Benjamin Besse, Philippe Girard

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


• 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 !




• 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.





• 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





• 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

Documents

Benjamin Besse, Philippe Girard