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Lung Cancer Screening: Simulations of Effects of Imperfect Detection on Temporal Dynamics¹

¹ From the Department of Radiology, University of Pittsburgh, Imaging Research, Suite 4200, 300 Halket St, Pittsburgh, PA 15213 (B.E.C., D.G.); and Department of Radiology, Weill Medical College of Cornell University, the New York Hospital-Cornell Medical Center, New York, NY (D.F.Y., C.I.H.). Received January 9, 2004; revision requested March 10; revision received March 29; accepted April 28. Address correspondence to B.E.C. (e-mail: chapmanbe@upmc.edu).

View larger version (16K): [in a new window]   Figure 1a. Graphs show (a) the percentage of subjects with asymptomatic cancers and (b) the mean size of asymptomatic cancers. By year 20, both the population tumor burden and mean cancer diameter have leveled off to steady-state values, indicating that the population is in an appropriate state to begin the screening simulation.

View larger version (17K): [in a new window]   Figure 1b. Graphs show (a) the percentage of subjects with asymptomatic cancers and (b) the mean size of asymptomatic cancers. By year 20, both the population tumor burden and mean cancer diameter have leveled off to steady-state values, indicating that the population is in an appropriate state to begin the screening simulation.

View larger version (25K): [in a new window]   Figure 2. Graph shows distribution of VDT values for cancers in the screening population at baseline screening and for cancers that develop after baseline screening. VDT values (mean, 125 days ± 30) are generated from a Gaussian distribution. During the start-up period, tumors with shorter VDT values were more likely to become symptomatic, producing a positive shift in VDT values for tumors present at the onset of screening. Tumors that developed during the screening period were not affected. Because we used a Gaussian distribution, about two of every 100 000 cancers had a nonphysical negative VDT value. Such cancers were assumed to initiate but never grow.

View larger version (30K): [in a new window]   Figure 3a. Graphs show the percentage of screening subjects with (a) cancer detected with radiologic screening for three constant detection functions and (b) observed cancers. Zero indicates baseline screening. The action size for these functions was 2 mm. The percentage of observed cancers in the steady state is the same for all three functions. As the detection rate decreased, the percentage of subjects with cancers detected at baseline decreased. Missed tumors resulted in a transition period between baseline screening and steady-state screening; a larger percentage of cancers were detected with poorer performing techniques during transition screenings.

View larger version (32K): [in a new window]   Figure 3b. Graphs show the percentage of screening subjects with (a) cancer detected with radiologic screening for three constant detection functions and (b) observed cancers. Zero indicates baseline screening. The action size for these functions was 2 mm. The percentage of observed cancers in the steady state is the same for all three functions. As the detection rate decreased, the percentage of subjects with cancers detected at baseline decreased. Missed tumors resulted in a transition period between baseline screening and steady-state screening; a larger percentage of cancers were detected with poorer performing techniques during transition screenings.

View larger version (26K): [in a new window]   Figure 4. Graph shows mean diameters of detected cancers for the constant detection functions. Zero indicates baseline screening. Action size for detection was 2 mm. As detection rate decreased, mean diameter of detected cancers increased because of additional growth cycles prior to detection.

View larger version (24K): [in a new window]   Figure 5a. Graph shows the percentage of screening subjects with (a) cancers detected with CT and chest radiography (CXR) and (b) observed cancers. While chest radiography detected cancers in a smaller percentage of the population each year, during the steady state, the same percentage of patients had observed cancers in both CT and chest radiography screening.

View larger version (23K): [in a new window]   Figure 5b. Graph shows the percentage of screening subjects with (a) cancers detected with CT and chest radiography (CXR) and (b) observed cancers. While chest radiography detected cancers in a smaller percentage of the population each year, during the steady state, the same percentage of patients had observed cancers in both CT and chest radiography screening.

View larger version (21K): [in a new window]   Figure 6. Graph shows total number of screening subjects per year undergoing CT and chest radiography (CXR). Zero indicates baseline screening. As cancers are detected, patients are removed from the screening population. Because of the high sensitivity of CT, the screening population size decreases more rapidly after the baseline examination. In subsequent years, the screening population decreases at a similar rate for both CT and chest radiography. Because the available population is continually decreasing, steady-state behavior is demonstrated by looking at percentages.

View larger version (18K): [in a new window]   Figure 7. Graph shows mean diameters of cancers detected with CT and chest radiography (CXR) during each screening. Zero indicates baseline screening. For both CT and chest radiography, mean diameter of cancers detected with screening decreases to a steady-state value.

View larger version (24K): [in a new window]   Figure 8. Graph shows difference between the cumulative number of cancers detected with CT and chest radiography (CXR). Screening populations consisted of 10 000 asymptomatic subjects at baseline. Zero indicates baseline screening. The difference in the number of cancers observed at screening with CT and chest radiography is relatively constant over time and differs primarily by the number of cancers observed at baseline screening. The difference between the number of cancers detected with CT and the number of cancers detected with chest radiography, however, steadily increases over the course of the screening program.