and/or tissue sampling depending on the *probability of malignancy and comorbidities. PET/CT may be used when there is a 8 mm solid component.

62 Lung-RADS in National Lung Screening Trial BASELINE Lung RADS (%) NLST (%) Sensitivity False Positive PPV NPV Pinsky et al. Ann Int Med, pubonline February 10, 2015

63 Lung-RADS in National Lung Screening Trial AFTER BASELINE Lung-RADS (%) NLST (%) Sensitivity False Positive PPV NPV Pinsky et al. Ann Int Med, pubonline February 10, 2015

64 Lung-RADS in National Lung Screening Trial 25 Missed Cancers at Baseline 12 were GGN < 20mm 13 had solid or part-solid nodule < 6mm 61 Missed Cancers on Subsequent Screening 26 were GGN < 20mm 35 had solid or part-solid pre-existing but non-growing nodules Pinsky et al. Ann Int Med, pubonline February 10, 2015

65 True and False Positive Results & Diagnostic Procedures Missed with Lung-RADS Baseline (%) After Baseline (%) All Missed Cancers 25 (9) 61 (16) 86 (13) False Positive Avoided 3,618 (52) 7,997 (76) 11,615 (66) Invasive Procedures 60 (23) 57 (23) 117 (23) Chest CT Avoided 3,557 (50) 2,150 (45) 5,707 (48) Pinsky et al. Ann Int Med, pubonline February 10, 2015

66 Components Necessary for High Quality Lung Cancer Screening Policy Statement of ACCP & ATS Mazzone et al Chest 2014 doi /chest

67 Components Necessary for High Quality Lung Cancer Screening Who is offered screening How often and for how long How the CT is performed Lung Nodule identification Structured reporting Nodule management algorithms Smoking cessation Patient and Provider education

68 February 5th, 2015 CMS issues final approval for Lung Cancer Screening Lengthy report with details on approved screening program and center requirements

69 Must collect and submit data to CMS Data Type Facility Radiologist Patient Ordering practitioner Demographics Indication Smoking history Scanner/radiation dose 4 more items on outcomes Minimum data elements Identifier NPI Identifier NPI DOB, gender, race/ethnicity LC screening; no symptoms Current, former, yrs quit Manufacture/model/dose

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71 Risk Calculator for Radiation Exposure r/calculator-normal-studies.php.