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4/22/2013
1
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
22
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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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28
With appreciation
53,454 trial participants
without whom these studies would not have been possible
I told you
smoking is bad
for you
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