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Christine D. Berg, MD

Project Officer, NLST

Former, Chief, Early Detection Research Group

National Cancer Institute

Risk-Based Cancer Screening:

Insights from the NLST

National Lung Screening Trial

National Cancer Institute

T S L N

No conflicts of interest to disclose

The FDA does not have jurisdiction over use of helical CT or CXR

screening for lung cancer as it does for mammography. Takes

act of Congress.

2

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Lecture Objectives

Identify benefits and risks of low-dose helical CT

screening for lung cancer

Current lung cancer screening guidelines

Identify groups in whom to consider screening

Identify groups NOT to screen

Radiologic issues for implementation of screening

Nodule management

Smoking cessation

Lung cancer death rates and counts for men and women aged 30-84 years as observed and for modeled tobacco control scenarios.

Moolgavkar S H et al. JNCI J Natl Cancer Inst 2012;jnci.djs136

© The Author 2012. Published by Oxford University Press.

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Low-Dose Helical CT

Allows entire chest to be surveyed in a single

breathhold

Time: approximately 7 - 15 seconds

Reduces motion artifact

Eliminates respiratory misregistration

Narrower slice thickness

Hourly throughput - 4 patients per hour

Radiation dose one fifth of diagnostic CT

One arm study Subjects enrolled % positive

≥5 mm detection rate

ELCAP US 1.000 9,7 2,7

I-ELCAP International 31.567 13,3 1,3

ALCA Japan 1.611 11,5 0,9

University Munster, Germany 817 18,8 1,5

Shinshu University, Japan 5.483 5,1 0,4

Finnish Institute of Occupational Helth, Finland 602 8,0 0,8

SMC, University School of Medicine, Seoul, Korea 6.406 6,9 0,2

Hitachi Health Care Center, Japan 7.956 6,8 0,5

PALCAD, Ireland 449 24,7 0,4

University of Milano Italy 1.035 5,9 1,1

NY-ELCAP, US 6.295 14,4 1,6

PLuSS, US 3.642 19,5 1,5

COSMOS Italy 5.201 10,7 1,1

University of Navarra, Spain 911 14,4 1,3

Univerity of Turin, Italy 519 22,0 1,0

Totale 73.494 11,6 1,1

media 12,8 1,1

range 5,1-24,7 0,4-1,6

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Survival is not adequate measure of screening benefit

Lead-time bias Earlier detection may prolong survival independent of delay in death

Survival

Sx DX

O

Cancer

CT DX

Lead time

Survival prolongation due to lead time

Prolonged survival with mortality from cause other than

lung cancer or complication of screening

L

Overdiagnosis is an extreme form of length bias

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The National Lung Screening Trial

Definitive RCT for effect of lung cancer screening on

lung cancer specific mortality

NLST design

Prospective, randomized trial comparing low-dose helical CT screening

to chest x-ray screening for three annual screens with the endpoint of

lung cancer specific mortality in 53, 454 high risk participants

Eligibility

Age 55-74; asymptomatic current or former smoker; 30 pack year

smoking history; former smokers: quit within preceding 15 years

Parameters 90% power to detect 20% difference in lung cancer mortality; α = 0.05

Median follow-up for outcomes ~ 6.5 years (Maximum: 7.4)

Vital status known for 97% LDCT | 96% CXR

http://radiology.rsna.org/content/early/2010/10/28/radiol.10091808.full

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Baseline Characteristics by Trial Arm and

Comparison with US Census Data for High-risk Population

CT

N (%)

CXR

N (%)

US Census*

(%)

Male 15,769 (59) 15,761 (59) (58)

Age at baseline (years)

< 59

60-64

65-69

> 70

11,441 (43)

8,171 (31)

4,756 (18)

2,354 (9)

11,425 (43)

8,197 (31)

4,762 (18)

2,348 (9)

(35)

(29)

(20)

(15)

Race/Ethnicity

Black

Hispanic

1,195 (4)

479 (2)

1,181 (4)

456 (2)

(6)

(2)

Smoking status at baseline

Former smoker

Current smoker

13,857 (52)

12,865 (48)

13,827 (52)

12,905 (48)

(43)

(57)

*Percentages were calculated using data from respondents to the US Census Tobacco Use Supplement of the Continuing

Population Survey (2002-2004) who met NLST age and smoking eligibility criteria.

Interim analysis: lung cancer mortality 10-20-2010

Arm Person

Years (py)

Lung

cancer

deaths

Lung cancer

mortality per

100,000 py

Reduction in

lung cancer

mortality (%)

Value of

test

statistic

Efficacy

boundary

LDCT 144,102.6 356 247 20.0 –3.2 –2.033

CXR 143,367.5 443 309

Deficit of lung cancer deaths in CT arm exceeds that expected by chance,

even allowing for multiple looks at the data.

CXR arm compared with matched 30,000 cohort in PLCO, no benefit of

CXR seen.

p = 0.0041

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Kaplan-Meier curves for lung cancer and all-cause mortality

1.00

0.99

0.98

0.97

0.96

0.95

0.94

0.93

0.92

0.91

0.90

0 1 2 3 4 5 6 7 8

Years from randomization

Pro

bab

ility

of

surv

ival

: A

LL

par

tici

pan

ts

CT arm lung cancer

CXR arm lung cancer

CT arm all-cause

CXR arm all-cause

Lung cancer case survival Kaplan Meier curve CXR compared with matched group in PLCO and no difference

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 1 2 3 4 5 6 7

Pro

bab

ility

of

surv

ival

: P

arti

cip

ants

wit

h lu

ng

can

cer

Years from diagnosis CT arm

CXR arm

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Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Table 5. Results for National Lung Screening Trial Subset.

Oken, M. M. et al. JAMA 2011;306:1865-1873

Copyright restrictions may apply.

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Screen positivity rate by screening round & arm

Low-dose helical CT CXR

Number

screened

Number

positive

%

Positive

Number

screened

Number

positive

% Positive

Screen 1 26,314 7,193 27.3 26,049 2,387 9.2

Screen 2 24,718 6,902 27.9 24,097 1,482 6.2

Screen 3 24,104 4,054 16.8** 23,353 1,175 5.0**

All screens 75,136 18,149 24.2 73,499 5,044 6.9

* Positive screen: nodule ≥ 4 mm or other findings potentially related to lung cancer.

** Abnormality stable for 3 rounds could be called negative by protocol.

True and false positive screens

Screening

Result

Low-dose Helical CT CXR

Screen 1

N (%)

Round 2

N (%)

Round 3

N (%)

Round 1

N (%)

Round 2

N (%)

Round 3

N (%)

Total Positives

Lung cancer

No lung cancer

7,193 (100)

270 (4)

6,923 (96)

6,902 (100)

168 (2)

6,734 (98)

4,054 (100)

211 (5)

3,843 (95)

2,387 (100)

136 (6)

2,251 (94)

1,482 (100)

65 (4)

1,417 (96)

1,175 (100)

78 (7)

1,097 (93)

Data reflect the final interpretation, including benefit of historical comparison exams.

Positive Screens were > 3-fold higher in the LDCT arm

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lung cancers diagnosed in NLST

Screen Result and Time Period CT (%) CXR (%)

Total T0-T2 Screen [+] lung cancers 649 (61.2%) 279 (29.6%)

Total T0-T2 Screen [-] lung cancers 44 (4.2%) 137 (14.6%)

Total NO screen lung cancers 367 (34.6%) 525 (55.8%)

Total lung cancers in arm 1060 (100.0%) 941 (100%)

892 NO screen cancers include: post-screen time period (N = 802)

never screened (N= 35) | due for screen (N = 55)

NLST Investigators; NEJM 2011

Definitions of Performance Measures

Sensitivity: probability of a positive test given that the patient is ill

# of true positives / # of true positives + # of false negatives

Specificity Probability of a negative test given that the patient is well

# of true negatives / # of true negatives + # of false positives

Negative Predictive Value # of true negatives / # of true negatives + number of false

negatives

Positive Predictive Value # of true positives / # of true positives + # of false positives

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Performance Characteristics at T0

Sensitivity LDCT: 93.8% (270/288)

CXR: 73.5% (136/185)

Specificity LDCT: 73.4% (19,043/25,954)

CXR: 91.3% (23,5477/25,790)

Negative Predictive Value LDCT: 99.9% CXR: 99.8%

Positive Predictive Value (PPV1) LDCT: 3.8% (267/7,010)

CXR: 5.7% (136/2,379)

PPV for positive finding that led to biopsy (PPV3) LDCT: 52.9% (265/501)

CXR: 70.2% (132/188)

Follow-up of Positive Screens by

Screening Round and Trial Arm

CT CXR

Round 1

N (%)

Round 2

N (%)

Round 3

N (%)

Round 1

N (%)

Round 2

N (%)

Round 3

N (%)

Total Positives with documented

follow-up

Imaging procedures

Clinical procedures

Other procedures

No procedures

7,051 (100)

5,718 (81)

5,086 (72)

219 (3)

680 (10)

6,741 (100)

2,517 (37)

3,190 (47)

130 (2)

2,876 (43)

3,911 (100)

2,009 (51)

2,151 (55)

102 (3)

1,389 (36)

2,348 (100)

2,009 (86)

1,413 (60)

72 (3)

173 (7)

1,456 (100)

968 (67)

723 (50)

36 (2)

378 (26)

1,149 (100)

906 (79)

658 (57)

42 (4)

192 (17)

Biopsy procedures

Cytology procedures

Resection

Total Invasive/Lung cancers

240 (3)

248 (4)

249 (4)

737/270

144 (2)

109 (2)

169 (2)

422/168

146 (4)

125 (3)

193 (5)

464/211

121 (5)

88 (4)

106 (4)

315/136

48 (3)

59 (4)

48 (3)

155/65

62 (5)

63 (6)

54 (5)

179/78

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Histopathological Type by

Trial Arm and Stage at Diagnosis*

*Table includes diagnosed cancers with data on both stage and histopathological type.

CT CXR

I

N (%)

II

N (%)

III

N (%)

IV

N (%)

Total

N (%)

I

N (%)

II

N (%)

III

N (%)

IV

N (%)

Total

N (%)

Adenocarcinoma 217

(58.5)

27

(7.3)

62

(16.7)

65

(17.5)

371

(100)

121

(38.2)

29

(9.1)

56

(17.7)

111

(35.0)

317

(100)

Squamous cell

carcinoma

122

(51.5)

25

(10.5)

58

(24.5)

32

(13.5)

237

(100)

72

(37.5)

22

(11.5)

51

(26.6)

47

(24.5)

192

(100)

Bronchiolo-alveolar

carcinoma

88

(81.5)

4

(3.7)

10

(9.3)

6

(5.6)

108

(100)

18

(51.4)

3

(8.6)

8

(22.9)

6

(17.1)

35

(100)

Large cell carcinoma 21

(51.2)

3

(7.3)

12

(29.3)

5

(12.2)

41

(100)

14

(33.3)

2

(4.8)

17

(40.5)

9

(21.4)

42

(100)

Small cell carcinoma 6

(5.0)

7

(5.8)

42

(34.7)

66

(54.5)

121

(100)

12

(8.6)

8

(5.8)

42

(30.2)

77

(55.4)

139

(100)

Other 55

(40.7)

7

(5.2)

32

(23.7)

41

(30.4)

135

(100)

35

(21.2)

9

(5.5)

48

(29.1)

73

(44.2)

165

(100)

Total 509

(50.2)

73

(7.2)

216

(21.3)

215

(21.2)

1,013

(100)

272

(30.6)

73

(8.2)

222

(24.9)

323

(36.3)

890

(100)

screening-related complications

CT lung cancer

CT NO cancer

CXR lung cancer

CXR No cancer

N % N % N % N %

Positive screens 649 100 17,053 100 279 100 4,674 100

Major complication 75 11.6 12 0.1 24 8.6 4 < 0.1

Death 60 days after invasive procedure 10 1.5 6 < 0.1 10 3.8 0 0

Overall complications were low.

Complications in patients with no cancer diagnosis were minimal.

The 20 types of major complication included hemothorax requiring

tube placement, myocardial infarction, bronchopulmonary fistula

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Radiation Risk

LDCT Comparison to Standard Chest CT

Acceptable chest CT screening can be accomplished at a small fraction of the dose of a standard chest CT

NLST Effective Dose vs Standard Chest CT

1.4 1.6 1.62.1

2.4

7.0

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

EURO GROUP CTEXPO & ICRP 60 CTEXPO & ICRP 103 STD CHEST CT

mSv

male female std chest ct

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radiation dose

Whole body effective dose (weighted average dose to each organ) Low dose helical CT: 1.5mGy

Mammogram: 0.7mGy

CXR: 0.01 mGy

Low dose helical CT: estimates of organ specific dose Lung: 4 mGy

Breast: 4 mGy

Red bone marrow, stomach, liver and pancreas: each ~1 mGy

Screening mammogram organ specific dose: Breast : 4mGy

Other organs: < 0.1mGy

CXR: effective dose ~ 0.1 mSv

http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray

Radiation Risks vs Benefits

• 3 screens Smokers Age 55 - 57

• Radiation risk from screens

– 1-3 lung cancer deaths per 10,000 screened

– 0.3 breast cancers per 10,000 females screened

• Radiation risk from follow-up CT scans

– Low-dose or thin-section chest CT + 25%

– Diagnostic chest CT + 100%

• Cumulative mortality reduction NLST

– 30 lung cancer deaths per 10,000 screened

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Change in cancer risk per 10,000 screened

(assuming 20% mortality reduction)

Berrington de Gonzalez A, Kim KP, Berg CD. J Med Screen 2008;15:153-158.

Female never smokers

-4

-2

0

2

4

6

8

10

Age 30-32 Age 40-42 Age 50-52 Age 60-62

Lung cancer risk

Lung cancer benefit

Breast cancer risk

Screening Result Odds Ratios (95% CI; p-values)

Normal – no abnormalities (Referent group) 1.00

Negative for lung cancer, minor other abnormalities 0.85 (0.72-0.99; p = 0.037)

Negative for lung cancer, significant other

abnormalities

0.68 (0.52-0.89; p = 0.004)

Positive for lung cancer 0.46 (0.37-0.57; p < 0.001)

Positive for lung cancer, stable, no significant change

from previous screen

0.67 (0.52-0.87; p = 0.003)

Odds ratios from multivariable* longitudinal logistic analysis for being a current smoker given the previous screening result.

NLST LSS Study of Factors Associated with Smoking Behavior

Conclusion: The probability of subsequent smoking is inversely

associated with the abnormality of screening result in a dose-response

fashion. Tammemagi, M and Taylor K

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European Randomized Trials

NELSON DLCST LUSI DANTE ITALUNG MILD UKLS‡

No. of rounds 4 5 5 5 4 10 or 5 1

Screen interval 1, 2 and 2.5

yrs

1 year 1 year 1 year 1 year Randomisation

1 or 2 yrs

NA

Screen arm 7515 2052 1864 1276 1613 1185 and 1182 2,000

Control arm 7907 2052 1857 1196 1593 1630 2,000

Age at randomisation (yrs ±

SD)

59 (6) 57 (5) 58 (5) 65 (5) 61 (4) 59 (6) NA

Current smokers at

randomisation

55% 76% 61% 55 % 65% 63% NA

Mean pack-years (± SD) 42 (19) 36 (13) 36 (18) 47 (25) 43 (18) 43 NA

Females 16% 45% 34% 0 % 35% 32% NA

Follow-up since

randomisation

6 yrs 5 yrs 3 yrs 6 yrs 6 yrs 5 yrs NA

PY of follow-up** 90,655 23,248 2,031 13,541 14,453 5,589 NA

European randomized CT screening trials:

Post-NLST J.K. Field , R. van Klaveren , J.H. Pedersen, U. Pastorino, E.Paci, N. Becker, M. Infante, Matthijs

Oudkerk H.J. de Koning

on behalf of the European Randomised Screening Trial Group.

* Last update August 2010; NA: not available or applicable; PY: Person-years; LC: lung

cancer; SD: standard deviation; yrs: years;**: cut off date 1-1-2011; ‡ Study recruiting.

• EU total ~17,000 screen arm

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What next and for whom?

IASLC J Thoracic Oncol 2012:Jan 7(1):10-19.

Strategic CT Screening Advisory Committee plans: identification of high-risk individuals for lung cancer CT screening

programs

develop radiological guidelines for use in developing national screening programs

develop guidelines for the clinical work-up of "indeterminate nodules" resulting from CT screening programmers

guidelines for pathology reporting of nodules from lung cancer CT screening programs;

recommendations for surgical and therapeutic interventions of suspicious nodules identified through lung cancer CT screening programs; and

integration of smoking cessation practices into future national lung cancer CT screening programs.

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U.S. Population Estimates from NHANES Courtesy of Peter Bach

Criteria Total

Population

Women Men Current

Smokers

Former

Smokers

55-74, ≥30 pack

years, ≤15 years

quit

7,425,000 3,220,000 4,205,000 4,027,000 3,398,000

50-79, ≥20 pack years, ≤10 years quit

13,500,000 5,816,000 7,684,000 9,114,,000 4,386,000

≥50, smoking history

46,481,000 20,147,000 26,334,000 14,729,000 31,752,000

≥21, ≥10 years

of smoking any

amount

77,005,000 33,805,000 43,200,000 39,883,000 37,122,000

Existing Guidelines

Organization Type of

Statement

NLST Like

Subjects?

Others?

ACCP/

ASCO/

ATS endorsed

Evidence based

guideline Suggest it be offered No

ACS Guideline May be considered No

ALA Guidance Recommended No

NCCN Consensus

guidelines Recommended

Yes, for some

individuals

AATS Guideline Recommended

Age 50-79; 20

pack years and five

year cumulative

risk of 5% or more;

lung cancer

survivors

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Estimates of Screening Avertable Deaths

Screen NLST population (55 – 74; current or former

smokers of 30 pack years, smoked within 15 years)

% of cancers: 26.7%

With 80% compliance 5% of lung cancer deaths averted

(8,150) Pinsky and Berg, JMS 2012:19(154-156)

Separate estimate by ACS researchers

Screen 8.6 million; Full compliance 12,250 deaths

averted; 70% compliance 8575 deaths averted Ma J et al Cancer on-line February 25, 2013

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Risk Prediction Models to Determine who to screen

Several models exist

Tammemagi et al JNCI 2011 includes

Age, Education, Family history of lung cancer

BMI, Self-reported COPD, CXR in last three years

Current smoker; pack years smoked, smoking duration

Former smokers: years since quit

Bach, Spitz, LLP, COSMOS

NCCN: Back of the envelope risk

Incremental Value Of Pulmonary

Function In Lung Cancer Risk Prediction

(Cancer Prev Res; 4(4); 1–11. 2011)

ROC AUCnested 0.72

ROC AUCfull 0.77

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Original Article Selection Criteria for Lung-Cancer Screening

Martin C. Tammemägi, Ph.D., Hormuzd A. Katki, Ph.D., William G. Hocking,

M.D., Timothy R. Church, Ph.D., Neil Caporaso, M.D., Paul A. Kvale, M.D., Anil K. Chaturvedi, Ph.D., Gerard A. Silvestri, M.D., Tom L. Riley, B.Sc., John

Commins, B.Sc., and Christine D. Berg, M.D.

N Engl J Med

Volume 368(8):728-736 February 21, 2013

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>2% Lung Risk Index

N=2537

Cancer N=76

>2% Lung Risk Index

and

>30 Pack Years

N=2306

Cancer N=66

PLCO Model Versus 30 Pack-Years

Pan-Canadian Lung Cancer Screening Study

• Compares to 30 pack-yrs

as threshold, using PLCO

Model, 9% <30 pack-yrs but

13% more lung cancers are

identified

• 3% lung cancers in < 2

years of follow-up

• 3.3% lung cancers age 55

to 74 yrs

CISNET Modeling to inform USPSTF

Full individual level NLST data to provide to four lung cancer screening modeling teams to validate and improve current models

Focus on extrapolating trial results to answer additional questions considered to be of value for medical practitioners, policymakers etc. including: Ages to initiate and end regular screening (encompasses total

number of screens)

Frequency of screens

Impact of longer follow-up and additional screens on mortality reduction

Smoking history that determines eligibility for screening

CISNET to then work with USPSTF

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NLST Data, Image and Specimen Access

Website https://biometry.nci.nih.gov/cdas/studies/nlst/

Access to entire research community

Data transfer agreement required

Name, email, summary of research proposal on website

Return of research papers requested for tracking and posting

Biospecimens http://www.acrin.org/RESEARCHERS/POLICIES/NLSTACRINBIOREPOSITORY.aspx

Summary

Opportunity to significantly improve outcome of patients with lung cancer

Selection of high-risk group to screen critical

Research to minimize burden of false-positives also critical

International collaboration to better define the screening process and most cost-effective diagnostic and treatment pathways

Screening is NOT a substitute for effective tobacco control policies

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Acknowledgements

Full list of all collaborators http://www.nejm.org/action/showSupplements?doi=10.1056%2

FNEJMoa1102873&viewType=Popup&viewClass=Suppl

Special thanks to Martin Tammemägi

NLST Executive Committee

Denise R. Aberle, MD

Christine D. Berg, MD

William C. Black, MD

Timothy R. Church, PhD, MS

Richard M. Fagerstrom, PhD

Barbara Galen, MSN, CRNP, CNMT

Ilana F. Gareen, PhD

Constantine Gatsonis, PhD

Jonathan Goldin, MD, PhD

Barnett S. Kramer, MD, MPH

David Lynch, MD

Irene Mahon, RN, MPH

Pamela M. Marcus, MS, PhD

Dorothy Sullivan

Carl J. Zylak, MD

National Cancer Institute:

DCP, EDRG, Lung Screening Study

DCTD, Cancer Imaging Program, Bethesda, MD

American College of Radiology Imaging Network, Philadelphia, PA

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NLST Lead Radiologists

ACRIN

Gerald Abbott MD, Denise Aberle MD, Judith Amorosa MD, Richard Barr MD, William Black MD,

Phillip Boiselle MD, Caroline Chiles MD, Robert Clark MD, Lynn Coppage MD, Robert Falk MD,

Elliot Fishman MD, Jonathan Goldin MD PhD, Eric Goodman MD, Eric Hart MD, Elizabeth

Johnson MD, Phillip Judy PhD, Ella Kazerooni MD, Robert Mattrey MD, Barbara McComb MD,

Geoffrey McLennan MD, Reginald Munden MD, James Ravenel MD, Michael Sullivan MD,

Stephen Swensen MD, Drew Torigian MD, Kay Vydareny MD, John Worrell MD

LSS

Peter Balkin MD, Matthew T. Freedman MD MBA, Kavita Garg MD, David S.Gierada MD,

Subbarao Inampudi MD, Howard Mann MB BCh, William Manor DO, Hrudaya Nath MBBS DMR

MD, David L. Spizarny MD, Diane C. Strollo MD, John Waltz MD

NLST Physicists

CT Physics Committee Dianna Cody, PhD MD Anderson Cancer Center

Mike McNitt-Gray, Phd UCLA

Christopher Cagnon, PhD UCLA

Philip Judy, PhD Brigham and Women’s Hospital

Fred Larke, PhD University of Colorado

Randell Kruger, PhD Marshfield Clinic

Mike Flynn, PhD Henry Ford Hospital

Xizeng Wu, PhD University of Alabama

CXR Physics

Committee

J. Anthony Seibert, PhD

UC Davis

Chris Cagnon, PhD UCLA

Philip Judy, PhD Brigham and Women’s Hospital

Randell Kruger, PhD Marshfield Clinic

Mike Flynn, PhD Henry Ford Hospital

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NLST Committees

Endpoint Verification Team

Anthony B. Miller, MB, Chair, Martin J. Edelman, MD, William K. Evans, MD, Robert S.

Fontana, MD, Mitchell Machtay, MD

Oversight Committee

Robert C. Young, MD, Chair, David Alberts, MD, David DeMets, PhD, Peter Greenwald,

MD, Dr PH, Paula Jacobs, MD, Theresa C. McLoud, MD, David P. Naidich, MD, James

Tatum, MD

Data and Safety Monitoring Board

Edward A. Sausville, MD, PhD, Chair, Wylie Burke, MD, PhD, Gene Colice, MD, Brenda

Edwards, PhD, Scott Emerson, MD, PhD, John Fletcher*,MD, Sylvan Green*,MD,

Russell Harris, MD, MPH, Jeffrey S. Klein, MD, Edward L. Korn, PhD, Robert Mayer,

MD, Joe V. Selby, MD, MPH, David W. Sturges, JD, Bruce W. Turnbull, PhD, Thomas J.

Watson, MD

* Deceased

Additional Partners

National Cancer Institute: Cancer Imaging Program, DCTD

Early Detection Research Group, DCP

ACRIN | Westat | IMS | CARE Communications

Our many, many site investigators and research staff

Colleagues NLST ACRIN Tissue Bank & Biomarker Oversight Committee

NLST ACRIN Research Evaluation Panel

ACRIN Specimen Biorepository at University of Colorado

UCLA Tissue Microarray Laboratory

American Cancer Society: in-kind assistance with recruitment

Advocates & members of lung cancer community who supported NLST

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With appreciation

53,454 trial participants

without whom these studies would not have been possible

I told you

smoking is bad

for you