Benjamin Besse, Philippe Girard 1ers MACA – Ajaccio – 10 mai 2012
Jan 13, 2016
Benjamin Besse,Philippe Girard
1ers MACA – Ajaccio – 10 mai 2012
LUNG CANCERIncidence = 1,600,000/yrMortality = 1,370,000/yr
Lethality ≈ 85%
Cancer Incidence and Mortality (world)
Screening: why ?
• Goal: cancer mortality reduction
• Detect asymptomatic cancers
• Asymptomatic cancers = better prognosis
(?)
31%Stade III
31%Stade III
38%Stade
IV
38%Stade
IV
24%Stade
I
24%Stade
I
7%Stade II
7%Stade II
Clinical Stages and Survival/Prognosis
Fry, Cancer 1999;86:1867-76Groome, IASLC Lung Cancer staging project, JTO 2007;2:694-705
Screening for Lung CancerWhat Tools ?
• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine…)
Lung Cancer Screening Tools
• Sputum Cytology
• Chest X-ray
Bach, ACCP guidelines, Chest 2007;132:69S-77S
The PLCO (Prostate, Lung, Colorectal and Ovarian) trial
Oken, JAMA 2011;306(17):1865-1873
• 3 annual chest X-rays (n=77445) vs usual care (n=77456)• 55-74 yrs, 45% never smokers
Number of lung cancers
1696 vs 1620
Oken, JAMA. 2011;306(17):1865-1873
Deaths from lung cancer
1213 vs 1230
The PLCO (Prostate, Lung, Colorectal and Ovarian) trial
• 3 annual chest X-rays (n=77445) vs usual care (n=77456)• 55-74 yrs, 45% never smokers
Screening for Lung CancerWhat Tools ?
• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine…)
Bach, ACCP guidelines, Chest 2007;132:69S-77S
Lung Cancer Screening with CT
Diameter 2 mm 8 mm 40 mm 200mm
Nb of cells 4.106 3.108 33.109 4.1012
Screening « window »
Smith-Bindman, N Engl J Med 2010;10.1056
Computed Tomography (CT) of the Chest
938mGy/cm
15.9 mSv88mGy/cm
1.5 mSv
Routine Low-dose
ELCAP, NEJM 2006;355:1763-71
It works ?
• 31,567 subjects(1993-2005)
• 481 lung cancers detected
• 85% stage I (n=412)
Screening with Low-dose CT
National Lung CancerScreening Trial (NLST)
FumeursAnciens fumeurs≥ 30 PAAge 55-74
FumeursAnciens fumeurs≥ 30 PAAge 55-74
40,000PLCO
40,000PLCO
10,000ACRIN10,000ACRIN
Scanner low doseScanner low dose
RadiographieRadiographie
YearsYears00 11 22
RANDOMISATION
NLST, NEJM 2011; 365(5):395-409
n
« Positive »(diam>=4mm)
Lung cancers
Lung cancer deaths
Riskreduction
Low-dose CT
26.45518.146(68.5%)
1.060346
(1.3%)20,0%
Chest X-ray 26.2325.043
(19.2%)941
425(1.6%)
NLST: Trial discontinuation in oct. 2010 !
NNS to prevent 1 lung cancer death = 320…
NLST, NEJM 2011; 365(5):395-409
55 to 74 yrs, > 30P-Y, active or stop<15 yrs
• Probably healthier vs. base population
• < 65 years – 73% vs 65% in the base population
• Less current smokers– 48% vs 57%
• Better educated– 6% with less than a high school education vs
21%
NLST: Highly selected population
NLST, JNCI 2010
155 ponctions, 206 fibros, 297 chirurgies270 cancers ! (4%)
• NLST : Compliance > 90%
• Women adherence to mammography screening higher if – Younger– Higher education – Lived in an area with a higher percentage of
mammography facilities
NLST: Magic Compliance
Philips KA, Health Serv Res. 1998 Apr;33(1):29-53.
Cause of Death (CT group)n %
Reduction vs control group
Lung cancer 427 22.9%20%
(6.8 – 26.7, p <0.004)
Other Neoplasm 416 22.3%
3.2%(p = 0.28)
Cardiovasc. Illness 486 26.1%
Respiratory illness 175 9.4%
Complication of medical or surgical care
12 0.6%
Other 349 18.7%
All 18656.2%
(1.2 – 13.6%, p = 0.02
NLST, NEJM 2011; 365(5):395-409
• Deaths from lung cancer
NLST, NEJM 2011; 365(5):395-409
but…« NCI is not yet recommending such screening »
NLST: Trial discontinuation in oct. 2010 !
Unanswered Questions
• How to diminish the false positive rate ?
The NELSON trial(Nederlands-Leuvens Longkanker Screenings Onderzoek)
van Klaveren, NEJM 2009, 361:123
Automated volumetric measurment for non-calcified nodules
NPV of diagnostic strategy at 1 yr = 99.9%
4,147mm3
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
European Screening Trials Overview
NELSON DLCST ITALUNG LUSI DANTE MILD
Nr rounds 4 5 4 5 5 10 or 5
Enrollement 15,464 4,104 3,206 3,551 2,472 3,581
Completed Y Y Y N Y N
Baseline detection
0.9% 0.8% 1.5% 1.0% 2.2% 0.8%
Incidence 0.5% 0.6% 0.4% - 0.5% 0.5%
de Koning, ECCO-ESMO meeting, Sept. 2011
de Koning, ECCO-ESMO meeting, Sept. 2011
PISA position Statement (March 2011)
• 6 ongoing European trials have enrolled 32,000 subjects with about 150,000 person-years of follow-up (approx. half of NLST)
• European trials continuation !
• Concrete plan for interim analyses and/or pooling
• Discouragement of opportunistic screening outside clinical trials !
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?
How many screen rounds?
• Lung cancer was diagnosed frequently after the third low-dose CT screening
• This observation suggests that continuing to screen high-risk individuals annually will provide a net benefit.
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?
• False reassurance (license to smoke)?...
IELCAPI, NEJM 2006;355:1763-71
It works ?
• 31,567 subjects(1993-2005)
• 481 lung cancers detected
• 85% stage I (n=412)
Screening with Low-dose CT
Negative CT ?Keep smoking !
Positive CT ?Keep smoking !
(we can cure your cancer)
Screening routine nightmare
McMullan and Cohen NEJM 2006, 354 (4): 397
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?
• False reassurance (license to smoke)?...
• Where to go ?
Blood is the issue
• NSLT collected >100 000 blood samples
• Quit at age 50: risk reduction about 66%
Effects of Smoking Cessation on the Risk of Lung Cancer
Peto, BMJ 2000,321:323
Deal ?
1 CT scan (138 €) =
27 packs of cigarettes=
1 month of tobacco consumption=
2.5 months of nicotine substitutes
Séminaire de réflexion sur la littérature récente concernant le dépistage scanographique du
Cancer broncho-pulmonaire.
17-18 février 2012 – GOLF et IFCT
• Dépistage à l’échelon individuel
• Après information sur les bénéfices et risques encourus
• Sujets âgés de 55 à 74ans et ont fumés plus de 30PA
• Information sur sevrage tabagique impératif