To describe the rational and design of a population-based comparative study. The objective of the study is to assess the screening performance of volume-based management of CT-detected lung nodule in ...comparison to diameter-based management, and to improve the effectiveness of CT screening for chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), in addition to lung cancer, based on quantitative measurement of CT imaging biomarkers in a Chinese screening setting.
A population-based comparative study is being performed, including 10,000 asymptomatic participants between 40 and 74 years old from Shanghai urban population. Participants in the intervention group undergo a low-dose chest and cardiac CT scan at baseline and 1 year later, and are managed according to NELCIN-B3 protocol. Participants in the control group undergo a low-dose chest CT scan according to the routine CT protocol and are managed according to the clinical practice. Epidemiological data are collected through questionnaires. In the fourth year from baseline, the diagnosis of the three diseases will be collected.
The unnecessary referral rate will be compared between NELCIN-B3 and standard protocol for managing early-detected lung nodules. The effectiveness of quantitative measurement of CT imaging biomarkers for early detection of lung cancer, COPD and CVD will be evaluated.
We expect that the quantitative assessment of the CT imaging biomarkers will reduce the number of unnecessary referrals for early detected lung nodules, and will improve the early detection of COPD and CVD in a Chinese urban population.
ClinicalTrials.gov, NCT03988322. Registered on 14 June 2019.
Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic ...procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15–20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40–50%.
Aims
To identify subgroups of patients with type 2 diabetes mellitus (T2DM) following distinct trajectories of HbA1c after insulin initiation and explore underlying differences in clinical ...characteristics.
Materials and methods
A cohort study was conducted in patients with T2DM initiating insulin in 2007–2013 with a follow‐up of 2 to 4 years. Data were collected from the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was subgroups with different trajectories of HbA1c patterns after insulin initiation, as identified by latent class growth modeling. Differences between subgroups were tested using one‐way ANOVA, Kruskal‐Wallis or chi‐square tests, where appropriate.
Results
From 1459 patients, three subgroups with distinct HbA1c patterns were identified. Group 1 (8%) initially showed a moderate decrease followed by an increase in HbA1c 2 years later, despite receiving more comedication. Group 2 (84%) showed a stable decrease. Group 3 (8%) had a high initial level of HbA1c and a rapid decline within the first year, followed by a slow increase thereafter. Group 1 patients were on average 6–7 years younger than patients in groups 2 and 3 and were more likely to receive sulfonylureas than Group 3 patients. Group 3 patients had a shorter diabetes duration and were less well‐controlled for HbA1c, systolic blood pressure and LDL‐cholesterol at insulin initiation.
Conclusions
Most patients showed a stable HbA1c response, but one out of six patients showed either a poor response, or a rapid initial response only after insulin initiation. Response patterns were associated with age, diabetes duration and risk‐factor controls at the time of insulin initiation.
Self-reported cancer has been validated with heterogeneous results across populations. The aim was to assess the validity of self-reported cancer in the Lifelines population-based cohort and to ...search for explanations for not reporting cancer.
Data from adult participants (n = 152,780) from Lifelines was linked to the Dutch-Nationwide pathology databank (PALGA), which has nearly 100% coverage of cancer diagnoses in the Netherlands and is considered as the gold standard for ascertainment of cancer diagnosis in this study. Sensitivity and positive predictive value (PPV) for self-reported cancers -reported as hand-written free text- were described. Logistic regressions analyses were performed to evaluate whether socio-demographic factors were associated with the presence of self-reported cancer when there was a diagnosis in PALGA.
6611 (4.50%) participants had at least one self-reported diagnosis of cancer, where 9960 (6.97%) participants had at least one cancer diagnosis in PALGA. The sensitivity of self-reported cancer was 64.68% 95%CI:63.71–65.66, and 70.18% 95%CI:68.83–71.56 after excluding skin and cervical cancers. Skin and cervical cancers represented 61.24% of non-self-reported cancers. The overall PPV was 97.45% 95%CI:97.45–97.81, and 97.33% 95%CI:96.72–97.82 after the exclusion of skin and cervical cancers. Participants who did not self-report their cancer were more likely to be male, had longer time since diagnosis and lower educational level.
Overall, the reports of cancer in Lifelines have a high positive predictive value and moderate sensitivity. One third of the cancers were not reported, mainly skin and cervical cancers. Male participants, those with a lower educational level and those with longer time since diagnosis were less likely to self-report a diagnosed cancer.
•Self-reported cancers in the Lifelines population-based cohort have high positive predictive value and moderate sensitivity.•Skin and cervical cancers were the main sources of discrepancies between self-reports and the gold standard source.•Males, those with a lower educational level and longer time since diagnosis were less likely to self-report their cancer.
Immune checkpoint inhibitors (ICIs) are increasingly being used in non-small-cell lung cancer (NSCLC), yet biomarkers predicting their benefit are lacking. We evaluated if on-treatment changes of ...circulating tumor DNA (ctDNA) from ICI start (t
) to after two cycles (t
) assessed with a commercial panel could identify patients with NSCLC who would benefit from ICI.
The molecular ctDNA response was evaluated as a predictor of radiographic tumor response and long-term survival benefit of ICI. To maximize the yield of ctDNA detection, de novo mutation calling was performed. Furthermore, the impact of clonal hematopoiesis (CH)-related variants as a source of biologic noise was investigated.
After correction for CH-related variants, which were detected in 75 patients (44.9%), ctDNA was detected in 152 of 167 (91.0%) patients. We observed only a fair agreement of the molecular and radiographic response, which was even more impaired by the inclusion of CH-related variants. After exclusion of those, a ≥ 50% molecular response improved progression-free survival (10
2 months; hazard ratio HR, 0.55; 95% CI, 0.39 to 0.77;
.0011) and overall survival (18.4
5.9 months; HR, 0.44; 95% CI, 0.31 to 0.62;
< .0001) compared with patients not achieving this end point. After adjusting for clinical variables, ctDNA response and
/
mutations (HR, 2.08; 95% CI, 1.4 to 3.0;
< .001) remained independent predictors for overall survival, irrespective of programmed death ligand-1 expression. A landmark survival analysis at 2 months (n = 129) provided similar results.
On-treatment changes of ctDNA in plasma reveal predictive information for long-term clinical benefit in ICI-treated patients with NSCLC. A broader NSCLC patient coverage through de novo mutation calling and the use of a variant call set excluding CH-related variants improved the classification of molecular responders, but had no significant impact on survival.
Aim: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score ...is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. Methods: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). Results: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6–12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17–1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2–25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24–1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. Conclusions: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.
To develop an imaging reporting system for the classification of 3 adenocarcinoma subtypes of computed tomography (CT)-detected subsolid pulmonary nodules (SSNs) in clinical patients.
Between ...November 2011 and October 2017, 437 pathologically confirmed SSNs were retrospectively identified. SSNs were randomly divided 2:1 into a training group (291 cases) and a testing group (146 cases). CT-imaging characteristics were analyzed using multinomial univariable and multivariable logistic regression analysis to identify discriminating factors for the 3 adenocarcinoma subtypes (pre-invasive lesions, minimally invasive adenocarcinoma, and invasive adenocarcinoma). These factors were used to develop a classification and regression tree model. Finally, an SSN Imaging Reporting System (SSN-IRS) was constructed based on the optimized classification model. For validation, the classification performance was evaluated in the testing group.
Of the CT-derived characteristics of SSNs, qualitative density (nonsolid or part-solid), core (non-core or core), semantic features (pleural indentation, vacuole sign, vascular invasion), and diameter of solid component (≤6 mm or >6 mm), were the most important factors for the SSN-IRS. The total sensitivity, specificity, and diagnostic accuracy of the SSN-IRS was 89.0% (95% confidence interval CI, 84.8%-92.4%), 74.6% (95% CI, 70.8%-78.1%), and 79.4% (95% CI, 76.5%-82.0%) in the training group and 84.9% (95% CI, 78.1%-90.3%), 68.5% (95% CI, 62.8%-73.8%), and 74.0% (95% CI, 69.6%-78.0%) in the testing group, respectively.
The SSN-IRS can classify 3 adenocarcinoma subtypes using CT-based characteristics of subsolid pulmonary nodules. This classification tool can help clinicians to make follow-up recommendations or decisions for surgery in clinical patients with SSNs.
It is essential to identify the subsolid nodules subtype preoperatively to select the optimal treatment algorithm. We developed and validated an imaging reporting system using a classification and regression tree model that based on computed tomography imaging characteristics (291 cases in training group, 146 cases in testing group). The model showed high sensitivity and accuracy of classification. Our model can help clinicians to make follow-up recommendations or decisions for surgery for clinical patients with a subsolid nodule.
Low-dose computed tomography (LDCT) lung cancer screening often refers individuals to unnecessary examinations. This study aims to compare the European Position Statement (EUPS) and National ...Comprehensive Cancer Network (NCCN) protocols in management of participants at baseline screening round.
LDCT lung cancer screening was prospectively performed in a Chinese asymptomatic population aged 40-74 years. A total of 1,000 consecutive baseline LDCT scans were read twice independently. All screen-detected lung nodules by the first reader were included. The first reader manually measured the diameter of lung nodules (NCCN protocol), and the second reader semi-automatically measured the volume and diameter (EUPS volume and diameter protocols). The protocols were used to classify the participants into three management groups: next screening round, short-term repeat LDCT scan and referral to a pulmonologist. Groups were compared using Wilcoxon test for paired samples. Number of lung cancers by protocols was provided.
Of the 1,000 participants (61.4±6.7 years old), 168 lung nodules in 124 participants were visually detected and manually measured in the first reading, and re-measured semi-automatically. Applying the NCCN protocol, EUPS volume and diameter protocol, the proportion of referrals among all participants was 0.6%, 1.9%, and 1.4%, respectively. The proportion of short-term repeat scans was 4.5%, 9.7% and 4.5%, respectively. Among the 10 lung cancer patients, one would have been diagnosed earlier if the EUPS volume protocol would have been followed.
In a first round screening in a Chinese general population, the lower threshold for referral in the EUPS protocol as compared to the NCCN protocol, leads to more referrals to a pulmonologist, with the potential of earlier cancer diagnosis. The EUPS volume protocol recommends fewer participants to short-term repeat LDCT scan than the EUPS diameter protocol. Follow-up studies should show the impact of both protocols on (interval) cancer diagnosis.
Background: Performance measures are used for assessing quality of care. Higher performance shown by these measures is expected to reflect better care, but little is known whether they predict better ...patient outcomes. Objective: To assess the predictive value of performance measures of glucose management on glycemie control, and evaluate the impact of patient characteristics on this association. Research Design: Cohort study (2007-2009). Subjects: A total of 15,454 type 2 diabetes patients (mean age, 66.5 y; 48% male) from the GIANTT cohort. Measures: We included performance measures assessing frequency of HbAlc monitoring, glucose-lowering treatment status, and treatment intensification. Associations between performance and glycemie control were tested using multivariate linear regression adjusted for confounding, reporting estimated differences in HbAlc with 95% confidence intervals (CI). Impact of patient characteristics was examined through interactions. Results: Annual HbAlc monitoring was associated with better glycemie control when compared with no such monitoring (HbAlc -0.29%; 95% CI -0.37, -0.22). This association lost significance in patients with lower baseline HbAlc, older age, and without macrovascular comorbidity. Treatment status was associated with better glycemie control only in patients with elevated baseline HbAlc. Treatment intensification after elevated HbAlc levels was associated with better glycemie control compared with no intensification (HbA1c -0.21; 95% CI -0.26, -0.16). Conclusions: Performance measures of annual HbA1c monitoring and of treatment intensification did predict better patient outcomes, whereas the measure of treatment status did not. Predictive value of annual monitoring and of treatment status varied across patient characteristics, and it should be used with caution when patient characteristics cannot be taken into account.
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