Unit of Medical Statistics and Cancer Epidemiology, CPO Piemonte and University of Eastern Piedmont, Novara, Italy. daniela.ferrante@med.unipmn.it

BACKGROUND: Family members of asbestos workers are at increased risk of malignant mesothelioma (MM). Although the hazard is established, the magnitude of the risk is uncertain, and it is unclear whether risk is also increased for other cancers. Few cohort studies have been reported. OBJECTIVE: The “Eternit” factory of Casale Monferrato (Italy), active from 1907 to 1986, was among the most important Italian plants producing asbestos-cement (AC) goods. In this article we present updated results on mortality and MM incidence in the wives of workers at the factory. METHODS: We studied a cohort of 1,780 women, each married to an AC worker during his employment at the factory but not personally occupationally exposed to asbestos. Cohort membership was defined starting from the marital status of each worker, which was ascertained in 1988 from the Registrar’s Office in the town where workers lived. At the end of follow-up (April 2003), 67% of women were alive, 32.3% dead, and 0.7% lost to follow-up. Duration of exposure was computed from the husband’s period of employment. Latency was the interval from first exposure to the end of follow-up. RESULTS: The standardized mortality ratio (SMR) for pleural cancer [21 observed vs. 1.2 expected; SMR = 18.00; 95% confidence interval (CI), 11.14-27.52] was significantly increased. Mortality for lung cancer was not increased (12 observed vs. 10.3 expected; SMR = 1.17; 95% CI, 0.60-2.04). Eleven incident cases of pleural MM were observed (standardized incidence ratio = 25.19; 95% CI, 12.57-45.07). CONCLUSIONS: Household exposure, as experienced by these AC workers’ wives, increases risk for pleural MM but not for lung cancer.

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Klinisch Arbeidsgeneeskundige, Academisch Medisch Centrum/Universiteit van Amsterdam, Coronel Instituut voor Arbeid en Gezondheid, Nederlands Centrum voor Beroepsziekten, Postbus 22.660, 1100 DD Amsterdam. g.vanderlaan@amc.uva.nl

Whereas the carcinogenic properties of asbestos have been known for more than 70 years, the mesothelioma epidemic in Europe has not yet reached its peak. After occupationally induced cases, environmental cases are being revealed at an ever-increasing rate. In 2005 a total ban on the production and use of asbestos in Europe was announced. Worldwide, the use of asbestos has shifted towards emerging economies such as those occurring in Asia. Economic reasons and a strong lobby from the asbestos industry explain the delay in the implementation of proper preventive actions as well as the global shift. The WHO and the International Labour Office are collaborating towards the elimination of asbestos-related diseases worldwide. More awareness is needed in order to prevent similar tragedies occurring from other side effects of work.

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Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, via Tronto 10/A, Torrette di Ancona, Ancona, Italy.

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2′-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

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 The Friarage Hospital Northallerton, Northallerton, North Yorkshire DL6 1JG, UK. alexander.chapman@stees.nhs.uk

INTRODUCTION: Malignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK. METHOD: Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients’ hospital records and the Trust histology database were reviewed, as well as coroner’s reports on all patients with a post mortem diagnosis of mesothelioma. RESULTS: Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery/cutting CT biopsies or chest drains. 73/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92/146 (63%) had a performance status of 2 or better at diagnosis but only 54/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery. CONCLUSION: This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.

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 Centre for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Liburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.fennell@qub.qc.uk

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

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