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%)