1. Benjamin Besse, Philippe Girard
1ers MACA – Ajaccio – 10 mai 2012
Benjamin Besse, Philippe Girard

2. Cancer Incidence and Mortality (world)
LUNG CANCER
Incidence = 1,600,000/yr
Mortality = 1,370,000/yr
 Lethality ≈ 85%

3. Screening: why ? Goal: cancer mortality reduction
Detect asymptomatic cancers
Asymptomatic cancers = better prognosis (?)

4. Clinical Stages and Survival/Prognosis
31%
Stade III
38%
Stade IV
24%
Stade I 7%
Stade II
31. Non-Small Cell Lung Cancer: Stages at Presentation
NSCLC patients typically present with advanced disease. Approximately one third of NSCLC patients present with early localized disease amenable to surgical treatment.
Fry, Cancer 1999;86:
Groome, IASLC Lung Cancer staging project, JTO 2007;2:

5. Screening for Lung Cancer What Tools ?
Sputum cytology
Chest X-ray
Chest CT
Autofluorescence bronchoscopy
Markers (serum, exhaled air, urine…)

6. Lung Cancer Screening Tools
Sputum Cytology
Chest X-ray
Bach, ACCP guidelines, Chest 2007;132:69S-77S

7. 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
Number of lung cancers
1696
vs 1620
Oken, JAMA 2011;306(17):

8. 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
Deaths from lung cancer
1213
vs 1230
Oken, JAMA. 2011;306(17):

9. Screening for Lung Cancer What Tools ?
Sputum cytology
Chest X-ray
Chest CT
Autofluorescence bronchoscopy
Markers (serum, exhaled air, urine…)

10. 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 2007;132:69S-77S

11. Computed Tomography (CT) of the Chest
Routine
Low-dose
938mGy/cm
15.9 mSv
88mGy/cm
1.5 mSv
Computed Tomography (CT) of the Chest -- Routine (Left) versus Low Dose (Right). The surveillance of small pulmonary nodules is a common indication for chest CT, and several protocols can be used for these studies. Routine chest CT (Panel A) is associated with a radiation dose to the patient that is 10 times that of low-dose chest CT (Panel B) (dose-length product, 938 mGy per centimeter vs. 88 mGy per centimeter; effective dose, 15.9 mSv vs. 1.5 mSv) -- yet each shows the small pulmonary nodule equally well (Panels A and B, arrows). The pulmonary parenchyma and upper abdomen are better visualized on the higher-dose routine scan (Panels A and C, respectively) than the low-dose scan (Panels B and D, respectively), but these areas are irrelevant to follow-up of a small pulmonary nodule. A recent survey of radiologists who perform chest CT showed that low-dose CT was not routinely used for examinations performed solely for the purpose of nodule follow-up and that most radiologists were unaware of the CT settings used for initial versus follow-up CT.1 Standardization of CT protocols could result in substantial reduction in patients' radiation doses without loss of diagnostic accuracy. Images courtesy of Dr. Michael J. Flynn, Department of Radiology, Henry Ford Health Systems.
Smith-Bindman, N Engl J Med 2010;

12. Screening with Low-dose CT
It works ?
31,567 subjects
( )
481 lung cancers
detected
85% stage I
(n=412)
ELCAP, NEJM 2006;355:

13. National Lung Cancer Screening Trial (NLST)
Fumeurs Anciens fumeurs
≥ 30 PA Age 55-74
40,000 PLCO
10,000 ACRIN
Scanner low dose
Radiographie
Years 1 2
RANDOM I S A T ON
NLST, NEJM 2011; 365(5):

14. NLST: Trial discontinuation in oct. 2010 !
55 to 74 yrs, > 30P-Y, active or stop<15 yrs n
« Positive »
(diam>=4mm)
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%)
NNS to prevent 1 lung cancer death = 320…
NLST, NEJM 2011; 365(5):

15. NLST: Highly selected population
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, JNCI 2010

16. 155 ponctions, 206 fibros, 297 chirurgies
270 cancers ! (4%)

17. NLST: Magic Compliance
NLST : Compliance > 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 Apr;33(1):29-53.

18. 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
1865
6.2% (1.2 – 13.6%, p = 0.02
NLST, NEJM 2011; 365(5):

19. Deaths from lung cancer
NLST: Trial discontinuation in oct !
Deaths from lung cancer
but…
« NCI is not yet recommending such screening »
NLST, NEJM 2011; 365(5):

20. Unanswered Questions
How to diminish the false positive rate ?

21. The NELSON trial (Nederlands-Leuvens Longkanker Screenings Onderzoek)
Automated volumetric measurment for non-calcified nodules
NPV of diagnostic strategy at 1 yr = 99.9%
4,147mm3
van Klaveren, NEJM 2009, 361:123

22. Unanswered Questions How to diminish false positive rate?
Should the ongoing trials go on?...

23. European Screening Trials Overview
NELSON
DLCST
ITALUNG
LUSI
DANTE
MILD
Nr rounds 4 5
10 or 5
Enrollement
15,464
4,104
3,206
3,551
2,472
3,581
Completed Y N
Baseline detection
0.9%
0.8%
1.5%
1.0%
2.2%
Incidence
0.5%
0.6%
0.4% -
de Koning, ECCO-ESMO meeting, Sept. 2011

24. 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

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

26. 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.

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

28. Screening with Low-dose CT
It works ?
31,567 subjects
( )
481 lung cancers
detected
85% stage I
(n=412)
Negative CT ?
Keep smoking !
Positive CT ?
Keep smoking !
(we can cure your cancer)
IELCAPI, NEJM 2006;355:

29. Screening routine nightmare
McMullan and Cohen NEJM 2006, 354 (4): 397

30. 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 ?

32. Blood is the issue
NSLT collected > blood samples

33. Effects of Smoking Cessation on the Risk of Lung Cancer
Quit at age 50:
risk reduction about 66%
Peto, BMJ 2000,321:323

34. 1 month of tobacco consumption 2.5 months of nicotine substitutes
Deal ?
1 CT scan (138 €) =
27 packs of cigarettes
1 month of tobacco consumption
2.5 months of nicotine substitutes

35. Dépistage à l’échelon individuel
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
GOLF :
Fabrice Barlési
Etienne Lemarié
GOLF :
Fabrice Barlési
Etienne Lemarié