Microsoft PowerPoint - Lung cancer screening 20130810 Abstract []Li R i- Literature Review

Gl b l C St ti tiGl b l C St ti tiGlobal Cancer StatisticsGlobal Cancer Statistics in Year 2000
Incidence Mortality
90 80 70
Lung & BronchusLung & Bronchus
100 10 0
56 55 60
15 16 12 22 22 22
80 70 60 50 40 30
80 70 60 50 40 30
0
CA Cancer J Clin. 2013;63: 11-30
Progress in Lung Cancer Image ScreeningProgress in Lung Cancer Image Screening
ELCAPELCAP II ECLAPECLAP NLSTNLST
Czechoslovakia NELSONNELSON DLCSTDLCST
Mayo ClinicMayo Clinic Sloan-Kettering John Hopkins
DLCSTDLCST ITALUNGITALUNG DANTEDANTE
1980s 1990s 2000s 2010s
Earlier Trials of Lung Cancer ScreenEarlier Trials of Lung Cancer Screen NCI in 1970s conducted 3 studiesNCI in 1970s conducted 3 studies
The Johns Hopkins Lung ProjectThe Johns Hopkins Lung Project The Mayo Lung Project: dual screeningThe Mayo Lung Project: dual screening (CXR+cytology) The Memorial SloanThe Memorial Sloan--Kettering National Lung ProgramKettering National Lung Program 10 000 h k > 45 Y/O f > 5 10,000 men, heavy smokers, > 45 Y/O, for > 5 years
Dual screening: 77% CXR, additional 23% by cytology Cytology (+) only: more SCC better survival Cytology (+) only: more SCC, better survival 5-year survival: 35-55%
Similar study and results in CzechoslovakiaSimilar study and results in CzechoslovakiaSimilar study and results in CzechoslovakiaSimilar study and results in Czechoslovakia No improvement in mortality Not recommended at that time
Am Rev Respir Dis 1984;130: 565-70
l C il C iEarly Lung Cancer DetectionEarly Lung Cancer Detection SqCC ADC LCC SCLC Carcinoid Total
DualDual Screening CXR 33 38 16 12 1 100 Cytology 95 0 5 0 0 100 Both 50 27 10 13 0 10050 27 10 13 0 100 Total 51 27 12 9 1 100
CXR only 21 44 22 13 0 100CXR only 21 44 22 13 0 100 Total 43 32 15 10 < 1 100
Am Rev Respir Dis 1984;130: 565-70
l C il C iEarly Lung Cancer DetectionEarly Lung Cancer Detection
Stage I Stage II Stage III Total
DualDual Screening CXR 47 9 44 100 Cytology 81 6 14 100 Both 23 7 70 10023 7 70 100 Total 51 8 42 100
CXR only 38 8 54 100CXR only 38 8 54 100 Total 47 8 45 100
Am Rev Respir Dis 1984;130: 565-70
Biologic Limitations of ImagesBiologic Limitations of Images Tumor size and cellsTumor size and cells
A 5-mm nodule: 108 cells A 10-mm nodule: 109 cells A 30-mm nodule: 2.7 x 1010 cells Death of tumor burden: 1012 cells
Tumor Doubling TimeTumor Doubling Time S ll i i lS ll i i l Small size primary tumor, early metastasesSmall size primary tumor, early metastases
A 1-cm tumor: shed 3-6 x 106 cells into the blood /day Tumor cells can be found in the peripheral blood and bone marrow ofTumor cells can be found in the peripheral blood and bone marrow of all sizes and stages A 1-2-mm tumor: angiogenesis
Bias of Screening DataBias of Screening Data
L d i bi Lead - time bias
Length - time bias
Time
TimeTime
Tumor onset Symptoms Detectable
Time
Natural death
Control group DiagnosisS/S Patient Natural Control group DiagnosisS/S dies death
Bias of Screening DataBias of Screening Data Lead Lead -- time biastime bias
Longer survival, unchanged mortality Length Length -- time biastime biasgg
Better prognosis group OverdiagnosisOverdiagnosis biasbias OverdiagnosisOverdiagnosis biasbias
Improvement in stage distribution, resection rates, survivalsurvival Disease specific mortality
Th M L C hTh M L C hThe Mayo Lung CohortThe Mayo Lung Cohort
Exclude lead time bias Exclude lead time bias
Exclude lead time bias Exclude lead time biasEXPERIMENT-DETECTED
EXPERIMENT- DETECTED
Strauss, GM. J Clin Oncol 2002;20(8): 1973-1983
Th M L C hTh M L C hThe Mayo Lung CohortThe Mayo Lung Cohort
IntentIntent--toto--treattreat
Exclude length time biasExclude length time bias
Strauss, GM. J Clin Oncol 2002;20(8): 1973-1983
Th M L C hTh M L C hThe Mayo Lung CohortThe Mayo Lung Cohort
SURGICALLY RESECTED 50%50%
2%2%
Effective Early ScreeningEffective Early Screening
There must be a preclinical phase ofThere must be a preclinical phase ofThere must be a preclinical phase of There must be a preclinical phase of the diseasethe disease
Technology to detect the disease in Technology to detect the disease in the preclinical stage must be the preclinical stage must be t e p ec ca stage ust bet e p ec ca stage ust be availableavailable
Enables effective interventions Enables effective interventions when the disease is discoveredwhen the disease is discovered
Effective Early ScreeningEffective Early Screening
Reasonable sensitivity andReasonable sensitivity andReasonable sensitivity and Reasonable sensitivity and specificityspecificity
Reasonable accessibility and costReasonable accessibility and cost
Reasonable associated morbidity of Reasonable associated morbidity of the screening teststhe screening teststhe screening teststhe screening tests
Progress in Lung Cancer Image ScreeningProgress in Lung Cancer Image Screening
PLCOPLCO
ALCA (Japan) Sone, mobile CT Nawa nonsmoker
PLCOPLCO
John Hopkins Nawa, nonsmoker
1980s 1990s 2000s 2010s
Mass Screening with Mobile Spiral CTMass Screening with Mobile Spiral CT
40-74 Y/O, annual CXR Lung CA detection rate
0.48% vs 0.03-0.05% (CT vs CXR)
Commentary Lack of long term outcome reportLack of long term outcome report Low positive predictive value (8.5%) Ab t b i k d kAbout numbers in smokers and nonsmokers
Lancet 1998;351: 1242-1245
The Early Lung Cancer Action ProjectThe Early Lung Cancer Action Project (ELCAP)(ELCAP)(ELCAP)(ELCAP)
::
::
X:118/196 (60%) X:118/196 (60%)
: 23% 7% X
Malignancy 2 7%Malignancy 2 7% vsvs 0 7%0 7%Malignancy 2.7% Malignancy 2.7% vsvs 0.7%0.7%
: 26/27 (96%) ( ELCAP)30/59 (51%) (X M L P j t)(51%) (X Mayo Lung Project)
16% 12% ( 2 6%)2.6%)

Detection Failures in Spiral CTDetection Failures in Spiral CT
Nodule among the shadows of old TB Faint nodule with central high attenuation
I i tt ti j t dj t t Increase in attenuation just adjacent to an axial peripheral pulmonary vessel
Adjacent to a craniocaudal peripheral pulmonary vesselp y
A minute faint nodule
Radiology 1999;212: 61-66
Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year resultsin heavy smokers: 2 year results
Conclusion Pastorino Ugo et al. Lancet 2003; 362:593Lancet 2003; 362:593--597597
Combined use of low-dose spiral CT & selective PET effectively detects early lung cancer Lesions up to 5 mm can be checked again at 12 Lesions up to 5 mm can be checked again at 12 months without major risks of progressionmonths without major risks of progression
Lung Cancer Screening With Helical Computed TomographyWith Helical Computed Tomography in Older Adult Smokers A Decision and Cost-effectiveness Analysis
Conclusion
Mahadevia PJ et al. JAMA 2003; 289(3):313JAMA 2003; 289(3):313--322322
Current uncertainty of benefits Harms from invasive testingHarms from invasive testing High costs associated with screening Di tDi t tt nsum m k tin is n t d is blnsum m k tin is n t d is blDirectDirect--toto--consumer marketing is not advisableconsumer marketing is not advisable
Progress in Lung Cancer Image ScreeningProgress in Lung Cancer Image Screening
PLCOPLCO
ALCA (Japan) Sone, mobile CT Nawa nonsmoker
PLCOPLCO NELSONNELSON DLCSTDLCST ITALUNGITALUNG
1980s 1990s 2000s 2010s
National Lung Screening Trial (NLST)National Lung Screening Trial (NLST)
Main objective: LDCT vs CXR L ifi t litLung cancer specific mortality
Enrollment accrual period A 2002 A il 2004Aug 2002 – April 2004
Study sites S S ( SS)Lung Screening Study (LSS):
10 coordinating sites & 25 satellite sites American College of Radiology Imaging Network (ACRIN):American College of Radiology Imaging Network (ACRIN):
23 sites
Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385
National Lung Screening Trial (NLST)National Lung Screening Trial (NLST)
Criteria for participation A 55 74 Y/OAge: 55-74 Y/O Cigarette smoking: 30 pack-years Former smokers: quit within the past 15 yearsFormer smokers: quit within the past 15 years
Participants: 53,45453,454 participants 90 8% white90.8% white 4.4% African American 1 7% Hispanic/Latino1.7% Hispanic/Latino 2.0% Asian
Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385
National Lung Screening Trial (NLST)National Lung Screening Trial (NLST)
R l f I i i l S i i NLSTR l f I i i l S i i NLSTResults of Initial Screening in NLSTResults of Initial Screening in NLST
NLST, New Engl J Med. 2013;368: 1980-1991
Results of Initial Screening in NLSTResults of Initial Screening in NLST
CT ScreeningCT Screening CXR ScreeningCXR ScreeningCT ScreeningCT Screening CXR ScreeningCXR Screening
CT Negative
CT Positive
Sensitivity Specificity
CXR Negative
CXR Positive
Lung CA 18 270 93.8% 49 136 73.5%
Totally Screened 19118 7191 73.4% 23648 2387 91.3%
% 0 09% 3 75% 0 2% 5 70%% 0.09% 3.75% 0.2% 5.70%
NLST, New Engl J Med. 2013;368: 1980-1991
Results of Initial Screening in NLSTResults of Initial Screening in NLST
St
CT Screening (%)CT Screening (%) CXR Screening (%)CXR Screening (%)
CT Negative CT Positive CXR Negative CXR PositiveStage CT Negative CT Positive CXR Negative CXR Positive
IA 2/18 (11.1) 130/266 (48.9) 6/48 (12.5) 40/133 (30.1)
IB 1/18 (5.6) 25/266 (9.4) 2/48 (4.2) 22/133 (16.5)
IIA 2/18 (11.1) 7/266 (2.6) 0 3/133 (2.3)
IIB 1/18 (5.6) 11/266 (4.1) 2/48 (4.2) 8/133 (6.0)
IIIA 2/18 (11.1) 31/266 (11.7) 8/48 (16.7) 19/133 (14.3)
IIIB 7/18 (38.9) 21/266 (7.9) 12/48 (25.0) 15/133 (11.3)
IV 3/18 (16.7) 41/266 (15.4) 18/48 (37.5) 26/133 (19.5)
NLST, New Engl J Med. 2013;368: 1980-1991
Th N i l L S i T i lTh N i l L S i T i lThe National Lung Screening Trial The National Lung Screening Trial (NLST)(NLST)(NLST)(NLST)
A. Lung Cancer B. Death from Lung Cancerg g
Low-dose CT Chest radiography 309/100,000 P-Y
Low-dose CT Chest radiography
Years since Randomization Years since Randomization
A relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; p=0.004) (to prevent 1 death every 320 LDCT)
N Engl J Med 2011;365:395-409
( , ; p ) ( p y )
N Eng J Med 2011;365:395N Eng J Med 2011;365:395--409409
N Eng J Med 2011;365:395N Eng J Med 2011;365:395--409409
European J Cardio-Thoracic Surgery 2012;42: 420-429
Advances in Lung Cancer ScreeningAdvances in Lung Cancer Screening
Eur Radiol 2012;22: 2076-2084
SemiSemi--automated automated VolumericVolumeric MeasurementMeasurement
Eur Radiol 2012;22: 104-119
J Comput Assist Tomogr 2012;36: 181-186
Volume Doubling Time in Lung CAVolume Doubling Time in Lung CA
Radiology 2012;263(2): 578-583
Risk factors for screening Lung CA without known risk factor
Ethnic consideration Genetic predisposition: EGFR…
Histology (cell type) shifting Central vs peripheral tumors
Cost-effectiveness
Screening offered for heavy smokers, Screening offered for heavy smokers, is is it fair?it fair?is is it fair?it fair?
High Risks and Screening RecommendedHigh Risks and Screening Recommended
Category 1 A 55 74 dAge 55-74 y and 30-pack-year history of smoking and Smoking cessation < 15 ySmoking cessation < 15 y
Category 2B Age 50 y andAge 50 y and 20-pack-year of smoking and One additional risk factor (other than 2nd-hand smoke)One additional risk factor (other than 2 hand smoke)
NCCN Guidelines Version 1.2013
Smoking historySmoking history
Radon exposure
Occupational exposure .
Cancer history
Disease history (COPD or pulmonary fibrosis)
Smoking exposure (second-hand smoke)
NCCN Guidelines Version 1.2013
Selection Criteria for LungSelection Criteria for Lung--Cancer ScreeningCancer Screening
Smoking Intensity and LungSmoking Intensity and Lung--Cancer RiskCancer Risk
N Eng J Med 2013;368:728-36
Tammemagi Lung Cancer Risk Prediction Calculator © Calculator predicting 6-year risk of lung cancer by the Tammemagi (PLCOM2012) mo Version 22FEB13MT Instructions: For the characteristics described in Column A fill in the individual's values in Column BInstructions: For the characteristics described in Column A fill in the individual s values in Column B. Note: Values in columns C to F can be ignored and should not be changed.
Characteristics to be entered Enter Values
Centered or referent group
Age in years 45 62 0.0778868 -1.3240756 1.08
Education (enter the highest level obtained) 1 = less than high school grad; 1 = less than high school grad;
2 = high school grad; 3 = Post high school training; 4 = Some college; 5 = College grad; 6 = Postgraduate/professional.
6 4 -0.0812744 -0.1625488 0.92
Body Mass Index (BMI, weight in kg/height in meters 25 27 -0.0274194 0.0548388 0.97
COPD, emphysema or chronic bronchitis (0=No; 1=Y 1 0 0.3553063 0.3553063 1.43
Personal history of cancer (0=No; 1=Yes) 0 0 0.4589971 0 1.58
Family history of lung cancer (0=No; 1=Yes) 1 0 0.587185 0.587185 1.80
Race/ethnicity
White (referent group) (0=No; 1=Yes) 0 0 0
Black (non-Hispanic) (0=No; 1=Yes) 0 0.3944778 0 1.48
Hispanic (0=No; 1=Yes) 0 -0.7434744 0 0.48
Asian (0=No; 1=Yes) 1 -0.466585 -0.466585 0.63
American Indian/Alaskan Native (0=No; 1=Yes) 0 0 0
Native Hawaiian/Pacific Islander (0=No; 1=Yes) 0 1.027152 0 2.79
Smoking status, 0 = Former-smoker 0 0.2597431 0 1.30 1 = Current-smoker
Average number of cigarettes smoked per day** 2 4.597845839 -1.822606 -8.380061413 nonlinear
Duration smoked (years) 1 27 0.0317321 -0.8250346 1.03
Years ago quit smoking. Enter zero for current smok 15 10 -0.0308572 -0.154286 0.97 Model constant -4.532506 -4.532506
xb = -14.84776731 EXP(xb) = 0 0000EXP(xb) 0.0000
Probability of lung cancer = 0.000
* Reference: Tammemagi et al. Selection Criteria for Lung-Cancer Screening . NEJM. 2013;368(8):728-36. ** Transformation of smoking intensity =(((H_smokdday/10) -1)-0.4021541613) Example: The 6-year risk of lung cancer in a white individual who is 55 years old, has some college education, a BMI of 28, who is a former smoker who quit 15 years ago and smoked on average 20who quit 15 years ago and smoked on average 20 cigarettes per day for 30 years is estimated to be 0.005 or 0.5%. NOTE: This calculator was developed and tested in Microsoft® Excel® for Mac 2011 version 14.0.0.
C i i f LC i i f L C S iC S iCriteria for LungCriteria for Lung--Cancer Screening: Cancer Screening: NLST NLST vsvs PLCOPLCOM2012M2012
Probability of lung cancer: > 1.3455% over 6 years
N Eng J Med 2013;368:728-36
Novel Screening: Novel Screening: Canine Cancer Detection
Eur Respir J. 2011;39(3): 669-676
Integrating Integrating th S iff D ?th S iff D ?the Sniffer Dogs?the Sniffer Dogs?
LDCTLDCT CXRCXR Sniffer dogsSniffer dogsgg
Sensitivity 0.938 (0.906-0.963) 0.735 (0.672-0.798) 0.72 (0.51-0.88)
Specificity 0.734 (0.728-0.739) 0.913 (0.910-0.916) 0.94 (0.87-0.98)
Pos. Pred.V. 0.529 (0.484-0.574) 0.702 (0.640-0.768) 0.75 (0.53-0.91)
Neg. Pred. V. 0.999 (0.998-0.999) 0.998 (0.997-0.998) 0.93 (0.86-0.97)g ( ) ( ) ( )
Effective Doses from Some MedicalEffective Doses from Some MedicalEffective Doses from Some Medical Effective Doses from Some Medical Imaging ExaminationImaging Examination
CA Cancer J Clin. 2012;62: 75-100