Asbestos-exposed Population Research Articles

P1.14-02 Validation of Lung Cancer Risk Prediction Models in an Asbestos Exposed Population

P1.14-02 Validation of Lung Cancer Risk Prediction Models in an Asbestos Exposed Population

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the ‘test, re-test’ principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

OA13.06 Changing Patterns of Lung Cancer Histology in an Asbestos Exposed Population

Asbestos is a widely recognised lung carcinogen. Exposure to both asbestos and cigarette smoke has a synergistic effect on the risk of developing lung cancer. It is not known if the histology of asbestos-related lung cancer has changed over time, as has been observed with non-asbestos-related lung cancer.

Cost-Effectiveness of an Organized Lung Cancer Screening Program for Asbestos-Exposed Subjects.

Simple SummaryLung cancer screening experiments in smokers are underway in Europe, and data in populations with other risk factors for lung cancer, such as asbestos exposure, are expected. Our original article yielded a cost-effectiveness analysis of a lung cancer screening program in a population exposed to asbestos, based on the data from National Lung Cancer Screening trial and a French asbestos-exposed cohort (ARDCO cohort). Individual data from 14,218 subjects in the ARDCO cohort, followed for 20 years (2002–2022), have allowed several screening models to be established according to exposure level, smoking status and presence of radiological signs of asbestos exposure. For the whole cohort, an annual screening programme is not cost-effective, while screening every 2 years for smokers with high asbestos-exposure and subjects with asbestosis is cost-effective. This analysis has never been reported in the literature and could help in the establishment of inclusion criteria for future experiments in this population.Background: The National Lung Screening Trial (NLST) and NELSON study opened the debate on the relevance of lung cancer (LC) screening in subjects exposed to occupational respiratory carcinogens. This analysis reported the incremental cost-effectiveness ratios (ICER) of an organized LC screening program for an asbestos-exposed population. Methods: Using Markov modelization, individuals with asbestos exposure were either monitored without intervention or annual low-dose thoracic computed-tomography (LDTCT) scan LC screening. LC incidence came from a prospective observational cohort of subjects with occupational asbestos exposure. The intervention parameters were those of the NLST study. Utilities and LC-management costs came from published reports. A sensitivity analysis evaluated different screening strategies. Results: The respective quality-adjusted life year (QALY) gain, supplementary costs and ICER [95% confidence interval] were: 0.040 [0.010–0.065] QALY, 6900 [3700–11,800] € and 170,000 [75,000–645,000] €/QALY for all asbestos-exposed subjects; and 0.144 [0.071–0.216] QALY, 13,000 [5700–26,800] € and 90,000 [35,000–276,000] €/QALY for smokers with high exposure. When screening was based on biennial LDTCT scans, the ICER was 45,000 [95% CI: 15,000–116,000] €/QALY. Conclusions: Compared to the usual ICER thresholds, biennial LDTCT scan LC screening for smokers with high occupational exposure to asbestos is acceptable and preferable to annual scans.

Occupations and geographical distribution of mesothelioma in Switzerland 1989–2018 – record linkage of an asbestos-exposed population with the Swiss National Cohort

We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases. Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved. Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus. It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland.

Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network.

Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as "breath testing" are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes

ABSTRACTTwo of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an “asbestos-resistant exposed population”. A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC “genetic signature” may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.

Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies.

Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies. Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population. Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion. This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis. The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

Correlation of ultra-low dose chest CT findings with physiologic measures of asbestosis.

The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Participants were 92% male with a median age of 73.0years. CT dose index volume was between 0.6 and 1.8mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1second (FEV1) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis. • Interobserver agreement for the ILD score using prone ULDCT is good. • Prone ULDCT appearances of ILD correlate with changes in spirometric observations. • Prone ULDCT appearances of ILD correlate strongly with changes in gas transfer. • Prone ULDCT may provide sufficient radiological evidence to inform the diagnosis of asbestosis.

Current investigations on the utilization of soluble mesothelin-related protein in asbestos-exposed population's health surveillance

Current investigations on the utilization of soluble mesothelin-related protein in asbestos-exposed population's health surveillance

Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population.

This study investigated the mesothelin (MSLN) methylation and its relationship with soluble mesothelin-related protein (SMRP) levels in participants stratified by asbestos exposure scenarios and benign asbestos-related diseases (ARDs). The presence of benign ARDs was confirmed through chest X-ray and the asbestos exposure history was obtained using a standardized questionnaire in this study, including 262 participants. Sera SMRP were measured using MESOMARK, and MSLN methylation in genomic DNA extracted from whole blood was detected by real-time methylation-specific PCR. Covariates were compared with SMRP concentrations using correlation analysis and the potential covariates affecting SMRP were determined by multiple linear regression analysis, and the distribution of methylation status was analyzed by Chi-square test. There was a trend toward elevation of SMRP values in healthy individuals exposed to asbestos as compared with those without asbestos exposure. The highest median level of SMRP was 1.3nM in subjects with asbestosis, followed by cases with pleura plaque and asbestosis (1.2nM), pleura plaque (0.9nM), healthy subjects with occupational exposure (0.9nM), non-occupational exposure (0.8nM), and mixed exposure (0.8nM). Within asbestosis cases, those with higher profusion scores had higher SMRP values than those with lower profusion scores (1.6 vs. 0.8nM). Based on multi-regression analysis, the trend toward elevation of SMRP remained significant in subjects with occupational exposure or in those with asbestosis, as compared with healthy subjects without exposure (p<0.01), although body mass index had an effect on SMRP (p<0.0001). Regardless of the differences in SMRP levels among these subgroups, MSLN methylation ranged from 80.5 to 92.5%, with no significant difference. The elevated level of SMRP in asbestosis with higher profusion scores could not be attributed to low MSLN methylation status. Our findings suggest that the elevation of SMRP is related to asbestos exposure and benign ARDs especially for cases with high profusion scores, which is independent of MSLN methylation.

Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic.

Pleural mesothelioma is a highly aggressive and difficult-to-treat form of cancer induced by asbestos in 80-90% of cases. The population group most at risk of the condition are asbestos-exposed workers. Mesothelin or soluble mesothelin-related protein (SMRP) is studied as a potential marker of mesothelioma in the at-risk population. The study comprised 239 subjects with a mean duration of occupational exposure to asbestos of 19.9 years. In all of them, a complete medical history was taken, focused on exposure duration and a physical examination, a chest X-ray or other imaging investigations and a lung function test were performed. Their serum SMRP levels were measured and biopsy samples were taken to diagnose pleural disease. Based on the above examinations, the subjects were classified into subgroups and serum SMRP concentrations were statistically analyzed with respect to individual parameters. In asbestos-exposed individuals, mesothelin levels were significantly higher in those with pathological X-ray findings than in those with normal X-ray results (0.78 ± 0.63 vs. 0.50 ± 0.35, P<0.0001). The group of patients with benign disease had statistically significantly higher mesothelin levels than those with normal X-ray findings (0.755 ± 0.543 vs. 0.50 ± 0.35, P<0.001). In the group with present malignant processes, mesothelin levels were higher than in individuals with benign disease (1.19 ± 0.89 vs. 0.76 ± 0.54, P=0.015). Only a weak correlation was found between mesothelin levels and asbestos exposure duration. There were relatively high sensitivity and high specificity (75% and 90.6%, respectively) of serum mesothelin for pleural mesothelioma. However, given the small number of mesothelioma cases in the group, the results cannot be considered as statistically significant. In persons followed up for asbestos exposure, increased mesothelin levels signalize pathological processes in the chest and correlate with severity of the disease. The study suggests that mesothelin cannot be considered a reliable marker for the early stage of malignant degeneration of pleural disease but only an additional criterion for examination of the followed-up individuals.

Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA ( p = 0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects ( p = 0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.

Bronchoalveolar lavage fluid cellular profile in workers exposed to chrysotile asbestos

The cellular profile of bronchoalveolar lavage fluid (BALF) in asbestos-exposed population remains controversial. We, therefore, aimed to investigate BALF in apparently healthy individuals that were exposed in asbestos-related work for a long period of time. Participants were selected among employees of a car brakes and clutches factory that used chrysotile asbestos. Selection criteria were an employment history of ≥ 15 years and the absence of severe respiratory disease. The total number and type of BALF cells, the existence of dust cells, iron-laden macrophages and asbestos bodies were assessed. Thirty-nine workers (25 men), with a mean age of 46.2 ± 4.2 years and a mean employment time of 23.5 ± 4 years, participated. Asbestos bodies were observed in 14 out of 39 (36%) specimens, dust cells in 37 and iron-laden macrophages in all. Those with asbestos bodies had at least 3 times higher probability to have lymphocytosis (lymphocytes > 11%: 64% vs 28%, p = 0.027) and had an increased percentage of iron-laden macrophages compared to those without asbestos bodies (median values: 42% vs 13%, p = 0.08). Smokers (36%) had less lymphocytes compared to non and ex-smokers (median values: 6% vs. 13%, p = 0.002), and iron-laden macrophages count had a positive relation (r = 0.31, p = 0.05) to lymphocyte count. Asbestos-exposed asymptomatic individuals with the presence of asbestos bodies in the BALF are more likely to have lymphocytic alveolitis while concurrent dust exposure and smoking habits hold a significant role.

Mesothelin and kidney function—Analysis of relationship and implications for mesothelioma screening

PurposeMalignant mesothelioma (MM) carries a poor prognosis and remains a major public health issue in many countries. Outcomes may be improved with earlier detection and this justifies screening the at-risk asbestos-exposed population. Soluble mesothelin is a potential biomarker for MM, but it has been observed to be elevated in patients with reduced kidney function. Defining the relationship between mesothelin concentrations and kidney function will allow more accurate interpretation of this assay. Materials and methodsA cross-sectional study consisting of 144 patients with chronic kidney disease (CKD) was conducted at Sir Charles Gairdner Hospital and Royal Perth Hospital in Western Australia. Only patients with CKD stages II–V were recruited while those with a history of renal transplant, dialysis, or malignancy were excluded. Serum and urine mesothelin and creatinine concentrations were determined. ResultsThere were 33, 49, 31 and 31 patients in CKD stages II, III, IV and V, respectively recruited. Serum mesothelin increased significantly with increasing serum creatinine (p<0.0001), and worsening stage of CKD (p<0.0001). A significant correlation between urine mesothelin to creatinine ratio and serum mesothelin concentration was detected (p=0.002). No significant difference was found in urine mesothelin to creatinine ratios across the four CKD stage groups. ConclusionSerum mesothelin concentration is elevated in individuals with renal impairment. Renal function should therefore be taken into account during interpretation of this assay.

Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population

Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study. Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations. The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001). This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.

Osteopontin Levels in an Asbestos-Exposed Population

Serum osteopontin levels in patients with malignant mesothelioma have been reported to be higher than in healthy subjects. This study assessed serum osteopontin levels in an asbestos-exposed population to test whether nonmalignant asbestos-related disorders could influence osteopontin levels. This cross-sectional study evaluated serum osteopontin levels in 525 male subjects. Subjects were classified into six different diagnostic groups, including asbestosis (n=23), silicosis (n=20), diffuse pleural thickening (n=110), asbestosis and diffuse pleural thickening (n=13), pleural plaques (n=142), and healthy subjects with a history of asbestos exposure (n=217). Mean serum osteopontin levels differed among the six groups (P<0.0001). Mean osteopontin values of the healthy individuals exposed to asbestos were significantly different from that of subjects with asbestosis (P<0.001) and diffuse pleural thickening (P<0.001). There was a significant difference in mean serum levels of osteopontin in healthy individuals exposed to asbestos (n=217) compared with the group mean of all subjects with asbestos-related disorders (n=288; P<0.0001). Our results suggest that osteopontin levels are elevated in subjects with asbestos-related disorders without malignant mesothelioma. These data indicate that osteopontin, although reported to be useful for detecting malignant mesothelioma in asbestos-exposed individuals, may be influenced by nonmalignant processes.

Soluble Mesothelin-related Protein in an Asbestos-exposed Population

Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown. We aimed to evaluate SMRP in an asbestos-exposed cohort. A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography. Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01). This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Low-Dose Computed Tomography Screening for Lung Cancer and Pleural Mesothelioma in an Asbestos-Exposed Population: Baseline Results of a Prospective, Nonrandomized Feasibility Trial—An Alpe-Adria Thoracic Oncology Multidisciplinary Group Study (ATOM 002)

To evaluate the feasibility of using low-dose computed tomography (LDCT) for the early diagnosis of lung cancer and malignant pleural mesothelioma in an asbestos-exposed population. Between February 2002 and October 2003, 1,045 volunteers already enrolled in a surveillance program for asbestos-exposed workers and former workers were recruited. The main eligibility criteria were: written informed consent, definite exposure to asbestos, age 40-75, no prior cancer or severe concomitant conditions, no chest CT scan in the past 2 years. A smoking history was not required. After a structured interview, chest X-ray (CXR) and LDCT were performed. Participants with negative examinations were assigned to annual LDCT. Participants with positive findings received high-resolution CT and additional diagnostic workup as appropriate. Baseline characteristics of the screened population were: median asbestos exposure time, 30 years; median age, 58; median pack-years in smokers/former smokers, 18.5. Thirty-four percent had never smoked. On LDCT, 834 noncalcified nodules were identified in 44% of participants, versus 43 nodules in 4% on CXR. Pleural abnormalities were observed in 44% and 70% of participants by CXR and LDCT, respectively. Overall, LDCT identified nine cases of non-small cell lung cancer-eight stage I, one stage IIA-and one thymic carcinoid, corresponding to 1% of the enrolled population. All cases were radically treated. None had been detected by CXR. No pleural mesothelioma was diagnosed. There were 11 false-positive results. Our findings first suggest that LDCT may be at least as useful in asbestos workers as in heavy smokers for the early diagnosis of lung cancer; this benefit is evident even in a poor-risk population, with low rates of smoking prevalence and a previous history of radiological surveillance. The role of spiral tomography in screening for pleural mesothelioma remains uncertain.