Lung Cancer screening :
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1 Lung Cancer screening : Pro-Contra SAMO interdisciplinary workshop on chest tumors 27 and 28 january 2017 Prof L.P.Nicod Sevice de pneumologie CHUV-Lausanne -CH
2 Lung Cancer How big is the problem? Epidemiology Leading cause of cancer death (28%) More than breast + prostate + colon + pancreas cancer Estimated increase in cancer rates by 2030: % Survival 5-year survival: lung cancer 15% compare: breast 89%, prostate 99%, colon 65% Only 16 % is diagnosed at an early stage US Congress. Lung Cancer Mortality Reduction Act of 2011
3 Lung Cancer Screening CT lung cancer screening aims to reduce lung cancer mortality with limited harms through early detection and treatment Benefits Lung cancer mortality reduction Reduction advanced disease Life years gained Harms False-positives Over diagnosis Over treatment High cardio-pulmonary co-morbidity Radiation risk Quality of life/ smoking behaviour Costs
4 I-ELCAP Lung Cancer Screening Trials Early Lung Cancer Action Project 405 cancers / baseline scans 74 cancers / follow-up scans 5 interval cancers 412 / 484 (85%) stage I Mainly adenocarcinomas I-ELCAP investigators. N Engl J Med 2006;355:1763 (1.3%) (0.27%)
5 Lung Cancer Screening Trials Early Lung Cancer Action Project 31,567 participants 410 cancers I-ELCAP investigators. N Engl J Med 2006;355:1763
6 National Lung Screening Trial The Largest Randomized Controlled Trial US: 53,000 participants (200 M$) in NLST
7 National Lung Screening Trial LDCT = 1060 lung cancers * CXR = 941 cancers * LDCT arm CXR Arm More cancers + more early stage cancers with LDCT Stage IA Stage IB-IIB Stage III-IV NLST research team. N Engl J Med 2011;365:395
8 National Lung Screening Trial Cancers found with CT/CXR Lung cancers More lung cancers were found with LDCT than CXR NLST research team. N Engl J Med 2011;365:395
9 Risks of Screening False-positives One or more lung nodules will be found in about half of the individuals screened for lung cancer although only few nodules actually represents lung cancer after (invasive) work-up. (unnecessary) work-up Complications with negative effect HRQoL, increased health care costs
10 National Lung Screening Trial Results NLST Mortality N f/u all-cause cancer others LDCT CXR months Participants: LDCT / CXR 20% reduction of lung-cancer specific mortality But Total number of lives saved was small (123/26722 = 0.4%)
11 Lung Cancer Screening Trials Randomized Controlled trials In Europe LDCT versus usual care Total NELSON NL/B , 1, 2, 4, 6y DLST DK , 1, 2, 3, 4, 5y 4104 LUSI GER , 1, 2, 3, 4, 5y >4000 MILD IT NA 0, 1, 2, 3, 4y 4099 ITALUNG IT NA 0, 1, 2, 3, 4y 3206 DANTE IT NA 0, 1, 2, 3, 4, 5y 2472 UKLS UK y >4000 LDCT versus CXR NLST USA , 1, 2, 3y 53454
12 Lung Cancer Screening Screening detects favorable cancer stages Newer trials NELSON, LUSI: More early stage cancers than in NLST Horweg N et al. AJRCCM 2013; 187(8):848
13 A Systematic Review to Update the USPSTF Recommendation Humphrey et al., Annals of Internal Medicine 2013
14 Lung Cancer Screening The European results All published European trials show so far no positive effect (in fact, most show a negative effect of LDCT) But Small numbers: participants, cancers NLST: participants, cancers Short follow-up: months NLST: 78 months Low pack-years: 20 pack-years NLST: 30 pack-years
15 Targeted screening: High risk selection Liverpool Lung Project (LLP v2 ) Population based invitation Cost effective CT screening Maximise specificity over sensitivity Identify more cancers per person screened Factors to target Smoking Exposure (duration or packyear) Targeted selection Age >50 yrs (90% of LC aged over 50 yr) Family Hx (2-3x risk) Respiratory diseases: COPD, Emphysemia; Bronchitis; pneumonia; TB. Previous malignant disease High risk Asbestos exposure
16 Results of the Danish Lung Cancer Screening Trial Risk factor subgroup analysis Mathilde M. W. Wille et al. AJRCCM: 193 ;542: 2016
17 Liverpool Lung Project (LLP) LLP-Risk Model - examples A man aged 64, 42 years smoking, history of other malignancy, relative with lung cancer aged over 60 at diagnosis, 5-year risk=9.5%- qualifies Woman aged 68, 26 years smoking, no other risk factors, 5-year risk = 1.5% - does not qualify Man aged 66, never-smoker, relative with lung cancer aged <60 at diagnosis, history of other malignancy and asbestos exposure and pneumonia. 5-year risk = 5.37% - qualifies
18 Management of screen-detected nodules Future management of screen detected pulmonary nodules will probably be based on volumetric assessment. Used by NELSON, DLCST, LUIS, MILD and UKLS A volume growth of 20% defined as growth by NELSON criteria is hardly appreciable by diameter measurement (8% diameter increase is no growth according to NLST criteria).
19 Nodule Management What is a positive result? NLST Any non-calcified nodule 4 mm NELSON Any solid component of a nodule 500 mm 3 Any solid component of a pleural based nodule 10 mm Any growing nodule with a volume doubling time < 400 d Any non-solid nodule growing > 20% in diameter NLST Research Team.NEJM 2011;365(3):395 van Klaveren R. NEJM 2009;361(23):2221
20 Subsolid nodules 1 Radiological evaluation Solid Nodule Classification of pulmonary nodules % at CT screening 18.9% Malignancy rate 7% Sub solid Nodule(SSN) Part solid Nodule Pure ground-glass nodule Pure (GGN) 1.6% 2.8% 63% 18% Etiology, probability of malignancy, pronosis and management is totally different Message N 1 : => Specific guidelines Henschke er al. CT screening for lung cancer:. AJR Am J Roentgenol 2002;178(5): , For ELCAP trial
21 Lung cancer Probability using the NELSON Trial data - Lancet Oct Calc. probability of developing lung cancer within 2 years for asymptomatic past & present smokers after a LDCT scan: -Stratified by risk of nodule Volume, & Volume diameter, & VDT. Used cancer probabilities to design nodule management protocols: Volume Doubling Time (days) In half of the participants no nodules were detected their 2 year probability of developing lung cancer is 0.4% - supporting a 2 year screening interval Volumes
22 Risks of Screening Radiation risk Attending annual screening (NLST) Up to 25 CT scans Estimated 8 msv per 3 years 1 radiation-induced cancer per 2,500 screened individuals in the next years Reduction in radiation dose CT Bach et al. JAMA 2012
23 Lung Cancer Screening Trails Summary Reduction in lung cancer-specific mortality: NLST No reduction in lung cancer-specific mortality: DANTE, ITALUNG, MILD, DLCST (Italy, Denmark) Results pending: NELSON, UKLS, LUSI (Netherlands/Belgium, Germany, UK) Potential explanation Lower risk: 20 vs. 30 pack-years, > 50 vs. > 55years Shorter follow-up / smaller numbers Larger number of interval cancers Differences in workup / treatment?
24 Implementation of sreening -CT lung cancer screening ideally for high-risk groups only But how to scale up risk-stratification based prevention programmes? -Requirement of evidence-based organised and protocolised approach Risk selection and recruitment technologies Training in imaging acquisition, image quality, and radiological image interpretation of the CT scans Nodule (volumetric) management Multidisciplinary work-up of screen-detected lung cancer Multidisciplinary oncology treatment of (early-stage screendetected) lung cancers Quality assessment
25
26 Cost-Benefits of Screening Cost-effectiveness CT lung cancer screening Systematic review estimates US$ 18,452 US$ 66,480 per life-year gained US$ 27,756 US$ 243,077 per QALY gained NLST estimates (chest X-ray vs CT) US$ 52,000 US$ 81,000 per QALY gained Modelling study Canada CAD$ 52,000 per QALY gained UKLS 8,466 per QALY gained (based on baseline screening) Threshold??? (WHO: 3x GDP ) Raymakers et al, Appl Health Econ Health Policy 2016; Puggina et al. Eur J Public Health 2016; Black et al. N Engl J Med 2014; Goffin et al. JAMA Oncol 2015
27 The sreening of lung cancer is attractive, but remain several uncertainties! Thanks for your attention Saas-Fee
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