Lung Cancer Screening at a Military Treatment Facility: A Retrospective Review.

INTRODUCTION: Lung cancer is the leading cause of cancer death among men and women, accounting for more fatalities than colon, breast, and prostate cancers combined. Smoking causes about 85% of all lung cancers in the United States and is the single greatest risk factor. In 2013, the US Preventive Services Task Force (USPSTF) published initial guidelines for low-dose computed tomography lung cancer screening (LCS) among patients 55-80 years old, with a 30-pack-year history, who are current smokers or who quit within the previous 15 years. Smoking prevalence is higher among military personnel compared to the civilian population, demonstrating a need for vigilant screening. MATERIALS AND METHODS: A retrospective review of Naval Medical Center San Diego's (NMCSD) LCS data was conducted to examine screening numbers, lung cancer rates, and initial analysis of screening results. Patients were referred for screening if they met the USPSTF criteria. Between September 2013 and September 2018, 962 patients underwent LCS. A total of 1758 examinations were performed, including follow-up and annual surveillance examinations. The American College of Radiology's Lung CT Screening Reporting and Data System (Lung-RADS) was used to classify lung nodules' risk for malignancy. RESULTS: On this initial analysis, 42 enrolled patients received the diagnosis of lung cancer detected by screening. The initial calculated lung cancer rate is 4.4% (42/962) over the 5-year reporting period. The lung cancer rate among those patients with a Lung-RADS score of 3 or 4 was 31% (42/135). Thirty-seven patients were classified as having non-small cell lung cancer (NSCLC), while five were classified as having small cell lung cancer. Of the 37 NSCLC patients, 76% (28/37) were diagnosed at stage I and II, 11% (4/37) were diagnosed at stage III, and 13% (5/37) were diagnosed at stage IV. The total number of years a person smoked was a significant risk factor (P = 0.004), but not pack-years a person smoked (P = 0.052). CONCLUSIONS: These preliminary results demonstrate the success of a Military Treatment Facility (MTF)-based LCS Program in the detection of early stage lung cancer. Earlier stage detection may result in better health outcomes for affected patients. In the population studied, duration of smoking proved to be more significant than pack-years in predicting lung cancer risk. These results validate the newly dedicated resources and continued efforts to strengthen the LCS program at NMCSD and across MTFs.

alphavbeta5 integrin sustains growth of human pre-B cells through an RGD-independent interaction with a basic domain of the CD23 protein.

CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells that has biological activity in both membrane-bound and freely soluble forms, acting via a number of receptors, including integrins. We demonstrate here that soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD-independent interaction with the alphavbeta5 integrin. The integrin recognizes a tripeptide motif in a small disulfide-bonded loop at the N terminus of the lectin head region of CD23, centered around Arg(172), Lys(173), and Cys(174) (RKC). This RKC motif is present in all forms of sCD23 with cytokine-like activity, and cytokine activity is independent of the lectin head, an "inverse RGD" motif, and the CD21 and IgE binding sites. RKC-containing peptides derived from this region of CD23 bind alphavbeta5 and are biologically active. The binding and activity of these peptides is unaffected by inclusion of a short peptide containing the classic RGD sequence recognized by integrins, and, in far-Western analyses, RKC-containing peptides bind to the beta subunit of the alphavbeta5 integrin. The interaction between alphavbeta5 and sCD23 indicates that integrins deliver to cells important signals initiated by soluble ligands without the requirement for interactions with RGD motifs in their common ligands. This mode of integrin signaling may not be restricted to alphavbeta5.