Cancer: better identified mesothelioma

This tumor, which mainly affects the pleura, is now much easier to spot, thanks to specialized analyses. Exposure to asbestos remains the main risk factor.

Mesothelioma is a cancer of the mesothelium. Very rare, it most often appears in the membrane formed of two layers which covers the lungs and the internal part of the chest wall called the pleura (it then takes the name of pleural mesothelioma). Affecting more men than women, it is generally the result of prolonged exposure to asbestos, but sets in slowly, with few specific symptoms for decades. Six out of 10 new cases are thus diagnosed in people over the age of 69.

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What signs?

The lungs are covered with a membrane made up of two layers. “One envelops the lung and the other lines the inside of the chest cavityexplains Dr Maurice Pérol, medical oncologist, specialist in thoracic tumors at the Léon-Bérard center in Lyon. Between these two layers which constitute the pleura (or mesothelium), circulates a small quantity of liquid which facilitates the movement of the lungs.But sometimes, following an infection or an inflammation, an abnormal volume of liquid accumulates between these two sheets and comes to compress the lungs: it is the pleural effusion. The person is short of breath, sometimes coughs, may suffer from chest pain. In addition to the clinical examination, various examinations will be prescribed to confirm this pleural effusion and identify its cause. It is generally on this occasion that the existence of mesothelioma is discovered.

What causes?

The main recognized risk factor for pleural mesothelioma is asbestos, which is classified as a “certain carcinogen” by the International Agency for Research on Cancer (IARC). Used before 1997 in construction as an insulating and fireproofing substance, this fiber is thus implicated in 80% of lung cancers recognized as occupational diseases and in 83% of mesotheliomas, over the period 2013-2017 (1). It was this abnormally high number of mesotheliomas in people exposed to asbestos in their professional activity that sounded the alarm and led to its use being banned in 1997. However, this fiber is still present in buildings constructed before that date and, above all, the complications of exposure to asbestos can appear up to 40 years later.

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These people have inhaled asbestos fibers which reach and attack the cells of the pleura (direct breaks in their chromosomes). A significant inflammatory and fibrotic reaction follows, as well as the production of a greater quantity of pleural fluid. “This very prolonged phenomenon of inflammation generates the production of free radicals: they also alter the chromosomes of the mesothelial cells (DNA damage), which leads to the presence of mutations, then the transformation of the cells of the pleura into cancerous cells.says Professor Françoise Galateau-Sallé, pathologist in the anatomopathology department specializing in thoracic oncology at the Léon-Bérard Center, a national expert center for the management of cancers of the pleura. Genetic analysis of tumors has thus made it possible to highlight alterations in tumor suppressor genes, characterizing mesothelioma.»

In about 5% of people with mesothelioma, we found “constitutional genetic abnormalities in the face of asbestos, which predispose to the development of mesothelioma, but also to other cancers (kidney, uveal and cutaneous melanoma, etc.) (2)“, continues Professor Galateau-Sallé (3).

More rarely, some pleural mesotheliomas occur about 10 years after radiotherapy prescribed to fight cancer (Hodgkin’s disease, breast cancer, etc.) (4).

What shapes?

Mesothelioma is a tumor that can take various forms during its development, which sometimes makes its diagnosis complex. One of the main difficulties is to differentiate a primary cancer of the pleura from metastases which develop there but come from another bronchopulmonary or breast cancer. Several markers make it possible to identify mesothelial cells with good specificity. According to the histological analysis of the tumour, a distinction is made between epithelioid mesotheliomas (80% of cases), sarcomatoids (the most severe forms) and mixed forms, each with a different prognosis. The diagnosis is then confirmed by a group of expert pathologists (Mesopath college). Depending on the results of the analyses, the tumor is classified according to its stage and its degree of aggressiveness (high or low).

What treatments?

After a multidisciplinary consultation meeting, the doctors submit the most appropriate treatment to the patient. “Most often, the disease is very diffuse, therefore inoperable“, underlines Dr. Pérol. In rare cases, however, at the onset of the disease, total removal of the pleura (pleurectomy) may be proposed. For all other cases, doctors have molecules that help slow the progression of the disease, in particular the progressive thickening of the pleura that compresses the lungs, and relieve symptoms.

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Until last year, first-line treatment combined chemotherapy and antiangiogenics, drugs that block the abnormal development of blood vessels within the tumour. Currently, oncologists rather favor the combination of two immunotherapy molecules. Administered intravenously, as a cure every 3 weeks, they help the immune system to fight mesothelioma cells. “The results are not as spectacular as for melanoma or lung canceradmits Dr Pérol, but they are better than with chemotherapy alone, especially in the most aggressive sarcomatoid forms. Patients generally benefit successively from the two types of treatment. Today, we have reached approximately 18 months of survival.»

Ongoing clinical trials relate to a type of immunotherapy (CAR-T cells) but this tumor remains incurable in almost all cases, even if certain forms progress very slowly.

(1) Occupational risk health insurance.

(2) Cancer Discov. 2020 Aug; 10 (8): 1103-1120.

(3) Cancer Treat Rev. 2020 Nov; 90:102091.

(4) Arch Pathol Lab Med. 2018 Jun; 142 (6): 753-760.

(5) PNSM, Public Health France.

A predominantly occupational disease

In 2016, half of people with pleural mesothelioma had worked in the construction sector, a figure that has been constantly increasing since 1998. And for 97% of them, we found, in a probable or very probable way, a occupational exposure to asbestos. Pleural mesothelioma therefore appears in tables of occupational diseases no. 30 (general scheme) and no. 47 (agricultural scheme) generated by exposure to asbestos.

To obtain this recognition as an occupational disease, proof of exposure is not necessary, the diagnosis of mesothelioma, certified by a group of experts, is sufficient. In this case, in addition to the allowances paid by Social Security, the person benefits from 100% coverage of medical care related to his occupational disease (based on and within the limits of Health Insurance rates) and it can file a claim for compensation with the Asbestos Victims Compensation Fund (Fiva) for damages. When the person is deceased, his heirs can benefit from it.

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However, between 2005 and 2017, only a quarter of people with mesothelioma and affiliated to the general social security system had undertaken a process of recognition of occupational disease, and had applied for Fiva (5). No doubt because the procedures are long and complex, but “do not hesitate to get help from a patient association or a service dedicated to occupational diseasesinsists Dr Pérol.


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