The study evaluated annual low-dose helical CT screening versus standard chest x-ray for lung cancer screening in high-risk individuals aged 55-74 years who were heavy smokers. Over 53,000 participants were randomized across 33 sites in the U.S. The trial was stopped early based on a recommendation when interim results found a 20% reduction in lung cancer mortality with CT screening. CT screening found more positive cases but also had higher false positive rates compared to chest x-ray.
2. ¨ High risk population
¡ Heavy smoker or former smoker (quit within last 15 years)
ú Smoked 30 pack years equivalent to 1 pack /day x 30 years
¡ Age: 55 to 74 years
¨ Randomized to:
¡ low-dose helical CT OR
¡ standard chest X-ray
¨ Duration: yearly x 3 years and follow up for 5 years
¨ Positive cases are further verified
¨ Endpoint: death from lung cancer
4. ¨ Started 2002
¨ Accrued 53 000 in 33 sites in USA over 20 months
¨ DSMB stopped the trial in October 2010
5. Spiral CT Chest xray P
Numbers 26500 26500
No of cases ? ?
Lung cancer mortality 354 442 <0.05
RR of lung cancer death 0.8 (20% lower) 1
All-cause mortality 7% lower
Positive findings on imaging during study 24% 7%
False positives 95-98% 93-96%
Compliance 91%
6.
7.
8. ¨ Primary Prevention:
¡ Prevent initial disease occurrence
¨ Secondary Prevention:
¡ Detect the disease early in the asymptomatic
stage
¨ Tertiary Prevention:
¡ Prevent re-occurrence and complications and
disability and improve QOL
9.
10. ¨ High risk groups:
¡ Heavy cigarette smokers
¨ Asymptomatic
11. ¨ Primary Prevention:
ú Anti-smoking measures bilat mastectomy
ú HBV vaccination
ú HPV vaccination
¨ Secondary Prevention:
ú Breast cancer screening
ú HCC screening
¨ Tertiary Prevention:
ú Proper treatments
ú Adj Tam in breast cancer
12. Lung cancer
¨ Clinical exam: X
¡ BSE, CBE
¡ DRE
¨ Lab tests: X
¡ Serum biomarkers:
ú PSA
ú AFP
¡ Cytology
¨ Radiology: YES
¡ Mammography - Chest X-ray XXXX
¡ TRUS - CT chest
¡ ABD US - MRI?
¨ Other: XXX
¡ Colonoscpoy - Bronchoscopy
13.
14. A. Conventional
B. Spiral (low dose helical):
¡ scans the entire chest in about 7-15 seconds during a
single, breath-hold. The CT scanner rotates around the
person, who is lying still on a table as the table passes
through the center of the scanner.
15.
16.
17.
18.
19.
20. ¨ Lead time bias
¨ Length bias
¨ Overdiagnosis bias
21. ¨ Survival is the time from Diagnosis to death
¨ It is longer if cancer is detected early by screening
¨ Lead time= screening survival – symptom survival
¨ To avoid it
measure mortality
22. ¨ Indolent cancers have long preclinical phase and
more amenable to early detection
23. ¨ Diagnosis and treatment of non-fatal disease
24. ¨ High risk population
¡ Heavy smoker or former smoker (quit within last 15 years)
¡ Age: 55 to 74 years
¨ Randomized to:
¡ low-dose helical CT OR
¡ standard chest X-ray
¨ Duration: yearly x 3 years and follow up for 5 years
¨ Positive cases are further verified
¨ Endpoint: death from lung cancer
26. ¨ Started 2002
¨ Accrued 53 000 in 33 sites in USA over 20 months
¨ DSMB stopped the trial in October 2010
27. Spiral CT Chest xray P
Numbers 26500 26500
Lung cancer mortality 354 442 <0.05
Mortality /100 000 245 308
RR 0.8 (20% lower) 1
All-cause mortality 7% lower
Positive findings on imaging during study 24% 7%
False positives 95-98% 93-96%
Compliance 91%
28. ¨ Who is at high risk?
¨ Age?
¨ Schedule?
¨ Compliance?
¨ False positive rates?
¨ Stop or not to stop smoking?
29. Lung cancer No lung cancer
(cases) (non-cases)
Spiral CT mass True positive (TP) False positive (FP) PPV:
5% 95% TP/test positive
Spiral CT no mass False negative (FN) True negative (TN) NPV:
TN/test negative
Test Sensitivity: Test Specificity:
TP/cases TN/non-cases
30. ¨ Positivity rate or prevalence of positivity = Total positives / Total tested x 100
49.70%
¨
¨ Negativity rate or prevalenve of negativity = Total negatives / Total tested x 100
50.30%
¨
¨ Rate of Disagreement = (False positives + False negatives) / Total tested x 100
8.73%
¨
¨ Rate of Agreement = (True positives + True negatives) / Total tested x 100
91.27%
¨
¨ Sensitivity = True positives / Total positives x 100
84.85%
¨
¨ Specificity = True negatives / Total negatives x 100
97.60%
¨
¨ Predictive value positivity = True positives / Tested positive x 100
97.22%
¨
¨ Predictive value negativity = True negatives / Tested negative x 100
86.70%
31. ¨ Females:
¡ Breast
¡ Cervix
¨ Males:
¡ Prostate
¨ Both sexes:
¡ Colorectal
¡ Lung
¡ ? HCC in Egypt in high risk groups