New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

Our plain-English summary of New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma, by M. Rossini, P. Rizzo, I. Bononi, et al (Frontiers in Oncology, 2018).

The study

• Authors: M. Rossini, P. Rizzo, I. Bononi, A. Clementz, R. Ferrari, F. Martini, M.G. Tognon
• Journal: Frontiers in Oncology
• Published: 2018;8:91
• Type of article: Review
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.

In plain English

This article is a narrative review of published research on malignant pleural mesothelioma. It reported no new data and did not say how studies were chosen. Topics included asbestos, which the review said IARC has confirmed causes mesothelioma; erionite; inherited BAP1 mutations, described as a genetic predisposition; and simian virus 40, whose role it called debated. It also covered tumor gene changes, treatments and possible new tests. Among cited studies, a large study found surgery alone, compared with no treatment, associated with better survival (adjusted hazard ratio 0.64, 0.61 to 0.67). The MARS trial compared chemotherapy plus extra-pleural pneumonectomy and postoperative radiation with chemotherapy without the operation; median survival was 14.4 months and 19.5 months, respectively. The review described blood markers under study, including mesothelin, fibulin-3 and three circulating microRNAs, noting they still need validation in larger populations. It also discussed the Notch pathway, citing elevated Notch1 in mesothelioma cell lines. The authors concluded that genomic profiling, targeting pathways such as Notch, studying circulating microRNAs, and assessing asbestos exposure and germline BAP1 mutations should all be considered.

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 preclinical and clinical literature. No literature search method is described.
• Who was studied: No new participants. The review discusses previously published laboratory, animal and human studies of malignant pleural mesothelioma (MPM).
• Exposure: Background only. The review states that IARC confirmed all six regulated fibrous forms of asbestos (actinolite, amosite, anthophyllite, tremolite, crocidolite, chrysotile) are carcinogenic to humans, causing mesothelioma. It describes erionite as regarded the most potent carcinogenic mineral fiber and germline BAP1 mutations as a genetic predisposition. It says the possible roles of viral infection and radiation exposure are still debated. Its main focus is diagnosis and treatment.
• Main results:
  • The review cited a large study (stated in the text as 14,288 patients) in which surgery alone, compared with no treatment, was associated with improved survival (adjusted HR 0.64, 0.61 to 0.67). Radiation was not (adjusted HR 1.15, 1.08 to 1.23).
  • The review cited the MARS randomized trial. It compared patients assigned to extra-pleural pneumonectomy within trimodal therapy (chemotherapy, the operation, and postoperative hemithorax irradiation) with patients given chemotherapy but no pneumonectomy. Median survival was 14.4 months in the pneumonectomy group and 19.5 months in the no-pneumonectomy group.
  • The review cited earlier work showing that pemetrexed/cisplatin chemotherapy was more effective in MPM than cisplatin alone.
  • The review cited a trial in which tremelimumab (an immune checkpoint antibody) did not significantly prolong overall survival compared with placebo in previously treated MPM patients.
  • Cited studies reported soluble mesothelin sensitivity of 84% for advanced MPM and specificity of 95%.
  • A cited study by Pass et al. reported elevated plasma fibulin-3 in MPM patients, with specificity of 94% and sensitivity of 100%.
  • Circulating microRNAs miR-197-3p, miR-1281 and miR-32-3p, found in sera of MPM patients and workers formerly exposed to asbestos, have been proposed as non-invasive biomarkers.
  • Cited work found elevated Notch1 and reduced Notch2 in cell lines from human MPM biopsies.
• The authors' conclusion: The authors concluded that, to achieve early detection and longer survival with minimal side effects, four things should be considered: comprehensive genomic profiling of MPM; targeting pathways known to be dysregulated, such as Notch; characterizing dysregulated circulating microRNAs; and assessing risks such as asbestos exposure and germline BAP1 mutations.
• Limitations the authors state:
  • The authors noted that studies identifying circulating biomarkers of MPM still require definitive validation in larger populations.
  • The authors noted that, because Notch signaling is complex, it is not always possible to assess whether a given agent inhibits Notch.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Occupational Exposure, Environmental Exposure, Mesothelioma, Biomarker.

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