Post on 22-Aug-2020
Dr. Laureano Molins
Cirurgia Toràcica
Hospital Clínic, Hospital Sagrat Cor, Barcelona
19 de gener de 2011
SCCT
CRIBATGE DEL CÀNCER DE PULMÓ: RESULTATS
BIBLIOTECA
BIBLIOTECA
CA Cancer J Clin 2009; 59:225-249
5 year Survival
Lung 14%
Colon 64%
Breast 89%
Prostate 99%
BIBLIOTECA
1963 1989 – 95 2009
Colon 43 62* 65
Breast 63 85* 85
Prostate 50 92* 93
Lung 8 14 16
(* = p<0.05)
5 YEAR CANCER SURVIVAL (MAYO CLINIC)
BIBLIOTECA
Non Small Cell Lung Cancer Surgery
• 1st cause of mortality from cancer
• Tobaco related in 90-95%
• Complete surgical resection is best chance
for cure
• 25% are “early stage” and potentially curable
BIBLIOTECA
0
10
20
30
40
50
60
70
80
90
100
Stage 1a
Stage 1b
Stage 2a
Stage 2b
Stage 3a
Stage 3b
Stage 4
5 Year
Survival Rate
Non Small Cell Lung Cancer
Cure Rate by Stage BIBLIOTECA
0
10
20
30
40
50
60
70
Percent
Stage
IA IB IIA IIB IIIA IIIB IV
LUNG CANCER SURVIVAL
Mountain CF. Chest 1997; 111: 1710-7
BIBLIOTECA
0
200
400
600
800
1000
1200
1400
1600
IA IB IIA IIB IIIA IIIB IV
Stage
Mountain CF. Chest 1997; 111: 1710-7
LUNG CANCER PRESENTATION
BIBLIOTECA
GCCB-S4,24 cm.
¡We want to change!
BIBLIOTECA
Prevention
Treatment
Early detection
LUNG CA BIBLIOTECA
Rationale for Screening Seems Intuitive
Overall 5-year survival 12%
Stage I 5-year survival 60-70%
% Stage I 14%
BIBLIOTECA
• HYPOTHESIS
• Find more cancers
• Find them earlier
• Increase chance of resectability
• Increase cure rate
Lung CancerScreening
BIBLIOTECA
• Non-Randomized Uncontrolled
(1950)
• Philadelphia Pulmonary Neoplasm
Research Project
• Veterans Administration Trial
• Tokyo Metropolitan Government Study
• South London Lung Cancer Study
• 20,000 pts. – No Benefit from
Screening CXR
Prior Screening Trials BIBLIOTECA
• Non-Randomized Controlled (1959-
1972)
• North London Cancer Trial
• Erfurt County Study
• Both showed
↑ % early cancers
↑ Resectability
↑ Survival rates
• No reduction in lung cancer mortality
Prior Screening Trials BIBLIOTECA
• Randomized Controlled (1970’s)
• Johns Hopkins Lung Project
• Memorial Sloan-Kettering Lung Project
• Mayo Lung Project
• Czechoslovakian Study
• 37,000 people enrolled
• Extensive analysis
Prior Screening Trials BIBLIOTECA
Johns Hopkins Annual CXR vs. Annual CXR
Memorial-Sloan +
Kettering Sputum Cytology
(q 4 mos)
Mayo Lung Project CXR + Sputum vs. Recommendation
Cytology (q 4 mos) of annual
assessment
Screening: The NCI Trials BIBLIOTECA
Years After Diagnosis
Survival
(%)
Mayo Lung ProjectIncidence Lung Cancer Survival
BIBLIOTECA
• Randomized Controlled (1970’s)
Better resectability in screened lung ca.
Better 5y survival in screened patients
No reduction in global mortality
CxR and sputum cytology not recommended as screening
Prior Screening Trials BIBLIOTECA
U.S. Preventive Services Task Force Grades and Recommendations
for Lung cancer Screening (1996)
Grade D Recommendation
The USPSTF recommends against routinely
providing (the service) to asymptomatic persons.
The USPSTF found at least fair evidence that (the
service) is ineffective or that harms outweigh the
benefits.
U.S. Preventive Services Task Force*, Ann intern Med 2004; 140:738-739.
BIBLIOTECA
DUPLICATION TIME BIBLIOTECA
SIZE / PROGNOSIS
PATZ, EF. et al. Chest 2000; 117: 1568-71
68%T2
82%T1
81%2,3 – 3,0
87%1,6 – 2,3
85%0,9 – 1,6Duke Univ.
80%0,2– 0,9510PATZ, EF et al.
Superv. 5 a.CmPacAUTOR
BIBLIOTECA
Author Pat. Cm 5y surv-
NARUKE T. (Jpn) 975 0 - 1 85%
1 - 2 85%
2 - 3 77%
NARUKE T. et al. Ann Thorac Surg 2001; 71: 1759-64
SIZE / PROGNOSIS BIBLIOTECA
GCCB-S. Eur Resp J 1999; 14: 812-6
63%T1 - T2 No1205
41%> 7
58%4,1 – 7
67%2,1 – 4GCCB-S
78%0,1 – 22361López Encuent A
2y surv.CmPatAUTHOR
SIZE / PROGNOSIS BIBLIOTECA
Deaths / N MST 5-Year
pT1, <=2cm 492/ 1816 NR 77%
pT1, >2-3 cm 582/ 1653 113 71%
pT2, <=5 cm 1311/ 2822 81 58%
pT2, >5-7 cm 461/ 825 56 49%
pT2, > 7 cm 240/ 364 29 35%
pT3 338/ 619 36 41%
0%
20%
40%
60%
80%
100%
0 5 10 15Years After Surgery
Survival by tumor size in patients with
pT1-T3 pN0 R0 TNM 7th Edition BIBLIOTECA
CT Screening Trials
• Japanese Trials
• I-ELCAP
• NELSON
(Dutch/Belgian)
• Mayo Clinic Lung
Screening Project
What About High-Tech Machines?
BIBLIOTECA
• Kaneko M et al, Radiology 1996; 201:798-802
• Sone et al, Lancet 1998; 351:1242-45
KANEKO
(1996)
SONE (1998)
Patients 1369 5483
Lung Ca. diagnosed 15 (0,3%) 19(0,48%)
No view at CxR 11 15
SCREENING - CT BIBLIOTECA
3 radiologists, 2 pneumologists, 1 thoracic surgeon, 1 oncologist, 1 epidemiologist
• 1,000 smokers > 65 years of age.
• Baseline and annual LDCT
• Work up algorithm – growth of NCN
ELCAPEarly Lung Cancer Action Program
Henschke et al., Lancet, 1999;354:99
BIBLIOTECA
1.000 persons: >60 y. y >10 paq/year (46% f)
Non calcified detected nodules: 363
(23% of patients)
Nodules confirmed as LC: 27 (7,4%)
SCREENING – Cornell Univ. ELCAP
1 nodul 159
2-3 nodules 59
4-6 nodules 46
Biger nodule <5 mm 58%
Henschke CI et al, Lancet 1999; 354: 99-105
BIBLIOTECA
CA. PULMÓN: ACTITUD ANTE LOS HALLAZGOS DEL CRIBAJE
1.000 Initial; 363 nodules in 233 patients (23%)28 Biopsies 27 Malignant (12%)
1 Benign
1.184 Repeated: 30 new nodules (2,5%) 16 persist after 1 month (1,4%)8 Biopsies 7 Malignant (44%)
1 Benign
2/36 Benign biopsies 5,5% + 3 non recomended biopsies Benign
Henschke CI et al. NY Acad Science 2001; 952: 124-34
ELCAP / BIOPSIES FOLLOWING PROTOCOL
BIBLIOTECA
Abril 2009 Mayo 2010 Nov 2010
Henschke CI et al. NY Acad Science 2001; 952: 124-34
SCREENING ELCAP / MALIGNANT NODULES
27 BASELINE: 15 mm
18 Adenocarcinoma4 Adenosquam3 Bronchoalveolar1 Squamous1 Atipical Carcinoid
22 IA1 IB1 IIB3 IIIA
7 REPEAT: 7 mm
6 Adenocarcinoma
1 Small Cell Ca
6 IA 86%
1 IIIA
85%
BIBLIOTECA
1.520 persons >50y and 20 paq/year (48% female)
Non calcified detected noduls: 1.358 in 782 patients
(51% of patients)
Noduls confirmed as LC: 17 (1,2%) (13 mm)
SCREENING – MAYO CLINIC
< 4 mm 39 %
4-7 mm. 50 %
8-20 mm. 10 %
>21 mm. 1 %
Swensen S et al.Am J Respir Crit Care Med 2002; 165: 508-13
BIBLIOTECA
Indeterminate
Nodule on Initial CT
< 3 mm
Thin section CT (1-3 mm
collimation) at 6 months
Benign Indeterminate
Follow-up CT in 6 months, if stable, follow with annual scan
Mayo CT Screening Trial
Nodule Management Algorithm BIBLIOTECA
Indeterminate
Nodule on Initial CT
4 -7 mm
Thin section CT (1-3 mm
collimation) at 3 months
Benign Indeterminate
Follow-up CT at 3 months, if stable, again in 3 months
Mayo CT Screening Trial
Nodule Management Algorithm BIBLIOTECA
Indeterminate Nodule
on Initial CT
8-20 mm
Thin section CT Now
Benign Indeterminate
Nodule enhancement
study (CT, PET)
>21 mm
Biopsy or
removal
>15HU <15 HU: CT
in 3 months
Mayo CT Screening Trial
Nodule Management Algorithm BIBLIOTECA
Low-dose CT Screening Studies
NCC-
Japan
Mayo Munster ELCAP Shinshu
Smoking
hx (pk yr)
20 20 20 10 NS
Age 50 50 40 60 40
Subjects 1369 1520 919 1000 5483
L.C. (%) 15 (0.43) 15 (1) 13 (1.4) 27 (2.7) 19 (0.35)
Stage I 93% 80% 62% 85% 87%
BIBLIOTECA
Grade B recommendation
The USPSTF concludes that the evidence is
insufficient to recommend for or against screening
asymptomatic persons for lung cancer with either
low dose CT or CXR, sputum cytology or a
combination of these tests.
U.S. Preventive Services Task Force*, Ann intern Med 2004; 140:738-739.
U.S. Preventive Services Task Force
Recommendations for Lung Cancer
Screening(2004) BIBLIOTECA
• International consortium – 40+ centers
• USA, Europe, Asia
• Annual screening with LDCT
• Started in 2000 - 50.000 participants
I-ELCAP BIBLIOTECA
• 28,689 participants
• 464 diagnosis of cancer
• 436 NSCLC
• Relationship between size and stage
Arch Int Med 2006; 166: 321-325
I-ELCAP Results I BIBLIOTECA
15mm 16-25 mm 26-35 mm 36 mm
Total 258 118 40 20
% N0M0 91% * 83% * 68% * 55%
NSCLC - 436
Arch Int Med 2006; 166: 321-325
I-ELCAP Results I BIBLIOTECA
• Screening is a process, not a single test
• Baseline: 13% have a positive result
• Annual: 5% have a positive result
Low-dose
CT
Positive
result
Work-up
algorithm
Diagnosis of
lung cancer
I-ELCAP
Regimen of screening BIBLIOTECA
• 31.567 baseline screenings
• 4.186 positive (13%)
• 405 cancer (1,3%)
• 5 interval cancer
• 27.456 annual
screenings
• 1.460 positive (5%)
• 74 cancer (0,3%)
• 0 interval cancer
N Engl J Med 2006;355:1763-71
484 cancer
412 Stage I (85%)
I-ELCAP Results II BIBLIOTECA
• Biopsies: 92% positive for lung cancer
• Surgical mortality: 0,5%
• Pathology panel (revision of 375 cancers)
• 356 (95%) showed signs of invasion (pleural,
basal membrane, vascular, bronchial)
N Engl J Med 2006;355:1763-71
I-ELCAP Results II BIBLIOTECA
BIBLIOTECA
10-year Kaplan-Meier survival
All cases 484 431 354 279 181 90 50 28 16 9 2
Resected Stage I 300 279 241 191 119 59 34 18 12 7 1
Resected clinical Stage I: 92% (95% CI: 88%-95%)
All cases: 80% (95% CI: 74%-85%)
No. at risk
BIBLIOTECA
1. Real influence of detection of smaller tumors
2. “Overdiagnosis” (tumors that do not affect the patient´s life)
3. “Healthy patients”
4. Cost-efective?; Cost of a life saved?
BIBLIOTECA
PROBLEMS WITH SCREENING
Stage I Lung Cancers: With and Without Treatment
Number 5-yr
Survivors
Rate
•Unresected 114 9 8%
•MSKCC 5 0 0%
•JH 29 1 3%
•Mayo: 11 1 9%
•Japan 69 7 10%
BIBLIOTECA
Years After Diagnosis
Survival
(%)
Mayo Lung ProjectIncidence Lung Cancer Survival
BIBLIOTECA
Resection of potentially curable lung ca.
Minimize resection of benign nodules.
LUNG CA SCREENINGOBJECTIVES
BIBLIOTECA
Broncoscopy
F. N. A.
Videothoracoscopy
Thoracotomy
NODULE BIOPSY BIBLIOTECA
< 2 (cm) 2 - 4(cm) > 4 (cm)
Fletcher 2% 40% 63%
Wallace 11% 43%
Cortese 11% 64%
Hanson 11% 62%
BRONCOSCOPY BIBLIOTECA
F.N.A. BIBLIOTECA
Small nodules: CT guided biopsy
8 mm POSITIVE NSCLC
European randomized trials comparing
CT to no screening.
• Netherlands-Belgium (NELSON)(4 centers): 15.822 2003-2009.
• Denmark (DLCST)(Copenhagen): 4.104. 2004-2010
• Germany (LUSI)(Heidelberg): 4.000. 2007-2014
• Italy (ITALUNG)(4 centers); 3.000. 2004-2010
BIBLIOTECA
Management of Lung Nodules Detected
by Volume CT Scanning
CONCLUSIONS: Among subjects at high risk for lung cancer who
were screened, the chances of finding lung cancer 1 and 2 years
after a negative first-round test were 1 in 1000 and 3 in 1000,
respectively.
First round: 2.6% of the participants had a positive test result.
Second round: 1.8% of the participants had positive test result
Round one: Sensitivity: 94.6% (95% confidence interval [CI], 86.5 to 98.0)
Negative predictive value 99.9% (95% CI, 99.9 to 100.0).
In the 7.361 subjects with a negative screening result in round one, 20 lung
cancers were detected after 2 years of follow-up.
NELSON STUDY: 7.557 participants underwent CT screening in
years 1, 2, and 4 of a randomized trial of lung-cancer screening.
N Engl J Med 2009;361:2221-9.
BIBLIOTECA
National Lung Screening Trial
(NLST)
• Accrual complete
• Follow-up 4-5 years
• Result expected in 2010
• 90% power for 20% reduction in LCSM
53,000 current/former (10y)
smoker (>30p/y) 55-74 yrs old
( / )
Annual CT x3 CxR x3
BIBLIOTECA
NLST (4 nov, 2010)
• Se detiene prematuramente el estudio tras análisis
preliminar:
• Mortalidad en grupo TC había disminuido ya un 20.3%
con respecto al grupo control: 354 vs 442.
• Mortalidad por cualquier causa había disminuido un
7% (25% por LC; otras: Enf. Cardiovascular)
• Todos los participantes notificados con indicación de
hablar con MF:
• A los del grupo control para considerar TC de cribado.
• A los del grupo TC para considerar continuar con TC.
• Pendiente de publicación
BIBLIOTECA
NY-ELCAP
• Tasa de mortalidad CV con el grado de
calcificación.
• CAC 0: 1.2%
• CAC 1-3: 1,8%
• CAC 4-6: 5,0%
• CAC 7-12: 5,3%
• CAC >4:*OR 2.1 (IC 95% 1.4-3.1,
p=0.0002) Radiology 2010 257:541-548
PROGRAMA DE DESHABITUACIÓ TABÀQUICA I
PROJECTE DE CRIBATGE PER AL DIAGNOSTIC PRECOÇ
DEL CÀNCER DE PULMÓ (CP)
Proposta BIBLIOTECA
10-year Kaplan-Meier survival
All cases 484 431 354 279 181 90 50 28 16 9 2
Resected Stage I 300 279 241 191 119 59 34 18 12 7 1
Resected clinical Stage I: 92% (95% CI: 88%-95%)
All cases: 80% (95% CI: 74%-85%)
No. at risk
BIBLIOTECA
MOLTES GRÀCIES PER
L’ATENCIÓ!
* Ajustado a sexo, edad, paquetes-años
Radiology 2010 257:548
BIBLIOTECA