Update on malignant pleural mesothelioma

Our plain-English summary of Update on malignant pleural mesothelioma, by N.P. Campbell, H.L. Kindler (Seminars in Respiratory and Critical Care Medicine, 2011).

The study

• Authors: N.P. Campbell, H.L. Kindler
• Journal: Seminars in Respiratory and Critical Care Medicine
• Published: 2011;32(1):102-10
• Type of article: Review
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is an aggressive cancer principally attributable to asbestos. Although the incidence is now declining in the United States, it will continue to increase worldwide until all nations institute regulations limiting asbestos use and exposure. This is a heterogeneous disease, with three pathological subtypes that yield very different outcomes. Stage is less important than histology in determining prognosis. The biomarkers serum mesothelin-related peptide and osteopontin are being evaluated for screening asbestos-exposed individuals and monitoring disease response. The optimal surgical procedure remains controversial because extrapleural pneumonectomy and pleurectomy/decortication can achieve similar results. The reference chemotherapy regimen, pemetrexed-cisplatin, improves survival and quality of life. Key questions about maintenance therapy and the optimal regimens for elderly and frail patients remain to be answered. Although few other cytotoxic drugs have activity, a surprising number of novel agents are being investigated.

© Thieme Medical Publishers.

In plain English

This article was a review, not a new study. The authors summarized research on diagnosing and treating malignant pleural mesothelioma. They described the disease as principally attributable to asbestos and stated that at least 70% of patients have a definite history of asbestos exposure. Citing a database of 2680 patients, they reported median survival of 17 months with epithelial tumors and 6 months with sarcomatoid tumors. In a cited comparison of blood markers, with both tests set at a specificity of 95%, osteopontin had a sensitivity of 47% and soluble mesothelin-related peptide 73%. The only large screening study of the latter found a high false-positive rate and detected no mesotheliomas in over 500 high-risk people. A cited analysis of 663 surgical patients found no statistically significant survival differences between the two major operations at any stage. On multivariate analysis, however, survival significantly favored pleurectomy/decortication over extrapleural pneumonectomy. In a cited trial, pemetrexed plus cisplatin gave longer median survival than cisplatin alone (12.1 vs 9.3 months). The authors concluded that mesothelioma is almost entirely preventable if worldwide restrictions could be placed on asbestos use.

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 and ongoing clinical trials on malignant pleural mesothelioma (epidemiology, diagnosis, prognosis, staging, biomarkers, surgery, radiation, chemotherapy, novel agents)
• Who was studied: No new patients were studied; the review covered published research on patients with malignant pleural mesothelioma, drawn from many cited studies and trials
• Exposure: Asbestos in general (no specific fiber types named). The review stated that at least 70% of patients have a definite history of asbestos exposure. It also mentioned less common causes: therapeutic radiation, a genetic predisposition in Turkish families exposed to erionite, and possibly simian virus-40 (described as quite controversial). It said carbon nanotubes may have the potential to cause the disease, though this is far from proven.
• Main results:
  • Cited IASLC database of 2680 patients: median survival was 17 months for patients with epithelial histology and 6 months for patients with sarcomatoid tumors; biphasic cancers had an intermediate prognosis
  • Cited biomarker comparison at a specificity of 95%: osteopontin had a sensitivity of 47%, compared with 73% for soluble mesothelin-related peptide (SMRP)
  • Cited large prospective screening study of SMRP: a high false-positive rate was observed, and no mesotheliomas were detected in over 500 high-risk subjects
  • Cited analysis of 663 patients at three centers who underwent extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D): no statistically significant survival differences by procedure at any stage; operative mortality was 7% with EPP vs 4% with P/D
  • Same cited analysis of 663 patients: on multivariate analysis, the survival benefit favoring P/D over EPP remained significant (hazard ratio 1.4, p less than 0.001)
  • Cited phase III trial of 456 patients: those given pemetrexed plus cisplatin had a longer median overall survival than those given cisplatin alone (12.1 vs 9.3 months)
  • Cited British MS01 trial (409 patients): the small survival difference with chemotherapy over active supportive care was not statistically significant (8.5 vs 7.6 months)
  • Cited second-line phase III trial in 223 previously treated patients: pemetrexed improved progression-free survival over best supportive care (3.6 vs 1.5 months) but did not improve overall survival, which the authors attributed presumably to crossover
• The authors' conclusion: The authors concluded that mesothelioma is almost entirely preventable if worldwide restrictions could be placed on asbestos use. They also wrote that progress in diagnosis and management is modest but genuine, and that pemetrexed–cisplatin prolongs survival by a few months and enhances quality of life.
• Limitations the authors state:
  • The authors cautioned that a cited retrospective finding of longer survival with platinum–pemetrexed rechallenge could reflect selection bias inherent in a retrospective analysis
  • The authors noted that a cited gene expression ratio test for prognosis requires validation

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, Histology, Prognosis, Biomarker, Mesothelin, Osteopontin, Extrapleural Pneumonectomy (EPP), Pleurectomy/Decortication (P/D).

Related studies

• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Current status of screening for malignant pleural mesothelioma — H.I. Pass, M. Carbone (2009)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)

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