The mesothelioma enigma

Our plain-English summary of The mesothelioma enigma, by R.M. Flores (The Journal of Thoracic and Cardiovascular Surgery, 2015).

The study

• Author: R.M. Flores
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2015;149(6):1548-9
• Type of article: Editorial, Comment
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this editorial commentary, the author discussed a study by Frischknecht and colleagues, published in the same issue. That study assessed whether ERCC1 and RRM1 levels, measured in pretreatment tissue biopsies, predicted outcome in patients with mesothelioma who underwent induction chemotherapy followed by extrapleural pneumonectomy (EPP). It found that high ERCC1 expression was associated with a worse prognosis and high RRM1 with a better one, and these findings were statistically significant by univariate analyses. The author noted that median survivals of 21 months for epithelioid and 12 months for mixed and sarcomatoid histology, reported for patients as far back as 1939, were similar to results today. He identified several weaknesses in the study. The multivariate model omitted histology, age, gender and nodal status. Freedom from recurrence was a suboptimal end point because radiologic assessment of mesothelioma is unreliable. The analysis also focused on patients who survived the treatment selection process, ignoring the intent-to-treat principle. He concluded that the prognostic role of the two markers was not clinically relevant at this time and that predictive ability had not been demonstrated. He also argued that induction chemotherapy followed by EPP is not standard treatment. He cited a meta-analysis in which median survivals after EPP and pleurectomy decortication were similar but operative mortality appeared 3-fold higher with EPP, and suggested reserving EPP as a last resort or eliminating it.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was an editorial commentary, not an original study. It discussed a study by Frischknecht and colleagues, published in the same journal. That study tested whether two tissue markers, ERCC1 and RRM1, measured in a biopsy before treatment, predicted outcome in patients who had induction chemotherapy followed by extrapleural pneumonectomy (EPP). As the author described it, that study found high ERCC1 was bad and high RRM1 was good for prognosis in a highly select group of patients. The author criticized the study for three things: it left histology, age, gender and nodal status out of its multivariate model; it used freedom from recurrence rather than overall survival as its end point; and it focused only on patients who got through the treatment selection process. The author concluded that the markers' prognostic role was not clinically relevant at this time. Citing a published meta-analysis, the author wrote that operative mortality appears 3-fold higher with EPP than with pleurectomy decortication. The author argued this favored reserving EPP as a last resort or eliminating it. Asbestos was not discussed.

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: editorial commentary on another study (no original data)
• Who was studied: No study population of its own. The commentary discussed a study by Frischknecht and colleagues of patients who underwent induction chemotherapy followed by extrapleural pneumonectomy (EPP).
• Exposure: Not an exposure study. Asbestos and fiber types are not discussed. The subject is prognostic markers (ERCC1 and RRM1) and surgical treatment of mesothelioma.
• Main results:
  • As described by the author, the Frischknecht study (not this article) found that high ERCC1 expression was bad and high RRM1 was good for prognosis in a highly select group of patients. These findings were statistically significant by univariate analyses.
  • The author criticized the Frischknecht study's multivariate model for leaving out histology. The author also noted that age, gender and nodal status were left out although they were statistically significant in univariate analyses.
  • The author called the commented study's primary end point, freedom from recurrence, suboptimal. The author noted that most mesothelioma studies use overall survival instead.
  • The author argued that the commented study looked only at patients who got through treatment selection. Patients who did not tolerate induction chemotherapy, patients who were unresectable at surgery, and operative deaths were left out.
  • Citing an earlier report (McCormack and colleagues), the author noted median survivals of 21 months for epithelioid and 12 months for mixed and sarcomatoid histology in patients from as far back as 1939. The author wrote that these were similar to results from today.
  • Citing a meta-analysis (Taioli, Wolf and Flores), the author wrote that median survivals after EPP and pleurectomy decortication are similar, but operative mortality appears 3-fold higher with EPP.
  • The author argued that this evidence favors reserving EPP as a procedure of last resort or eliminating it.
• The authors' conclusion: The author concluded that the prognostic role of ERCC1 and RRM1, although statistically significant in the commented study, is not clinically relevant at this time.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy, Extrapleural Pneumonectomy (EPP), Prognosis, Median Survival, Epithelioid, Sarcomatoid, Histology.

Related studies

• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)
• Discussion — (2015)
• Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival — Z.G. Zimling, J.B. Sørensen, et al. (2012)
• ERCC1, MLH1, MSH2, MSH6, and βIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural mesothelioma — S. Ting, F.D. Mairinger, et al. (2013)
• The issue of studies evaluating biomarkers which predict outcome after pemetrexed-based chemotherapy in malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients — T. Powrózek, D.M. Kowalski, et al. (2014)

Browse more research in The Journal of Thoracic and Cardiovascular Surgery, or return to medical research.