Malignant pleural mesothelioma: an update on biomarkers and treatment

Our plain-English summary of Malignant pleural mesothelioma: an update on biomarkers and treatment, by M. Ray, H.L. Kindler (Chest, 2009).

The study

• Authors: M. Ray, H.L. Kindler
• Journal: Chest
• Published: 2009;136(3):888-896
• Type of article: Review
• Cited by: 108 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.

In plain English

This article was a narrative review, not an original study. The authors summarized published research on malignant pleural mesothelioma, covering its causes, diagnosis, staging, blood biomarkers and treatment. They described asbestos as the main cause and named radiation, genetics and possibly simian virus 40 as less common causes. No specific asbestos fiber types were discussed. In one cited study, three blood markers were measured in 66 mesothelioma patients and in comparison groups. At a specificity of 95%, the markers detected mesothelioma in 73% (soluble mesothelin-related peptide), 47% (osteopontin) and 34% (megakaryocyte potentiation factor) of cases. A prospective study of 538 asbestos-exposed people found no mesotheliomas and reported a high false-positive rate. An analysis of 663 surgical patients found no statistical difference in survival between the two main operations. In a 456-patient trial, median survival was 12.1 months with pemetrexed plus cisplatin and 9.3 months with cisplatin alone. The authors noted that several biomarker studies were small and retrospective and that larger prospective studies were needed. They concluded that targeted drugs may become treatment options as the disease is better understood.

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 research on malignant pleural mesothelioma (no original data)
• Who was studied: No study population of its own. The review covered published studies of patients with malignant pleural mesothelioma and of asbestos-exposed people, mainly in the United States and Europe.
• Exposure: Asbestos in general (no specific fiber types named) as the main cause. Therapeutic radiation, genetic predisposition (including in people exposed to erionite in Cappadocia, Turkey) and possibly simian virus 40 were discussed as less common causes.
• Main results:
  • In a cited study of 66 patients with mesothelioma, 20 healthy control subjects and 81 others, at a specificity of 95%, sensitivity for detecting mesothelioma was 34% for megakaryocyte potentiation factor, 47% for osteopontin and 73% for soluble mesothelin-related peptide. Combining the three markers did not improve sensitivity.
  • In a cited earlier study, serum soluble mesothelin-related peptide was elevated in 84% of patients with mesothelioma, compared with 2% of patients with other cancers or lung diseases.
  • The first cited prospective study of soluble mesothelin-related peptide in asbestos-exposed individuals reported a high false-positive rate. No mesotheliomas were detected among the 538 subjects tested.
  • A cited analysis of 663 consecutive patients treated with extrapleural pneumonectomy or pleurectomy/decortication found no statistical difference in survival by procedure at any stage. The 5-year overall survival rate was 12%.
  • In a cited phase III trial of 456 patients, pemetrexed plus cisplatin gave a higher response rate than cisplatin alone (41% vs 17%), longer survival (12.1 vs 9.3 months) and a longer time to progression (5.7 vs 3.9 months).
  • In the cited British MS01 trial of 409 patients, survival with chemotherapy compared with active symptom control alone (8.5 vs 7.6 months) was not statistically significantly different.
• The authors' conclusion: The authors concluded that, as more is learned about mesothelioma biology, molecularly targeted agents may become treatment options.
• Limitations the authors state:
  • The authors stated that several of the series evaluating the three new biomarkers were small and retrospective, and that larger prospective studies will be required to fully validate them.
  • The authors stated that no staging system adequately predicts prognosis in patients who have not had surgery.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Asbestos Exposure, Mesothelioma, Latency, Fluid Cytology, Staging, Prognosis.

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