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Early Lung Cancer Screening: An Update of the Current Evidence. Simon Martel, MD IUCPQ Quebec , Canada. No conflict of interest. Lung Cancer Epidemiology. Most frequent cause of cancer death In 2020 = 5 th cause of death

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Early Lung Cancer Screening: An Update of the Current Evidence

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Early lung cancer screening an update of the current evidence l.jpg

Early Lung Cancer Screening:An Update of the Current Evidence

Simon Martel, MD

IUCPQ

Quebec, Canada


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No conflict of interest


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Lung Cancer Epidemiology

  • Most frequent cause of cancer death

  • In 2020 = 5th cause of death

  • In 2010 (Canada) = 11200 deaths in men and 9400 deaths in women (27% of all cancer deaths)

  • Overall survival at 5 years around 15%

  • 90% of cases attributable to smoking and 50% of new cases in former smokers


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Fundamentals of Screening

  • The purpose of screening is to detect a disease at a stage when cure or control is possible

  • At risk population for a specific disease is submitted to a test to identify asymptomatic persons having the disease

  • Persons with a positive result will then be evaluated to determine whether they actually have the disease


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Fundamentals of Screening

  • Characteristics of a good screening test and program:

    • Reasonable sensitivity and specificity

    • Accessible with a low cost

    • Low associated morbidity

  • There should be an effective treatment at an early stage of the disease


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Screening Bias

Patz EF et al. New Eng J Med 2000


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Screening Bias

Patz EF et al. New Eng J Med 2000


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Screening Bias

Black WC. Cancer 2007


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Fundamentals of Screening

  • A good lung cancer screening program should reduce lung cancer mortality and overall mortality in the screened group compared to the unscreened group


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1950-1990

  • Randomised and non randomised controlled trials:

    • John Hopkins Lung Project

    • Memorial Sloan Kettering Lung Project

    • Mayo Lung Project

    • Czechoslovakian Study

    • North London Cancer Study

    • Erfurt County Study

    • Kaiser Permanente Study

  • Chest radiograph ± sputum cytology every 4 to 12 months compared to less frequent or no screening over 3 to 16 years

  • 52000 subjects in intervention groups and 48000 in control groups


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1950-1990

  • Intervention groups:

    • More lung cancers

    • More early stage lung cancers

    • More resectable lung cancers

  • No reduction in lung cancer mortality


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Recommendations

Bach BP et al. Chest 2007


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Are we done with chest X-ray

in lung cancer screening?

J Natl Cancer Inst 2005


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Radiation

« Persons at risk for repeated radiation exposure, such as workers in health care and the nuclear industry, are typically monitored and restricted to effective doses of 100 mSv every 5 years (i.e. 20 mSv per year), with a maximum of 50 mSv allowed in any given year. »

Fazel R et al. New Eng J Med 2009


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Radiation


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Radiation

  • Low dose CT

Baldwin DR et al. Thorax 2011


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CT lung cancer screening

Black WC. Cancer 2007


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CT lung cancer screening

Black WC. Cancer 2007


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CT lung cancer screening

Black WC. Cancer 2007


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CT lung cancer screening

  • What have we learned from these studies?

    • Management of small pulmonary nodules

    • CT can detect early stage lung cancer

    • Excellent survival in a majority of screened cases

    • More epidemiology

    • More and more adenocarcinomas…

    • Overdiagnosis? Slow growing tumors?


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Follow-up of nodules

MacMahon H et al. Radiology 2005


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Thorax 2011


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Early stage detection

New Eng J Med 2006


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Overdiagnosis?


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Growth Model of Lung Cancer

Bach BP et al. Chest 2007


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CT Randomised Controlled Trials

  • DEPISCAN (France)

  • ITALUNG trial (Italy)

    • 3 206 participants

    • Active and former smokers 55-69 years old

    • Chest CT annually for 4 years vs no screening

  • NELSON Trial (Dutch-Belgian)

    • 15 248 participants (2004-2006)

    • Chest CT at 0, 1 and 3 years vs no screening

    • Active and former smokers 50-75 years old


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CT Randomised Controlled Trials

  • DANTE Trial (Italy)

    • 2472 participants, male, 60-75 years old (2001-2006)

    • Chest X-ray and sputum cytology at baseline (all)

    • Chest CT at 0, 1, 2, 3 and 4 years vs annual medical visit

    • Active and former smokers of at least 20 pack-years


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DANTE trial

Infante M et al. Am J Respir Crit Care Med 2009


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CT Randomised Controlled Trials

  • NLST (USA)

    • 53 456 participants (2002-2004)

    • Chest CT vs radiograph at 0, 1 and 2 years

    • Active and former smokers 55 to 74 years-old

  • Results

    • 20.3% reduction in lung cancer mortality (354 deaths vs 442 deaths)

    • All-cause mortality lower by 7% in the CT group


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NLST Participants


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Pan-Canadian Early Detection of Lung Cancer Study

  • Validate a lowcostriskmodeling to select a population with a higherrisk of lung cancer

  • Evaluate the add-on impact of spirometry, bloodbiomarkers and AFB in a screening strategy

  • Evaluate the impact of the screening modalities on the quality of life

  • Evaluate the cost of implementing a lung cancer screening in Canada


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Pan-Canadian Early Detection of Lung Cancer Study

Enrolled N=2533

AFB = 1252

66 lung cancers confirmed


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478 Normal CT Scans at Baseline (20%)


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Pan-Canadian Early Detection of Lung Cancer Study

  • Nodules of course

  • Other findings:

    • Kydney cyst or mass

    • Adrenal nodule

    • Interstitial lung disease

    • Coronary calcifications

    • Thoracic aorta aneurism

    • Thyroid nodule


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Conclusions

  • We are not ready for lung cancer screening

  • Low dose CT might be an interesting tool but many questions to answer

    • Lung cancer mortality reduction?

    • Overall mortality reduction?

    • Magnitude of overdiagnosis?

    • Morbidity associated with screening?

    • Cost of this type of screening?

  • SMOKING CESSATION is still a priority!


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Screening Bias

Black WC. Cancer 2007


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1950-1990

Manser RL et al. Thorax 2003


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1950-1990

Manser RL et al. Thorax 2003


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1950-1990

Manser RL et al. Thorax 2003


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Radiation

Brenner DJ et al. New Eng J Med 2006


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Radiation

Brenner DJ et al. New Eng J Med 2006


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New Engl J Med 2009


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Coûts-Bénéfices?

Am J Respir Crit Care Med 2008


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Coûts-Bénéfices?

  • Étude PLuSS

    • 3 642 sujets avec TDM de base

    • 3 423 sujets avec TDM répété à 1 an

    • 1 477 sujets avec nodules au TDM initial

    • 821 sujets ont eu une ou des études supplémentaires (TDM et/ou TEP) avant le TDM à 1 an


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Coûts-Bénéfices?

Wilson DO et al. Am J Respir Crit Care Med 2008


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Coûts-Bénéfices?

Bach PB et al. Chest 2007


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Overdiagnosis?


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Follow-up of nodules


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Lung Cancer Risk Assessment Model

  • Age

  • Smoking history

  • History of COPD (self-reported)

  • Chest X-ray in last 3 years

  • Family history

  • Education

  • Body mass index

M Tammemagi & PLCO Study Group


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66 Confirmed Cancers

*Normal at baseline


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