Lung Cancer Screening with Computer Aided Detection Chest Radiography: Design and Results of a Randomized, Controlled Trial

<div><p>Introduction</p><p>The sensitivity of CT based lung cancer screening for the detection of early lung cancer is balanced by the high number of benign lung nodules identified, the unknown consequences of radiation from the test, and the potential costs of a CT based screening program. CAD chest radiography may improve the sensitivity of standard chest radiography while minimizing the risks of CT based screening.</p> <p>Methods</p><p>Study subjects were age 40–75 years with 10+ pack-years of smoking and/or an additional risk for developing lung cancer. Subjects were randomized to receive a PA view chest radiograph or placebo control (went through the process of being imaged but were not imaged). Images were reviewed first without then with the assistance of CAD. Actionable nodules were reported and additional evaluation was tracked. The primary outcome was the rate of developing symptomatic advanced stage lung cancer.</p> <p>Results</p><p>1,424 subjects were enrolled. 710 received a CAD chest radiograph, 29 of whom were found to have an actionable lung nodule on prevalence screening. Of the 15 subjects who had a chest CT performed for additional evaluation, a lung nodule was confirmed in 4, 2 of which represented lung cancer. Both of the cancers were seen by the radiologist unaided and were identified by the CAD chest radiograph. The cumulative incidence of symptomatic advanced lung cancer was 0.42 cases per 100 person-years in the control arm; there were no events in the screening arm.</p> <p>Conclusions</p><p>Further evaluation is necessary to determine if CAD chest radiography has a role as a lung cancer screening tool.</p> <p>ClinicalTrials.gov identifier NCT01663155</p> </div

Characteristics of actionable nodules identified on the baseline screen.

<p>Characteristics of actionable nodules identified on the baseline screen.</p

The assumptions made in calculating the required sample size for this study.

<p>With 4000 subjects per study arm, we expected to have 90% power at 5 years to detect a 50% reduction in symptomatic lung cancer <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059650#pone.0059650-Obuchowski1" target="_blank">[14]</a>.</p

Characteristics of study subjects.

<p>Characteristics of study subjects.</p

Flow of study subjects through the trial.

<p>Flow of study subjects through the trial.</p

Comparison of SVID and metastases by MRI and age:

<p>A) Radiologic evaluation of SVID and metastases was based on comparison of post-contrast and FLAIR images. Note that metastases were obviously demarcated after gadolinium (Gd) injections, while SVID visible in FLAIR were not. The <i>red circles</i> refer to the locations of SVID or metastases in FLAIR or post-Gd images. B) Age distribution of patients affected by SVID or metastases. Patients with no metastases were younger than those with metastatic brain tumor; patients with SVID were significantly older than those without small vessel disease.</p

Relationship between SVID severity and metastatic brain tumor:

<p>The data are presented as % (filled symbols) or as a ratio between SVID severity in the two subsets of patients.</p

SVID grading methods, brain metastases identification, and metastatic distribution:

<p>A) Grading for SVID: deep white matter hyperintense signals, periventricular hyperintensity, and combined. Each represents the SVID distribution of grades of those with and without brain metastases. Differences were significant for deep white matter hyperintensity (p = 0.04), periventricular hyperintensity (p = 0.01), and the combined (p = 0.02). B) MRI image with gadolinium contrast demonstrates the protocol used to count identifiable metastases. These are indicated by empty red circles. C) Distribution of metastases in different CNS regions. Note that in the region where SVID are most common (cerebrum) there was a statistically significant difference in the number of metastases as predicted by a protective effect of SVID against tumor growth. See text for details.</p

Characteristics of lung cancer patients compared between those who presented with and those who presented without brain metastases.

<p>SD = standard deviation, SVID = small vessel ischemic disease.</p

Colorimetric Sensor Array (CSA) system.

<p>(A) CSA. (B) CSA-embedded blood culture bottle. (C) CSA prototype blood culture instrument.</p