Delays in Recommended Follow-Up after Positive Findings in Lung Cancer Screening.

Rationale: Lung cancer screening (LCS) is an effective tool to reduce mortality. However, barriers along the LCS care continuum, including delay in follow-up care, may reduce effectiveness. Objectives: The primary goals of this study were to evaluate delays in follow-up in patients with positive findings on LCS and to examine the impact of delay on lung cancer staging. Methods: This was a retrospective cohort study of patients enrolled in a multisite LCS program with positive LCS findings, defined as Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) 3, 4A, 4B, or 4X. Time to first follow-up was evaluated with delay considered >30 days beyond the standardized Lung-RADS recommendation. Multivariable Cox models were used to evaluate the likelihood of delay by Lung-RADS category. Participants with resultant non-small cell lung cancer were evaluated to determine if delay in follow-up was associated with clinical upstaging. Results: Three hundred sixty-nine patients with 434 examinations had positive findings; 16% of findings were ultimately diagnosed as lung cancer. In 47% of positive examinations, there was a delay in follow-up (median delay, 104 d), representing 59% (210 d) of Lung-RADS 3 examinations, 35% (64 d) of Lung-RADS 4A examinations, and 40% (34 d) of Lung-RADS 4B/4X examinations (P < 0.001). In the 54 patients diagnosed with non-small cell lung cancer through LCS, delay was associated with increased likelihood of clinical upstaging (P < 0.001). Conclusions: In this study of delay in follow-up after positive LCS findings, we found that nearly half of patients had delays in follow-up and that delay was associated with clinical upstaging in patients whose positive findings represented lung cancer. Further targeted interventions to ensure timely follow-up after positive LCS examination are critical.

Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-κB inflammatory pathway.

Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a variety of DNA-binding transcription factors and has been implicated in many cellular functions; however, physiological studies are limited. Tle1-deficient (Tle1(Δ/Δ)) mice, although grossly normal at birth, exhibit skin defects, lung hypoplasia, severe runting, poor body condition, and early mortality. Tle1(Δ/Δ) mice display a chronic inflammatory phenotype with increased expression of inflammatory cytokines and chemokines in the skin, lung, and intestine and increased circulatory IL-6 and G-CSF, along with a hematopoietic shift toward granulocyte macrophage progenitor and myeloid cells. Tle1(Δ/Δ) macrophages produce increased inflammatory cytokines in response to Toll-like receptor (TLR) agonists and lipopolysaccharides (LPS), and Tle1(Δ/Δ) mice display an enhanced inflammatory response to ear skin 12-O-tetradecanoylphorbol-13-acetate treatment. Loss of Tle1 not only results in increased phosphorylation and activation of proinflammatory NF-κB but also results in decreased Hes1 (hairy and enhancer of split-1), a negative regulator of inflammation in macrophages. Furthermore, Tle1(Δ/Δ) mice exhibit accelerated growth of B6-F10 melanoma xenografts. Our work provides the first in vivo evidence, to our knowledge, that TLE1 is a major counterregulator of inflammation with potential roles in a variety of inflammatory diseases and in cancer progression.