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Incidental Findings on Low-Dose CT Lung Cancer Screening in the NLST and Risk of Respiratory Disease Mortality


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In an analysis of data from the National Lung Screening Trial (NLST) reported in Chest, Pinsky et al found that incidental respiratory disease–related findings on low-dose computed tomography (CT) screening were common and associated with an increased risk of mortality from respiratory diseases.

Study Details

The study involved data from 25,002 subjects (of a total of 26,722) in the NLST low-dose CT group who received a baseline and subsequent low-dose CT screening; 23,574 received all three screenings in the trial. Incidental findings were categorized and assessed for association with respiratory disease mortality.

Covariates in multivariate analysis of respiratory disease mortality included demographic characteristics (age, sex, race), body mass index (BMI), smoking history (current smoking status, pack-years), and reported history of respiratory disease (chronic obstructive pulmonary disease [COPD], emphysema, chronic bronchitis, asthma, pneumonia). 

Incidental Findings

Prior to screening, emphysema, chronic bronchitis, or COPD was reported by 17.3% of participants, with emphysema or COPD reported by 10.6%. Emphysema on low-dose CT was reported in 30.7% of subjects at the baseline screen and in 44.2% at any screen. Emphysema on low-dose CT was more common in subjects with vs without a reported history of emphysema or COPD (52.4% vs 28.1% at baseline); 18% of those with emphysema on baseline low-dose CT had a reported history of emphysema or COPD.

The second most common incidental finding was reticular opacities (including honeycombing, fibrosis, scar), identified in 20.1% of subjects at the baseline screening and in 36.8% on any screening. Pleural thickening or effusion was identified in 5.6% at the baseline screening and in 10.6% of any screening. Less common findings included adenopathy, atelectasis, and consolidation (≤ 3% at any screening).

Mortality Risks

Median follow-up for mortality was 10.3 years (interquartile range = 9.7–10.7 years). There were a total of 3,639 non–lung cancer deaths, including 708 from respiratory disease. Among subjects with a history of emphysema or COPD, 10-year respiratory disease mortality rates ranged from 3.7% among those with neither finding on low-dose CT to 17.3% among those with both on low-dose CT. Among subjects without a history of emphysema or COPD, 10-year respiratory disease mortality rates ranged from 1.1% among those with neither abnormality on low-dose CT to 3.9% among those with both.

On multivariate analysis, emphysema identified on low-dose CT was significantly associated with an increased risk of respiratory disease mortality (hazard ratio [HR] = 2.27, 95% confidence interval [CI] = 1.92–2.7), as were reticular opacities identified on low-dose CT (HR = 1.39, 95% CI = 1.19–1.62) and a history of emphysema or COPD (HR = 3.41, 95% CI = 2.89–4.02). 

Additional factors significantly associated with an increased risk of respiratory disease mortality were older age (HR = 2.0 for 65–69 years and 4.03 for ≥ 70 years at last screening vs 55–64 years), male sex (HR = 1.28), current smoking (HR = 1.78),  ≥ 50 vs < 50 pack-year history (HR = 1.56), history of pneumonia (HR = 1.30), and history of asthma (HR = 1.58). Factors not significantly associated with an increased risk were pleural thickening or effusion on low-dose CT, Black race, history of chronic bronchitis, and BMI ≥ 30 kg/m2.

On a multivariate analysis of respiratory disease mortality risk according to baseline (prevalent) vs subsequent (incident) findings on low-dose CT screening, hazard ratios for prevalent and incident findings were: 2.52 (95% CI = 2.11–3.01) and 1.74 (95% CI = 1.37–2.20) for emphysema; 1.15 (95% CI = 0.88–1.51) and 0.97 (95% CI = 0.71–1.31) for pleural thickening or effusion; and 1.30 (95% CI = 1.09–1.56) and 1.45 (95% CI = 1.20–1.75) for reticular opacities.

As noted by the investigators: “It is unknown what diagnostic or therapeutic interventions, if any, were performed as follow-up to the findings of non–lung cancer–related pulmonary abnormalities observed on CT scanning. However, because these were incidental findings in a lung cancer screening trial, follow-up was probably not generally intensive. For subjects with emphysema at baseline, only around 20% had an associated overall screen result of [radiologist rating of negative for lung cancer with clinically significant non–lung cancer–related abnormalities], suggesting this finding was often regarded as not clinically significant.”

The investigators concluded: “Incidental respiratory disease–related findings observed on NLST [low-dose] CT screens were frequent and associated with increased mortality from respiratory diseases.”

Paul F. Pinsky, PhD, of the Division of Cancer Prevention, National Cancer Institute, is the corresponding author of the Chest article.

Disclosure: The investigators reported that there was no specific funding for the current study. For full disclosures of the study authors, visit chestnet.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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