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Inflammatory status and lung function predict mortality in lung cancer screening participants.

ABSTRACT: Low-dose computed tomography (LDCT) screening trials have based their risk selection algorithm on age and tobacco exposure, but never on pulmonary risk-related biomarkers. In the present study, the baseline inflammatory status, measured by C-reactive protein (CRP) level, and lung function, measured by forced expiratory volume in 1?s (FEV1), were tested as independent predictors of all-cause mortality in LDCT-screening participants. Between 2000 and 2010, 4413 volunteers were enrolled in two LDCT-screening trials, with evaluable baseline CRP and FEV1 values: 2037 were included in the discovery set and 2376 were included in the validation set. The effect of low FEV1 or high CRP alone or combined was evaluated by Kaplan-Meier mortality curves and hazard ratio (HR) with 95% confidence interval (CI) by fitting Cox proportional hazards models. The overall mortality risk was significantly higher in participants with FEV1 of up to 90% (HR: 2.13, CI: 1.43-3.17) or CRP more than 2?mg/l (HR: 3.38, CI: 1.60-3.54) and was still significant in the fully adjusted model. The cumulative 10-year probability of death was 0.03 for participants with FEV1 of more than 90% and CRP up to 2?mg/l, 0.05 with only FEV1 of up to 90% or CRP above 2?mg/l, and 0.12 with FEV1 of up to 90% and CRP above 2?mg/l. This predictive performance was confirmed in the two external validation cohorts with 10-year mortality rates of 0.06, 0.12, and 0.14, and 0.03, 0.07, and 0.14, respectively. Baseline inflammatory status and lung function reduction are independent predictors of all-cause long-term mortality in LDCT-screening participants. CRP and FEV1 could be used to select higher-risk individuals for future LDCT screening and preventive programs.

SUBMITTER: Pastorino U

PROVIDER: S-EPMC6012047 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Inflammatory status and lung function predict mortality in lung cancer screening participants.

Pastorino Ugo U Morelli Daniele D Marchianò Alfonso A Sestini Stefano S Suatoni Paola P Taverna Francesca F Boeri Mattia M Sozzi Gabriella G Cantarutti Anna A Corrao Giovanni G

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 20180701 4

Low-dose computed tomography (LDCT) screening trials have based their risk selection algorithm on age and tobacco exposure, but never on pulmonary risk-related biomarkers. In the present study, the baseline inflammatory status, measured by C-reactive protein (CRP) level, and lung function, measured by forced expiratory volume in 1 s (FEV1), were tested as independent predictors of all-cause mortality in LDCT-screening participants. Between 2000 and 2010, 4413 volunteers were enrolled in two LDCT ...[more]

PMID: 28333763

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Project description:Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations.We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385.Our cohort consisted of 26?231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19?066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26?231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100?000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17-211·93] per 100?000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18?121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26?231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100?000 person-years to 212·14 [186·80-239·96]) over the course of the trial.Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted.None.

Project description:OBJECTIVES:We investigated if psychosocial status, sociodemographics and smoking status affected non-attendance in the control group in the randomised Danish Lung Cancer Screening Trial (DLCST). DESIGN AND SETTING:This study was an observational study nested in the DLCST. Due to large non-attendance in the control group in the second screening round we made an additional effort to collect questionnaire data from non-attenders in this group in the third screening round. We used a condition-specific questionnaire to assess psychosocial status. We analysed the differences in psychosocial status in the third and preceding rounds between non-attenders and attenders in the control group in multivariable linear regression models adjusted for sociodemographics and smoking status reported at baseline. Differences in sociodemographics and smoking status were analysed with ?2 tests (categorical variables) and t-tests (continuous variables). PRIMARY OUTCOME MEASURE:Primary outcome was psychosocial status. PARTICIPANTS:All control persons participating in the third screening round in the DLCST were included. RESULTS:Non-attenders in the third round had significantly worse psychosocial status than attenders in the scales: 'behaviour' 0.77 (99% CI 0.18 to 1.36), 'self-blame' 0.59 (99% CI 0.14 to 1.04), 'focus on airway symptoms' 0.22 (99% CI 0.08 to 0.36), 'stigmatisation' 0.51 (99% CI 0.16 to 0.86), 'introvert' 0.56 (99% CI 0.23 to 0.89) and 'harms of smoking' 0.35 (99% CI 0.11 to 0.59). Moreover, non-attenders had worse scores than attendees in the preceding screening rounds. Non-attenders also reported worse sociodemographics at baseline. CONCLUSIONS:Non-attenders had a significantly worse psychosocial status and worse sociodemographics compared with attenders. The results of our study contribute with evidence of non-response and attrition driven by psychosocial status, which in turn may be influenced by the screening intervention itself. This can be used to adjust cancer screening trial results for bias due to differential non-attendance. TRIAL REGISTRATION NUMBER:Clinicaltrials.gov Protocol Registration System (NCT00496977).

Project description:ImportanceAspirin use has been associated with reduced risk of cancer mortality, particularly of the colorectum. However, aspirin efficacy may be influenced by biological characteristics, such as obesity and age. With the increasing prevalence of obesity and conflicting data regarding the effect of aspirin in older adults, understanding the potential association of aspirin use with cancer mortality according to body mass index (BMI) and age is imperative.ObjectivesTo investigate the association of aspirin use with risk of all-cause, any cancer, gastrointestinal (GI) cancer, and colorectal cancer (CRC) mortality among older adults and to perform an exploratory analysis of the association of aspirin use with mortality stratified by BMI.Design, setting, participantsThis cohort study evaluated aspirin use among participants aged 65 years and older in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial at baseline (November 8, 1993, to July 2, 2001) and follow-up (2006-2008). Analysis began in late 2018 and was completed in September 2019.Main outcomes and measuresAll-cause, any cancer, GI cancer, or CRC mortality. Multivariable hazard ratios (HRs) and 95% CIs were calculated using time-varying Cox proportional hazards regression modeling, adjusting for additional factors.ResultsA total of 146 152 individuals (mean [SD] age at baseline, 66.3 [2.4] years; 74 742 [51.1%] women; 129 446 [88.6%] non-Hispanic white) were included in analysis. The median (interquartile range) follow-up time was 12.5 (8.7-16.4) years, encompassing 1 822 164 person-years. Compared with no use, aspirin use 1 to 3 times per month was associated with reduced risk of all-cause mortality (HR, 0.84; 95% CI, 0.80-0.88; P < .001) and cancer mortality (HR, 0.87; 95% CI, 0.81-0.94; P < .001). Aspirin use 3 or more times per week was associated with decreased risk of mortality of all causes (HR, 0.81; 95% CI, 0.80-0.83; P < .001), any cancer (HR, 0.85; 95% CI, 0.81-0.88; P < .001), GI cancer (HR, 0.75; 95% CI, 0.66-0.84; P < .001), and CRC (HR, 0.71; 95% CI, 0.61-0.84; P < .001). When stratified by BMI (calculated as weight in kilograms divided by height in meters squared), aspirin use 3 or more times per week among individuals with BMI 20 to 24.9 was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.78-0.85; P < .001) and any cancer mortality (HR, 0.86; 95% CI, 0.79-0.82; P < .001). Among individuals with BMI 25 to 29.9, aspirin use 3 or more times per week was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.79-0.85; P < .001), any cancer mortality (HR, 0.86; 95% CI, 0.81-0.91; P < .001), GI cancer mortality (HR, 0.72; 95% CI, 0.60-0.86; P < .001), and CRC mortality (HR, 0.66; 95% CI, 0.51-0.85; P = .001).Conclusions and relevanceIn this cohort study, aspirin use 3 or more times per week was associated with a reduction in all-cause, cancer, GI cancer and CRC mortality in older adults.

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Inflammatory status and lung function predict mortality in lung cancer screening participants.

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Inflammatory status and lung function predict mortality in lung cancer screening participants.

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