Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Our plain-English summary of Mesothelioma: Scientific clues for prevention, diagnosis, and therapy, by M. Carbone, P.S. Adusumilli, H.R. Alexander, et al (CA: A Cancer Journal for Clinicians, 2019).

The study

• Authors: M. Carbone, P.S. Adusumilli, H.R. Alexander, P. Baas, F. Bardelli, A. Bononi, R. Bueno, E. Felley-Bosco, F. Galateau-Salle, D. Jablons, A.S. Mansfield, M. Minaai, M. de Perrot, P. Pesavento, V. Rusch, D.T. Severson, E. Taioli, A. Tsao, G. Woodard, H. Yang, M.G. Zauderer, H.I. Pass
• Journal: CA: A Cancer Journal for Clinicians
• Published: 2019;69(5):402-429
• Type of article: Review
• Cited by: 390 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

© 2019 American Cancer Society.

In plain English

This article was a narrative review by a group of mesothelioma researchers and clinicians of published evidence on the causes, diagnosis and treatment of mesothelioma. It did not collect new data. The authors described the six regulated asbestos fibers: the amphiboles crocidolite, actinolite, tremolite, anthophyllite and amosite, and the serpentine chrysotile. They also discussed other mineral fibers such as erionite. Citing US data, they reported that the age-adjusted incidence rate fell from 2.5 cases per 100,000 persons at its peak to 0.88 in 2015, while deaths stayed at approximately 3000 per year. They cited a meta-analysis of non-occupational exposure that reported odds ratios for pleural mesothelioma of 5.4 (95% CI 2.6 to 11.2) for household exposure and 6.9 (95% CI 4.2 to 11.4) for neighborhood exposure. They also cited a French study in which expert pathologists changed 14% of 5258 diagnoses. They reported that germline mutations, mainly of BAP1, were found in approximately 12% of patients. In one large series, only 8% of patients with peritoneal mesothelioma reported asbestos exposure. The authors concluded that misdiagnosis should be reduced and that patients should be genotyped.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies, registry data and clinical trials on mesothelioma epidemiology, causes, genetics, diagnosis, staging, prognosis and treatment; no new data were collected
• Who was studied: No study population of its own; the review drew on published studies and registry data on mesothelioma patients, mainly from the United States, Europe and Australia, with some data from Latin America, Asia and other regions
• Exposure: Occupational and non-occupational asbestos exposure (amphiboles crocidolite, actinolite, tremolite, anthophyllite and amosite; serpentine chrysotile), other environmental mineral fibers such as erionite, talc, SV40, therapeutic radiation, and inherited germline mutations such as BAP1
• Main results:
  • Cited US registry data: the age-adjusted mesothelioma incidence rate peaked at 2.5 cases per 100,000 persons in the 1980s and early 1990s
  • Cited US data: the age-adjusted incidence rate fell further to 0.88 cases per 100,000 persons in 2015
  • Cited US data: the number of deaths per year in the United States stayed stable at approximately 3000
  • Cited meta-analysis of 18 studies (665 cases) of non-occupational exposure and pleural mesothelioma: odds ratio 5.4 (95% CI 2.6 to 11.2) for household exposure and 6.9 (95% CI 4.2 to 11.4) for neighborhood exposure, with the strongest associations when amphibole was present and the weakest when chrysotile was present
  • Cited French study of 5258 mesotheliomas: an expert pathology panel changed 14% of diagnoses to other conditions
  • Pathogenic germline mutations, of BAP1 and less often of other tumor suppressor genes, were reported in approximately 12% of patients with mesothelioma
  • Peritoneal mesothelioma was described as rarely associated with asbestos exposure; in one large series only 8% of patients reported exposure
  • On talc, the authors stated that the hypothesis that talc products caused mesothelioma was largely based on case reports, and that they were not aware of supporting epidemiological, mechanistic or animal evidence
  • Cited MARS randomized trial: worse survival among patients who underwent extrapleural pneumonectomy than among similar early-stage patients managed with chemotherapy alone
• The authors' conclusion: The authors concluded that, while awaiting trial results, patients could be helped by reducing misdiagnosis (estimated at 14% in France and up to 50% in some developing countries) and by genotyping patients to identify carriers of germline mutations
• Limitations the authors state:
  • The authors noted that data from developing countries give minimal information about methodology and accuracy of diagnosis
  • The authors noted that about 20% to 25% of mesotheliomas are not coded correctly and so are missed by statistics
  • The authors noted that exposure histories are less reliable for individuals than for cohorts

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Incidence, Carcinogenic, Discovery, BAP1, BAP1 Tumor Predisposition Syndrome, Pleural Mesothelioma, Peritoneal Mesothelioma.

Related studies

• Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations — M. Carbone, H.I. Pass, et al. (2022)
• BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos — F. Novelli, A. Bononi, et al. (2021)
• Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2020)
• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy — P. Star, A. Goodwin, et al. (2018)
• Integrative Molecular Characterization of Malignant Pleural Mesothelioma — J. Hmeljak, F. Sanchez-Vega, et al. (2018)

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