Will CT screening reduce overall lung cancer mortality? Heidi - - PowerPoint PPT Presentation

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Will CT screening reduce overall lung cancer mortality? Heidi - - PowerPoint PPT Presentation

Apr 30, 2023 446 likes •866 views

Will CT screening reduce overall lung cancer mortality? Heidi Roberts MD FRCP(C) Heidi Roberts, MD, FRCP(C) Associate Professor of Radiology Department of Medical Imaging UHN / MSH / WCH Screening - Requirements Screening Requirements

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Will CT screening reduce overall lung cancer mortality?

Heidi Roberts MD FRCP(C) Heidi Roberts, MD, FRCP(C)

Associate Professor of Radiology Department of Medical Imaging UHN / MSH / WCH

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Screening - Requirements Screening Requirements

  • important health problem

important health problem

  • detectable risk factor or disease marker
  • simple, safe, precise and validated test
  • the screening program is effective

g p g

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Screening - Requirements Screening Requirements

  • lung cancer - important health problem

lung cancer important health problem

– frequent and lethal – Canada 2008

23 900 new diagnoses

  • 23,900 new diagnoses
  • 20,200 deaths

5 year survival rate 15% – 5-year survival rate 15%

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Screening - Requirements Screening Requirements

  • important health problem

important health problem

  • detectable risk factor or disease marker

smoking cessation programs in effect – smoking cessation programs in effect – large smoking population

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Screening - Requirements Screening Requirements

  • detectable risk factor or disease marker

detectable risk factor or disease marker

– large ex-smoking population

10 year mortality for lung cancer by 10 year mortality for lung cancer by smoking status

Smoker-life long Nonsmokers Smokers-quit aged 50 yo Smokers-quit aged 60 yo smokers-quit aged 70 yo 25 30 35 en 10 15 20 deaths/100 me 5 25 30 35 40 45 50 55 60 65 70 75 80 85 Age (years)

courtesy N Young, NZ

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Screening - Requirements Screening Requirements

  • important health problem

important health problem

  • detectable risk factor or disease marker

i l f i d lid t d t t

  • simple, safe, precise and validated test
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Screening - Requirements Screening Requirements

  • simple safe precise and validated test

simple, safe, precise and validated test

– Low-Dose Computed Tomography

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Low-Dose CT Low Dose CT

  • helical CT

helical CT

  • multi-slice
  • 120 kV

120 kV, 40-80 mA, 1.25 mm

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LDCT for lung cancer screening LDCT for lung cancer screening

  • 1st landmark publication:

1 landmark publication: C Henschke et al. ELCAP Lancet 1999

“Spotting Lung

“CAT SCAN PROCESS

Lung Cancer B f It'

“CAT SCAN PROCESS COULD CUT DEATHS FROM LUNG CANCER”

Before It's Too Late”

FROM LUNG CANCER”

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ELCAP: Screening Results ELCAP: Screening Results

3

% f d % Stage I cancers found

2 2.5

2.7% 2.3%

% cancers found cancers found

1 1.5 0.5

0.7% 0.4%

1 2

CT CXR

LDCT detects Stage I lung cancers

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PMH screening results PMH screening results

  • first 1,000

first 1,000

  • 2.2% malignancies
  • 2% lung cancer

2% lung cancer

  • 78% Stage 1

Roberts et al. CARJ 2007

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Screening - Requirements Screening Requirements

  • important health problem

important health problem

  • detectable risk factor or disease marker
  • simple, safe, precise and validated test
  • the screening program is effective

g p g

heated discussion …..

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Screening effectiveness Screening effectiveness

  • measured as survival
  • measured as survival

I-ELCAP

  • 27,456
  • non-randomized
  • 10-year-survival
  • up to 92%*

up to 92%

Henschke et al, New Eng J Med 2006

SCREENING IS EFFECTIVE NOT SCREENING CAUSES HARM

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Screening effectiveness Screening effectiveness

  • measured as mortality

measured as mortality

  • can only be addressed in randomized trials

NLST

  • randomized

randomized

  • 53,000
  • LDCT vs. chest X-ray
  • aims to report in 2012

p

  • primary outcome: mortality
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Screening effectiveness Screening effectiveness

  • measured as mortality

measured as mortality

  • can only be addressed in randomized trials

NELSON trial ITALUNG Netherlands, Belgium, Denmark 20,000 LDCT vs. general care 3,000 LDCT vs. general care

MORTALITY BENEFIT NOT PROVEN EFFECTIVENESS OF SCREENING UNPROVEN SCREENING CAUSES HARM

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Survival vs Mortality Survival vs. Mortality

  • 10-year survival up to 92%

10 year survival up to 92% l i l ≠ d d t lit

  • longer survival ≠ reduced mortality
  • survival biased by

– lead time bias lead time bias – length time bias – overdiagnosis

  • verdiagnosis
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Lead time bias

Sy - Dx death no no survival no screen no screen CT - Dx screen i l survival lead time

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Overdiagnosis bias

death no Dx autopsy no no no screen no screen CT - Dx screen

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Length time bias

screen death Sy - Dx screen slow-growing cancer Sy - Dx death aggressive cancer screening detects slow-growing cancers aggressive cancers elude screening tests

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Does CT screening reduce mortality? Does CT screening reduce mortality?

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Does CT screening reduce mortality? Does CT screening reduce mortality?

evidence unproven benefit survival

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Does CT screening reduce mortality? Does CT screening reduce mortality?

lead time bias length time bias di i evidence unproven benefit survival

  • verdiagnosis

risk of morbidity (harms) from invasive dx procedures surgery g y for benign lesions radiation risk

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Reducing Mortality Reducing Mortality

Length time bias

  • prevent the treatment of slow-growing cancers
  • individual biological potential?

– size

– growth rate growth rate – angiogenic and metastatic potential – mitotic rate – mutation rate – immunological host response

  • simplest biological profile to date is growth rate
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Growth rate Growth rate

  • growth rate

growth rate

– common rule: 2 years stable = benign doubling time < 30 days & > 500 days benign – doubling time < 30 days & > 500 days benign

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3 months doubling time 72 days combined small cell-large cell neuroendocrine carcinoma

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Overdiagnosis?

3 months no growth no growth biopsy: malignant cells surgical resection 1.1 cm bronchioloalveolar carcinoma no invasion

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July 2007 March 2008 July 2008 growth rate ~380 days

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3 months same size, higher density , g y adenocarcinoma

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3 months measurement? adenocarcinoma

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Reducing Mortality Reducing Mortality

Overdiagnosis

  • non-lethal, indolent cancer
  • aggressive cancer that is

gg

  • vertaken by lethal

competing morbidities

10 year mortality for lung cancer by smoking status

Smoker-life long Nonsmokers Smokers-quit aged 50 yo Smokers-quit aged 60 yo 25 30 35 en smokers-quit aged 70 yo 5 10 15 20 deaths/100 me 25 30 35 40 45 50 55 60 65 70 75 80 85 Age (years)

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Reducing Mortality Reducing Mortality

Overdiagnosis

  • non-lethal, indolent cancer
  • aggressive cancer that is

gg

  • vertaken by lethal

competing morbidities

decrease risk decrease prevalence

  • f lung cancer

decreased efficiency decrease risk

  • f comorbidites
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Does CT screening reduce mortality? Does CT screening reduce mortality?

lead time bias length time bias di i evidence unproven benefit survival

  • verdiagnosis

risk of morbidity (harms) from invasive dx procedures surgery g y for benign lesions radiation risk

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Reducing Mortality Reducing Mortality

Harms from diagnostic interventions for benign lesions (f l iti ) (false positives)

  • positive baseline: 15% 26%

I-ELCAP Toronto first 1,000

p

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Reducing Mortality Reducing Mortality

Harms from interventions for benign lesions

  • diagnostic interventions
  • CT-guided biopsies
  • ≤ 10 mm
  • 45 5% adequate for diagnosis

45.5% adequate for diagnosis

  • sensitivity for malignancy 67.7%
  • accuracy 78.8%
  • pneumothorax 52.7%, chest tube 9.1%

Ng, Patsios et al, 2008

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Reducing Mortality Reducing Mortality

Radiation risk

  • low-dose
  • how long screen?
  • how often screen?

annual (no change) baseline biennial

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Does CT screening reduce mortality? Does CT screening reduce mortality?

lead time bias length time bias

  • verdiagnosis

risk of morbidity (harms) from

evidence unproven benefit survival

risk of morbidity (harms) from invasive dx procedures surgery for benign lesions radiation risk

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SLIDE 37

Does CT screening reduce mortality? Does CT screening reduce mortality?

evidence unproven benefit survival

lead time bias length time bias

  • verdiagnosis

risk of morbidity (harms) from

survival

risk of morbidity (harms) from invasive dx procedures surgery for benign lesions radiation risk

false negatives biomarker genetic markers

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Reducing Mortality Reducing Mortality

False negatives

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Reducing Mortality Reducing Mortality

False negatives

  • combining LDCT with autofluorescence bronchoscopy
  • Pan-Canadian Screening study
  • 7 centers in Canada – including PMH
  • 2500 participants

2500 participants

  • funded by the Terry Fox Research Institute /

Canadian Partnership Against Cancer launched Sep 2008

  • launched Sep 2008
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Reducing Mortality Reducing Mortality

Individual profile

  • combining LDCT with
  • sputum analysis
  • blood analysis (biomarkers)

i k t risk assessment tumor management

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Does Screening Reduce Mortality? Does Screening Reduce Mortality?

  • mortality benefit directly addressed in randomized trials
  • mortality benefit directly addressed in randomized trials
  • dynamic process
  • factors influencing morbidity can be minimized

factors influencing morbidity can be minimized

  • depending on the setting

YES YES