[Show abstract][Hide abstract] ABSTRACT: A recent trial showed the clinical benefit of retreatment with varenicline in subjects failing on the initial treatment, or relapsing after initial success. The objective of this study was to evaluate the cost-effectiveness of retreatment with varenicline compared with other smoking cessation interventions. Methods: A published Markov model was adapted to compare one quit attempt of varenicline followed by retreatment to treatment/retreatment with nicotine replacement therapy (NRT), bupropion or placebo, and with only 1 quit attempt of varenicline. Efficacy was obtained from RCTs. Incidence of smoking-related diseases was based on published data. Cost of therapies and complications was obtained from databases and literature.
[Show abstract][Hide abstract] ABSTRACT: Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low-dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low-dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and a quality assurance plan. The establishment of a central registry, including a biobank and an image bank, and preferably on a European level, is strongly encouraged.
• Lung cancer screening using low dose computed tomography reduces mortality. • Leading US medical societies recommend large scale screening for high-risk individuals. • There are no lung cancer screening recommendations or reimbursed screening programmes in Europe as of yet. • The European Society of Radiology and the European Respiratory Society recommend lung cancer screening within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. • High risk, eligible individuals should be enrolled in comprehensive, quality-controlled longitudinal programmes.
European Radiology 05/2015; 25(9). DOI:10.1007/s00330-015-3697-0 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rationale. It has previously been argued that implicit attitudes towards substance-related cues drive addictive behavior. Nevertheless, it remains an open question whether behavioral markers of implicit attitude activation can be used to predict long-term relapse.
Objectives. The main objective of this study was to examine the relationship between implicit attitudes towards smoking-related cues and long-term relapse in abstaining smokers.
Methods. Implicit attitudes towards smoking-related cues were assessed by means of the Implicit Association Test (IAT) and the Evaluative Priming Task (EPT). Both measures were completed by a group of smokers who volunteered to quit smoking (Patient Group) and a group of non-smokers (Control Group). Participants in the Patient Group completed these measures twice: once prior to smoking cessation and once after smoking cessation. Relapse was assessed by means of short telephone survey, six months after completion of the second test session.
Results. EPT scores obtained prior to smoking cessation were related to long-term relapse and correlated with self-reported nicotine dependence as well as daily cigarette consumption. In contrast, none of the behavioral outcome measures were found to correlate with the IAT scores.
Conclusions. These findings corroborate the idea that implicit attitudes towards substance-related cues are critically involved in long-term relapse. A potential explanation for the divergent findings obtained with the IAT and EPT is provided.
[Show abstract][Hide abstract] ABSTRACT: Low-dose CT screening is recommended for individuals at high risk of developing lung cancer. However, CT screening does not detect all lung cancers: some might be missed at screening, and others can develop in the interval between screens. The NELSON trial is a randomised trial to assess the effect of screening with increasing screening intervals on lung cancer mortality. In this prespecified analysis, we aimed to assess screening test performance, and the epidemiological, radiological, and clinical characteristics of interval cancers in NELSON trial participants assigned to the screening group.
The Lancet Oncology 10/2014; 15(12). DOI:10.1016/S1470-2045(14)70387-0 · 24.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main challenge in CT screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer. Management protocols use thresholds for nodule size and growth rate to determine which nodules require additional diagnostic procedures, but these should be based on individuals' probabilities of developing lung cancer. In this prespecified analysis, using data from the NELSON CT screening trial, we aimed to quantify how nodule diameter, volume, and volume doubling time affect the probability of developing lung cancer within 2 years of a CT scan, and to propose and evaluate thresholds for management protocols.
The Lancet Oncology 10/2014; 15(12). DOI:10.1016/S1470-2045(14)70389-4 · 24.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the diagnostic accuracy of the visual assessment of malignant pleural mesothelioma (MPM) on magnetic resonance (MR) images by using two known visual markers (mediastinal pleural thickness and shrinking of the lung) and a newly introduced one (pleural pointillism).
Materials and methods:
With the approval of the local ethics committee, 100 consecutive patients (mean age, 61.4 years; age range, 18-87 years; 75 men, 25 women) suspected of having MPM pleural abnormalities underwent positron emission tomography/computed tomography and MR imaging, including diffusion-weighted (DW) MR imaging, followed by explorative thoracoscopy or guided biopsy with histopathologic confirmation. Because visual assessment is still the preferred method of image interpretation, the diagnostic accuracy of mediastinal pleural thickening, shrinking lung (hemithorax volume decrease due to fibrosis), and pleural pointillism were examined. Pleural pointillism was denoted by the presence of multiple, hyperintense pleural spots on high-b-value DW images. Histopathologic findings in the surgical specimen served as the reference standard. McNemar tests with Bonferroni correction were used to assess differences in accuracy among the three examined markers.
Of 100 patients, 33 had benign pleural alterations, and 67 had malignant pleural diseases (MPDs); 57 of 67 had MPM. A total of 78 patients received a correct diagnosis (benign vs malignant) on the basis of mediastinal pleural thickening (sensitivity, 81%; specificity, 73%; accuracy, 78%); and 66 patients, on the basis of shrinking lung (sensitivity, 60%; specificity, 79%; accuracy, 66%). The correct diagnosis was indicated on the basis of pleural pointillism in 88 patients (sensitivity, 93%; specificity, 79%; accuracy, 88%).
Visual assessment of pleural pointillism on high-b-value DW images is useful to differentiate MPD from benign alterations, performing substantially better than mediastinal pleural thickness and shrinking lung, and might obviate unnecessary invasive procedures for MPM.
[Show abstract][Hide abstract] ABSTRACT: The efficacy and safety of re-treatment with varenicline in smokers attempting to quit was evaluated in this randomized, double-blind, placebo-controlled, multicenter trial (Australia, Belgium, Canada, Czech Republic, France, Germany, UK and US). Participants were generally-healthy adult smokers (≥10 cigs/day); ≥1 prior quit attempt (≥2 weeks) using varenicline; no quit attempts in ≤3 months; and randomly-assigned (1:1) to 12 weeks' varenicline (N=251) or placebo (N=247) treatment, with individual counseling, plus 40 weeks non-treatment follow-up. Primary efficacy endpoint was carbon monoxide confirmed (≤10 ppm) continuous abstinence rate (CAR) for weeks 9-12, which were 45.0% (varenicline; N=249) versus 11.8% (placebo; N=245; OR=7.08; 95% CI: 4.34, 11.55; P<0.0001). Common varenicline-group adverse events were nausea, abnormal dreams, and headache, with no reported suicidal behavior. Varenicline is effective and well-tolerated in smokers who have previously taken varenicline. Abstinence rates are comparable with rates reported for varenicline-naïve smokers. Trial registration: www.clinicaltrials.gov (NCT01244061). Funding source: Pfizer Inc.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 09 June 2014; doi:10.1038/clpt.2014.124.
[Show abstract][Hide abstract] ABSTRACT: Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools which could improve patient's survival. Recently, breath analysis as a non-invasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOCs) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma in order to stimulate further research in this field.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
The main challenge in computed tomography (CT) screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer. Thresholds for nodule size and growth rate, which determine which nodules require additional diagnostic measures, should be based on the lung cancer probability of the individual.
METHOD AND MATERIALS
The diameter, volume and volume-doubling time (VDT) of 9,681 non-calcified nodules detected in 7,135 participants in the Dutch-Belgian lung cancer screening trial were used to quantify their lung cancer probability. Complete coverage on all lung cancer diagnoses was obtained by linkages with the national cancer registry, for a follow-up of eight years. The probabilities were used to propose and evaluate optimized thresholds for CT-detected nodules.
Lung cancer probability was low in subjects with a nodule volume <100mm³ (≤0.7%) or maximum transverse diameter <5mm (≤0.5%). Moreover, probability in these subjects was not significantly different from that in subjects without nodules (0.4%). Lung cancer probability was intermediate for nodule volumes 100-300mm³ (1.5-5.8%) and diameters 5-10mm (0.9-2.9%); the VDT further stratified the probability: 0.0-0.9% for VDTs>600days, 4.0% for VDTs 400-600days and 6.7-25.0% for VDTs<400days. Lung cancer probability was high for participants with nodule volumes ≥300mm³ (8.9-26.1%) or diameters ≥10mm (11.1-26.2%), even with long VDTs.
Subjects with nodules <100mm³ or <5mm have a lung cancer risk that is not significantly different from that in subjects without nodules and do not require additional evaluation. Individuals with nodules 100-300mm³ or 5-10mm represent an indeterminate subgroup for whom the assessment of VDT is appropriate (<400days warrants diagnostic work-up). However, the risk for subjects with nodules ≥300mm³ or ≥10mm demands immediate diagnostic evaluation.
This study provides detailed and reliable data on the lung cancer probability of subjects with CT-detected nodules stratified by nodule diameter, volume and growth rate. This information can be valuab
Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
[Show abstract][Hide abstract] ABSTRACT: To evaluate the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance (MR) and diffusion-weighted imaging (DWI) sequences for defining benignity or malignancy of solitary pulmonary lesions (SPL).
First, 54 consecutive patients with SPL, clinically staged (CT and PET or integrated PET-CT) as N0M0, were included in this prospective study. An additional 3-Tesla MR examination including DCE and DWI was performed 1 day before the surgical procedure. Histopathology of the surgical specimen served as the standard of reference. Subsequently, this functional method of SPL characterisation was validated with a second cohort of 54 patients.
In the feasibility group, 11 benign and 43 malignant SPL were included. Using the combination of conventional MR sequences with visual interpretation of DCE-MR curves resulted in a sensitivity, specificity and accuracy of 100 %, 55 % and 91 %, respectively. These results can be improved by DWI (with a cut-off value of 1.52 × 10(-3) mm(2)/s for ADChigh) leading to a sensitivity, specificity and accuracy of 98 %, 82 % and 94 %, respectively. In the validation group these results were confirmed.
Visual DCE-MR-based curve interpretation can be used for initial differentiation of benign from malignant SPL, while additional quantitative DWI-based interpretation can further improve the specificity.
• Magnetic resonance imaging is increasingly being used to help differentiate lung lesions. • Solitary pulmonary lesions (SPL) are accurately characterised by combining DCE-MRI and DWI. • Visual DCE-MRI assessment facilitates the diagnostic throughput in patients with SPL. • DWI provides additional information in inconclusive DCE-MRI (type B pattern).
European Radiology 10/2013; 24(2). DOI:10.1007/s00330-013-3053-1 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evaluation of: National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368, 1980-1991 (2013). In 2011, the US NLST trial demonstrated that mortality from lung cancer can be reduced by using low-dose computed tomography (LDCT) screening rather than chest x-ray (CXR) screening. This paper from the US NLST research team focuses on the results of the initial round of LDCT for lung cancer. A total of 53,439 participants were included and randomly assigned to LDCT screening (n = 26,715) or CXR screening (n = 26,724). In total, 27.3% of the participants in the LDCT group and 9.2% in the CXR group had a positive screening result. As a result, 3.8% (LDCT group) and 5.7% (CXR group) of these subjects were diagnosed with lung cancer. The sensitivity (93.8%) and specificity (73.4%) for lung cancer were higher for LDCT compared with CXR screening; 73.5 and 91.3%, respectively.
Journal of Comparative Effectiveness Research 09/2013; 2(5):433-6. DOI:10.2217/cer.13.57 · 0.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. The purpose of this article is to retrospectively evaluate the technical and clinical outcomes of large-bore nitinol stents for treating malignant superior vena cava syndrome. In addition, we analyzed factors potentially influencing the outcome.
MATERIALS AND METHODS. Over a 7-year period, 78 consecutive patients presented with superior vena cava syndrome related to primary lung tumor (n = 62) or malignant lymphadenopathies (n = 16). The factors analyzed were Kishi score at admission, tumor type, and need for an additional balloon-expandable stent.
RESULTS. Technical success was obtained in all but one patient (99%), who presented with a stent migration immediately after insertion. In 17 patients (22%), an additional balloon-expandable stent was needed for complete expansion of the nitinol stent. For patients with symptomatic malignant lymphadenopathies or primary lung tumor, overall survival rates were 50% (n = 8) and 54% (n = 34), respectively, at 6 months and 19% (n = 3) and 34% (n = 21), respectively, at 12 months (p = 0.376). There was no difference in survival as a function of the Kishi score (p = 0.80) or of the placement of an additional balloon-expandable stent (p = 0.35). Finally, reocclusion events were noted in patients both with (n = 1) and without (n = 7) a balloon-expandable stent.
CONCLUSION. Large-bore nitinol stents are highly effective for malignant superior vena cava syndrome. The survival rates of patients with caval vein stenosis due to either the primary tumor or secondary enlarged adenopathies were equal. An additional balloon-expandable stent was required in 22% of cases owing to incomplete expansion of the nitinol stent but was not associated with higher thrombosis rate.
Read More: http://www.ajronline.org/doi/abs/10.2214/AJR.12.9582
American Journal of Roentgenology 09/2013; 201(3):667-74. DOI:10.2214/AJR.12.9582 · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several medical associations recommended lung cancer screening by low-dose computer tomography (LDCT) scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening.In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm(3) and for (part) solid or non-solid nodules with a volume-doubling time <400days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years.458 (6%) of the 7.582 screened participants had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7% after an indeterminate baseline and 48.3% after a positive baseline.The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with LDCT.
European Respiratory Journal 07/2013; 42(6). DOI:10.1183/09031936.00197712 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: RATIONALE: The NELSON trial is with 15,822 participants the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening and an increasing length of the screening interval are particular features of the NELSON trial. OBJECTIVES: To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of the screen-detected lung cancers, and to compare this across screening rounds, between genders and with other screening trials METHODS: All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the genders and with other screening trials. MEASUREMENTS AND MAIN RESULTS: In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. 70.8% of the lung cancers were diagnosed at stage I, 8.1% at stage IIIB-IV and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology or tumor localization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared to other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV. CONCLUSIONS: Despite stringent criteria for a positive screening, an increasing length of the screening interval and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is a prerequisite for the effectiveness of our screening strategy.
American Journal of Respiratory and Critical Care Medicine 01/2013; 187(8). DOI:10.1164/rccm.201209-1651OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
To evaluate the diagnostic accuracy of dynamic contrast enhanced (DCE) magnetic resonance (MR) and diffusion weighted imaging (DWI) sequences for diagnosing of preoperative pulmonary nodules and masses. A simplified MR examination evaluation may lead to a better characterization of lung lesions.
METHOD AND MATERIALS
Sixty consecutive preoperative patients aged 61.3 ± 29.3 years (39 males and 21 females) and staged on PET/CT as N0M0 were included in this prospective study. We performed an additional MR including diffusion- and perfusion-weighted imaging one day before the surgical procedure. PET/CT staging occurred in the clinical routine patient diagnosis and only if integrated PET-CT available (22/60 in 45%), for study purposes each lesion was quantitatively measured by a contrast ratio of maximal standard uptake value (SUVmax-CR) between the lesion and the contralateral lung. All MR images were interpreted independently by 2 experienced radiologists. Afterwards they were evaluated in consensus and an interpreting flowchart was distillated based on statistical principles. Histopathology of the surgical specimen served as standard of reference.
Sixty-six lung lesions in this cohort -17 benign and 49 malignant lung nodules/masses- had a diameter that varied from 3 to 62 mm (mean 16.2 mm). Only two lesions on DWI could not be determined, because of high noise level. The sensitivity, specificity and accuracy of PET/CT are 87.0%, 31.3% and 74.3%. Using the conventional MR sequences with visual interpretation of DCE-MR curves gives 96.3%, 68,8% and 90.0%. This can be augmented by additional interpretation of quantitiative ADC values (with a cut-off value of 1.52 x10^(-3) mm²/s of ADCaverage and 1.3 x10^(-3) mm²/s of ADChigh) leading to 96.3%, 100% and 97.1% respectively.
Visual DCE-MR based curve interpretation can be used as first separation of benign from malignant lesions, while further quantitiative DWI-based interpretation can lead to a higher accuracy.
DCE-MRI and DWI might help to provide a more accurate diagnosis in preoperative patients suspected for malignant pulmonary nodules and masses avoiding invasive procedures or follow-up examinations.
Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012