Smoking, Smoking Cessation, and Lung Cancer Screening in the NELSON Trial

More than one billion people around the world currently smoke tobacco. The use of tobacco kills more than 5 million people yearly. If this trend continues, it is expected that more than 8 million people will die annually from tobacco-related diseases by 2030 and more than 1 billion people during the 21st century. The potential health effects of smoking were predicted as early as the 19th century. Nevertheless, it was not until the 1950s that study results associated smoking with lung cancer. Nowadays, it is known that tobacco smoke consists of many chemicals, of which more than 60 are confirmed or suspected carcinogenic substances, and that it affects nearly every organ in the body. Smoking is a risk factor for six of the eight leading causes of death worldwide, with the top three: 1) lung cancer, 2) Chronic Obstructive Pulmonary Diseases, and 3) cardiovascular diseases.5 The chance that a lifelong smoker will die prematurely from a tobacco-related disease is about 50%, and smokers who continued smoking will die on average ten years earlier than lifelong non-smokers. For these reasons, the use of tobacco is the most important cause of preventable disease and premature death worldwide. The economic burden of tobacco use has been estimated at US$500 billion globally and US$ 98-103 billion for the European Union

Coronary artery calcium scoring in individuals at risk for coronary artery disease:current status and future perspectives

The aim of this review is to provide clinicians with an overview of the role of coronary artery calcium (CAC) scoring across the spectrum ranging from asymptomatic individuals to chronic chest pain patients. We will briefly introduce the technical background of CAC scoring, summarize the major guidelines per type of patient at risk and discuss latest research with respect to CAC. Finally, the reader should be able to determine when CAC scoring is indicated or may be of added value

Projected effectiveness of lung cancer screening and concurrent smoking cessation support in the Netherlands

Background: The NELSON trial demonstrated a 24% intention-to-screen reduction in lung cancer mortality from regular screening with low-dose computed tomography. Implementation efforts in Europe are ongoing, but still await country-specific and NELSON-adapted estimates of the benefits and harms of screening. Methods: We use the MISCAN-Lung microsimulation model, calibrated to individual-level outcomes from the NELSON trial, to estimate the effectiveness under 100% compliance of biennial lung cancer screening with concomitant smoking cessation support for Dutch cohorts 1942–1961. The model simulates smoking behaviour, lung cancer incidence and the effects of screening and smoking cessation on lung- and other-cause mortality. Findings: We find biennial screening with eligibility criteria equal to those of the 4-IN-THE-LUNG-RUN implementation trial to reduce lung cancer mortality by 16.9% among the eligible population, equivalent to 1076 LC deaths prevented per year in the next two decades. Eligible individuals constitute 21.5% of the cohorts studied, and stand to face 61% of the projected lung cancer mortality burden in the absence of screening. 10.3 life-years are gained per prevented LC death, for 14.9 screens per life year gained. Concomitant smoking cessation interventions may increase the expected gains in life years from screening by up to 20%. Interpretation: Policy makers should imminently consider the implementation of lung cancer screening in Europe, paired with effective smoking cessation interventions. Smoking cessation interventions on their own are not estimated to yield a gain in remaining life expectancy of the magnitude offered by even a single CT screen. Funding: European Union Horizon 2020 grant 848294: 4-IN-THE-LUNG-RUN.</p

Projected effectiveness of lung cancer screening and concurrent smoking cessation support in the Netherlands

Background: The NELSON trial demonstrated a 24% intention-to-screen reduction in lung cancer mortality from regular screening with low-dose computed tomography. Implementation efforts in Europe are ongoing, but still await country-specific and NELSON-adapted estimates of the benefits and harms of screening. Methods: We use the MISCAN-Lung microsimulation model, calibrated to individual-level outcomes from the NELSON trial, to estimate the effectiveness under 100% compliance of biennial lung cancer screening with concomitant smoking cessation support for Dutch cohorts 1942–1961. The model simulates smoking behaviour, lung cancer incidence and the effects of screening and smoking cessation on lung- and other-cause mortality. Findings: We find biennial screening with eligibility criteria equal to those of the 4-IN-THE-LUNG-RUN implementation trial to reduce lung cancer mortality by 16.9% among the eligible population, equivalent to 1076 LC deaths prevented per year in the next two decades. Eligible individuals constitute 21.5% of the cohorts studied, and stand to face 61% of the projected lung cancer mortality burden in the absence of screening. 10.3 life-years are gained per prevented LC death, for 14.9 screens per life year gained. Concomitant smoking cessation interventions may increase the expected gains in life years from screening by up to 20%. Interpretation: Policy makers should imminently consider the implementation of lung cancer screening in Europe, paired with effective smoking cessation interventions. Smoking cessation interventions on their own are not estimated to yield a gain in remaining life expectancy of the magnitude offered by even a single CT screen. Funding: European Union Horizon 2020 grant 848294: 4-IN-THE-LUNG-RUN.</p

Multi-Modality Imaging for Prevention of Coronary Artery Disease and Myocardial Infarction in the General Population:Ready for Prime Time?

Cardiovascular disease (CVD) remains a leading cause of death and disability worldwide. Acute myocardial infarction (AMI) causes irreversible myocardial damage, heart failure, life-threatening arrythmias and sudden cardiac death (SCD), and is a main driver of CVD mortality and morbidity. To control the forecasted increase in CVD burden for both the individual and society, improved strategies for the prevention of AMI and SCD are required. Current prevention of AMI and SCD is directed towards risk-modifying interventions, guided by risk assessment using clinical risk prediction scores (CRPSs) and the coronary artery calcium score (CACS). Early detection of more advanced coronary artery disease (CAD), beyond risk assessment by CRPSs or CACS, is a promising strategy to allow personalized treatment for the improved prevention of AMI and SCD in the general population. We review evidence for further testing, beyond CRPSs and CACS, and therapies focusing on promising targets, including subclinical obstructive CAD, high-risk plaques, and silent myocardial ischemia. We also evaluate the potential of multi-modality imaging to enhance the conduction of adequately powered trials to provide high-quality evidence on the impact of add-on tests and therapies in the prevention of AMI and SCD in asymptomatic individuals. To conclude, we discuss the occurrence of AMI and SCD in individuals currently estimated to be at "low-risk" by the current strategy based on CRPSs, and methods to improve prevention of AMI and SCD in this "low-risk" population

New Fissure-Attached Nodules in Lung Cancer Screening:A Brief Report From The NELSON Study

Introduction: In incidence lung cancer screening rounds, new pulmonary nodules are regular findings. They have a higher lung cancer probability than baseline nodules. Previous studies have shown that baseline perifissural nodules (PFNs) represent benign lesions. Whether this is also the case for incident PFNs is unknown. This study evaluated newly detected nodules in the Dutch-Belgian randomized-controlled NELSON study with respect to incidence of fissure-attached nodules, their classification, and lung cancer probability. Methods: Within the NELSON trial, 7557 participants underwent baseline screening between April 2004 and December 2006. Participants with new nodules detected after baseline were included. Nodules were classified based on location and attachment. Fissure-attached nodules were re-evaluated to be classified as typical, atypical, or non-PFN by two radiologists without knowledge of participant lung cancer status. Results: One thousand four hundred eighty-four new nodules were detected in 949 participants (77.4% male, median age 59 years [interquartile range: 55–63 years]) in the second, third, and final NELSON screening round. Based on 2-year follow-up or pathology, 1393 nodules (93.8%) were benign. In total, 97 (6.5%) were fissure-attached, including 10 malignant nodules. None of the new fissure-attached malignant nodules was classified as typical or atypical PFN. Conclusions: In the NELSON study, 6.5% of incident lung nodules were fissure-attached. None of the lung cancers that originated from a new fissure-attached nodule in the incidence lung cancer screening rounds was classified as a typical or atypical PFN. Our results suggest that also in the case of a new PFN, it is highly unlikely that these PFNs will be diagnosed as lung cancer

Relationship between the number of new nodules and lung cancer probability in incidence screening rounds of CT lung cancer screening:The NELSON study

textabstractBackground: New nodules are regularly found after the baseline round of low-dose computed tomography (LDCT) lung cancer screening. The relationship between a participant's number of new nodules and lung cancer probability is unknown. Methods: Participants of the ongoing Dutch-Belgian Randomized Lung Cancer Screening (NELSON) Trial with (sub)solid nodules detected after baseline and registered as new by the NELSON radiologists were included. The correlation between a participant's new nodule count and the largest new nodule size was assessed using Spearman's rank correlation. To evaluate the new nodule count as predictor for new nodule lung cancer together with largest new nodule size, a multivariable logistic regression analysis was performed. Results: In total, 705 participants with 964 new nodules were included. In 48% (336/705) of participants no nodule had been found previously during baseline screening and in 22% (154/705) of participants >1 new nodule was detected (range 1–12 new nodules). Eventually, 9% (65/705) of the participants had lung cancer in a new nodule. In 100% (65/65) of participants with new nodule lung cancer, the lung cancer was the largest or only new nodule at initial detection. The new nodule lung cancer probability did not differ significantly between participants with 1 (10% [56/551], 95%CI 8–13%) or >1 new nodule (6% [9/154], 95%CI 3–11%, P =.116). An increased number of new nodules positively correlated with a participant's largest nodule size (P < 0.001, Spearman's rho 0.177). When adjusted for largest new nodule size, the new nodule count had a significant negative association with lung cancer (odds ratio 0.59, 0.37–0.95, P =.03). Conclusion: A participant's new nodule count alone only has limited association with lung cancer. However, a higher new nodule count correlates with an increased largest new nodule size, while the lung cancer probability remains equivalent, and may improve lung cancer risk prediction by size only

Early detection of obstructive coronary artery disease in the asymptomatic high-risk population:objectives and study design of the EARLY-SYNERGY trial

Background: Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively. Methods: EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life. Conclusions: EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes