New blood test for lung cancer caused by asbestos

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24 October 2012

A lung cancer called mesothelioma caused over 2,000 deaths in the UK last year, more deaths than were caused by all road accidents. The number has been increasing steadily: it was only 153 in 1968. The cancer develops 20 to 50 years after breathing in airborne asbestos fibres in such jobs as insulating, boiler making, house building, ship building, plumbing and pipe fitting. Family members have been known to be exposed to asbestos via contaminated work clothes. Asbestos licensing regulations came into force in the UK in 1983.

Lung mesothelioma develops in a mesothelium membrane called pleura that covers the surface of the lung and folds back to line the inner part of the chest wall. Pleura normally secretes a little fluid between its two layers so that they can move easily over each other. Thickening by a mesothelioma makes breathing increasingly difficult, and breathlessness becomes worse if the tumour causes increased fluid secretion, forming a pleural effusion. Other symptoms are loss of appetite, chest pain, cough and difficulty sleeping. There is a similar membrane around the abdominal organs (peritoneum) that can more rarely develop a mesothelioma from swallowed asbestos fibres, causing abdominal pain, nausea and vomiting.

By the time symptoms appear and mesothelioma is diagnosed it has usually spread extensively. Treatment has shown little success: the average survival after diagnosis is only one year. Early detection is limited by the long period of development. Radiological screening of those exposed to asbestos has been unable to detect early stage disease. A laboratory test for plasma soluble mesothelin-related peptides (SMRP) shows raised values in mesothelioma that increase with tumour growth and decrease after surgical removal, chemotherapy or radiation treatment. However, patients with other cancers - including lung, ovarian, endometrial, and pancreatic cancers - can also have raised SMRP test results, so it cannot be used for screening.

A study published in the New England Journal of Medicine on 11 October 2012 reported that a protein called fibulin-3 is raised in the blood plasma and lung effusion fluid from patients with the disease. The researchers, led by Professor Harvey Pass of New York University Langone Medical Center, examined plasma and effusion samples from volunteers in Detroit and New York. There were 92 patients with mesothelioma and a total of 290 controls. Controls included healthy individuals, people exposed to asbestos in the past, patients with pleural effusions from benign causes or caused by breast and other cancers, and patients without effusions who had breast and other cancers.

Plasma fibulin-3 values in mesothelioma patients were four to five times higher than in controls. The values fell after surgical removal of tumour mass and rose again with recurrence. The researchers determined an optimal ‘cut-off’ value which 89 of the 92 values (96.7%) from mesothelioma patients exceeded. At this sensitivity of 96.7%, values below the cut-off were found in 277 of the 290 controls, showing the specificity of the test to be 95.5%.

Because plasma fibulin-3 may have the potential to become a screening test for early mesothelioma, a comparison was made between values in 28 patients with stage I or II disease and 136 volunteers who had been exposed to asbestos but had no mesothelioma. At a cut-off designed to include all the mesothelioma patients (sensitivity 100%), the specificity was 94.1%. The false positive rate (100 - specificity) of the test was 5.9%. (This figure is based on the whole group, of whom 17.0% had mesothelioma. Screening a population in which less than 17% had mesothelioma would give a false positive rate greater than 5.9%.)

Pleural fluid fibulin-3 values were found to average three times higher in effusions from patients with mesothelioma than from all other patients with effusions, whether or not due to malignant disease. Values of another lab test, vascular endothelial growth factor (VEGF), are also raised in mesothelioma effusions and have been used for monitoring. However, unlike SMRP, values are also raised in effusions not due to mesothelioma.

The authors of this study, which was supported by the Early Detection Research Network of the US National Institutes of Health and others, concluded that plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma, and that together with effusion fibulin-3 levels they can differentiate mesothelioma effusions from other benign and malignant effusions. They recommended an international effort to find out how soon plasma fibulin-3 is raised before the onset of symptoms, and to determine its value for monitoring patients following treatment.