National Lung Screening Trial Results Ella A. Kazerooni, M.D. Professor & Director Cardiothoracic Radiology Associate Chair for Clinical Affairs University of Michigan
NLST STOPPED! Lung cancer trial results show mortality benefit with low-dose CT 11/4/10 NCI Press Conference & Press Release The trials independent Data Safety Monitoring Board notified the NCI Director that the accumulated data provided statistically convincing answer to the study s primary question. This is the first time that we have seen clear evidence of a significant reduction in lung cancer mortality with a screening test in a randomized controlled trial. Christine Berg if low-dose helical CT screening is implemented responsibly and individuals with abnormalities are judiciously followed, we have the potential to save thousands of lives. Denise Aberle
NLST: Interim Primary Endpoint Analysis Reported by DSMB Oct. 20, 2010 Arm Person years (py) Lung cancer deaths Lung cancer mortality per 100,000 py Reduction in lung cancer mortality (%) Value of test statistic Efficacy boundary CT 144,097.6 354 245.7 20.3 3.21 2.02 CXR 143,363.5 442 308.3 Deficit of lung cancer deaths in CT arm exceeds that expected by chance, even allowing for multiple looks at the data
NLST: Interim Secondary Endpoint Analysis Reported by DSMB Oct. 20, 2010 Arm Person years (py) Deaths All-cause mortality per 100,000 py Reduction in all-cause mortality (%) Value of test statistic Value for significance CT 167,389.9 1870 1117.2 6.9 2.27 1.96 CXR 166,328.2 1996 1200.0 Deficit of deaths in CT arm exceeds that expected by chance.
NLST: Subjects Age & Gender
NLST: Subjects Race/Ethnicity
NLST: Subjects Smoking History
NLST: Family History of Lung Cancer CT CXR Total Any first degree relative 21.8 % 21.7 % 21.7 % Two or more first degree relatives 3.3 % 3.2 % 3.3 %
NLST Demographics vs. US Population U.S Census Department Tobacco Use Supplement of Continuing Population Survey for 2002-2004 Information on 240,000 respondents Reviewed subset of respondents aged 55-74, with 30+ pack year smoking, either current smoker or former smoker who quit within the past 15 years Identified smoking status, age, sex, race, ethnicity, marital status, and education
NLST Demographics vs. US Population NLST US Census Male (%) 59.0 58.5 Age 55-59 (%) 42.8 35.2 60-64 (%) 30.6 29.3 65-69 (%) 17.8 20.8 70-74 (%) 8.8 14.7 Race/ethnicity Black (%) 4.4 5.5 Hispanic (%) 1.7 2.4
NLST Demographics vs. US Population NLST US Census Married 66.6 60.0 Education < HS 6.1 21.3 College 31.5 14.4 Current smoker 48.2 57.1 Median pack years 48.0 47.0
NLST Demographics vs. US Population Compared with similar US population, NLST subjects have: similar gender distribution and smoking exposure are younger better educated less likely to be current smokers
Screening Exam Compliance & Crossover Study Year CT CXR Total Expected Screened Expected Screened Expected Screened T0 26,713 98.5% 26,722 97.5% 53,435 98.0% T1 26,282 94.0% 26,398 91.3% 52,680 92.6% T2 25,935 92.9% 26,097 89.5% 52,032 91.2% Compliance: 95% CT arm & 93% CXR arm Crossover: 4.3% in LSS CXR arm underwent CT
NLST: Screen Positivity* Rate CT CXR Screening Round # screened # positive % positive # screened # positive % positive 1 26,309 7,191 27.3 26,035 2,387 9.2 2 24,715 6,901 27.9 24,089 1,482 6.2 3 24,102 4,054 16.8** 23,346 1,174 5.0** All 3 75,126 18,146 24.1 73,499 5,043 6.9 *A positive screen is one that may be suspicious for lung cancer. **A suspicious abnormality that has been stable for 3 rounds may be called negative according to protocol.
NLST: True and False Positive Screens CT CXR Round 1 N (%) Round 2 N (%) Round 3 N (%) Round 1 N (%) Round 2 N (%) Round 3 N (%) Total positives 7,193 (100) 6,902 (100) 4,054 (100) 2,387 (100) 1,482 (100) 1,175 (100) With lung cancer 270 (4) 168 (2) 211 (5) 136 (6) 65 (4) 78 (7) Without lung cancer 6,923 (96) 6,734 (98) 3,843 (95) 2,251 (94) 1,417 (96) 1,097 (93)
indeterminate lung nodule
NLST (+) CT screen & diagnostic tests 1.4% experienced a complication 28% among those determined to have lung cancer 0.35% determined to not have lung cancer 16 deaths due to medical interventions hastened the death of 16 people of the 16, 10 had lung cancer and 6 did not risk of death in non-cancer patients 0.024%
NLST: Clinically Significant Non Lung Cancer CT CXR Screening Round # screened # positive % positive # screened # positive % positive 1 26,309 2695 10.2 26,035 785 3.0 2 24,715 1519 6.1 24,089 429 1.8 3 24,102 1408 5.8 23,346 361 1.5 All 3 75,126 5622 7.5 73,499 1575 2.1
NLST: Cumulative # of Lung Cancers
NLST: Cumulative # of Lung Cancer Deaths
Kaplan-Meier Curves for Lung Cancer Mortality
Kaplan-Meier Curves for All-Cause Mortality
Kaplan-Meier Curves for Lung Cancer Case Survival (Lung Cancer Cause of Death) Table 11.5.3d
National Lung Screening Trial Results Ella A. Kazerooni, M.D. Professor & Director Cardiothoracic Radiology Associate Chair for Clinical Affairs University of Michigan