Benjamin Besse, Philippe Girard

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Benjamin Besse,Philippe Girard
1ers MACA Ajaccio 10 mai 2012
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Cancer Incidence and Mortality (world)
LUNG CANCER Incidence 1,600,000/yr Mortality
1,370,000/yr ? Lethality 85
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Screening why ?

• Goal cancer mortality reduction
• Detect asymptomatic cancers
• Asymptomatic cancers better prognosis (?)

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Clinical Stages and Survival/Prognosis
Fry, Cancer 1999861867-76 Groome, IASLC Lung
Cancer staging project, JTO 20072694-705
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Screening for Lung CancerWhat Tools ?

• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine)

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Lung Cancer Screening Tools

• Sputum Cytology
• Chest X-ray

Bach, ACCP guidelines, Chest 200713269S-77S
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The PLCO (Prostate, Lung, Colorectal and Ovarian)
trial

• 3 annual chest X-rays (n77445) vs usual care
  (n77456)
• 55-74 yrs, 45 never smokers

Oken, JAMA 2011306(17)1865-1873
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The PLCO (Prostate, Lung, Colorectal and Ovarian)
trial

• 3 annual chest X-rays (n77445) vs usual care
  (n77456)
• 55-74 yrs, 45 never smokers

Deaths from lung cancer
1213 vs 1230
Oken, JAMA. 2011306(17)1865-1873
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Screening for Lung CancerWhat Tools ?

• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine)

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Lung Cancer Screening with CT
Screening  window 
Diameter 2 mm 8 mm 40 mm 200mm
Nb of cells 4.106 3.108 33.109 4.1012
Bach, ACCP guidelines, Chest 200713269S-77S
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Computed Tomography (CT) of the Chest
Routine
Low-dose
938mGy/cm 15.9 mSv
88mGy/cm 1.5 mSv
Smith-Bindman, N Engl J Med 201010.1056
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Screening with Low-dose CT

• It works ?
• 31,567 subjects
• (1993-2005)
• 481 lung cancers
• detected
• 85 stage I
• (n412)

ELCAP, NEJM 20063551763-71
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National Lung CancerScreening Trial (NLST)
RANDOM I S A T I ON
NLST, NEJM 2011 365(5)395-409
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NLST Trial discontinuation in oct. 2010 !
55 to 74 yrs, gt 30P-Y, active or stoplt15 yrs
n  Positive  (diamgt4mm) Lung cancers Lung cancer deaths Risk reduction
Low-dose CT 26.455 18.146 (68.5) 1.060 346 (1.3) 20,0
Chest X-ray 26.232 5.043 (19.2) 941 425 (1.6) 20,0
NNS to prevent 1 lung cancer death 320
NLST, NEJM 2011 365(5)395-409
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NLST Highly selected population

• Probably healthier vs. base population
• lt 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, JNCI 2010
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155 ponctions, 206 fibros, 297 chirurgies 270
cancers ! (4)
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NLST Magic Compliance

• NLST Compliance gt 90
• Women adherence to mammography screening higher
  if
• Younger
• Higher education
• Lived in an area with a higher percentage of
  mammography facilities

Philips KA, Health Serv Res. 1998 Apr33(1)29-53.
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Cause of Death (CT group)
n Reduction vs control group
Lung cancer 427 22.9 20 (6.8 26.7, p lt0.004)
Other Neoplasm 416 22.3 3.2 (p 0.28)
Cardiovasc. Illness 486 26.1 3.2 (p 0.28)
Respiratory illness 175 9.4 3.2 (p 0.28)
Complication of medical or surgical care 12 0.6 3.2 (p 0.28)
Other 349 18.7 3.2 (p 0.28)
All 1865 6.2 (1.2 13.6, p 0.02
NLST, NEJM 2011 365(5)395-409
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Deaths from lung cancer
NLST Trial discontinuation in oct. 2010 !
but  NCI is not yet recommending such
screening 
NLST, NEJM 2011 365(5)395-409
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Unanswered Questions

• How to diminish the false positive rate ?

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The NELSON trial(Nederlands-Leuvens Longkanker
Screenings Onderzoek)

• Automated volumetric measurment for
  non-calcified nodules
• NPV of diagnostic strategy at 1 yr 99.9

van Klaveren, NEJM 2009, 361123
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Unanswered Questions

• How to diminish false positive rate?
• Should the ongoing trials go on?...

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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
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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 !

de Koning, ECCO-ESMO meeting, Sept. 2011
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Unanswered Questions

• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?

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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.

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Unanswered Questions

• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?
• False reassurance (license to smoke)?...

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Screening with Low-dose CT

• It works ?
• 31,567 subjects
• (1993-2005)
• 481 lung cancers
• detected
• 85 stage I
• (n412)

Negative CT ? Keep smoking !
Positive CT ? Keep smoking ! (we can cure your
cancer)
IELCAPI, NEJM 20063551763-71
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Screening routine nightmare
McMullan and Cohen NEJM 2006, 354 (4) 397
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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 ?

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Blood is the issue

• NSLT collected gt100 000 blood samples

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Effects of Smoking Cessation on the Risk of Lung
Cancer

• Quit at age 50
• risk reduction about 66

Peto, BMJ 2000,321323
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Deal ?

• 1 CT scan (138 )
• 27 packs of cigarettes
• 1 month of tobacco consumption
• 2.5 months of nicotine substitutes

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Séminaire de réflexion sur la littérature récente
concernant le dépistage scanographique du Cancer
broncho-pulmonaire.

• 17-18 février 2012 GOLF et IFCT
• Dépistage à léchelon 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

• GOLF
• Fabrice Barlési
• Etienne Lemarié

• GOLF
• Fabrice Barlési
• Etienne Lemarié