The evolution of multimodality therapy for malignant pleural mesothelioma

Our plain-English summary of The evolution of multimodality therapy for malignant pleural mesothelioma, by M.G. Zauderer, L.M. Krug (Current Treatment Options in Oncology, 2011).

The study

• Authors: M.G. Zauderer, L.M. Krug
• Journal: Current Treatment Options in Oncology
• Published: 2011;12(2):163-72
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm of the pleural surfaces that has been associated with asbestos exposure. MPM generally spreads locally along the ipsilateral pleura, especially at presentation, with distant metastatic disease typically seen only in the later stages of the disease course. As such, surgical resection and other local therapies have long been pursued as a primary form of treatment. Surgical options include debulking of the pleura by pleurectomy/decortication (P/D) or a more aggressive extrapleural pneumonectomy (EPP) which also involves removal of the lung, diaphragm, and involved pericardium. Even after major resection, MPM almost always recurs locally and has a poor prognosis. As such, many groups have pursued multimodality therapy, treating resectable patients with EPP, along with hemithoracic radiation to decrease the risk of local recurrence and chemotherapy to decrease the risk of distant metastatic disease. However, EPP is associated with significant morbidity and mortality, and many patients are not candidates for EPP due to underlying comorbid medical conditions. Additionally, many patients are unable to tolerate complete courses of adjuvant therapy after EPP. A large, multicenter retrospective analysis comparing EPP to P/D demonstrated better outcomes among those who underwent P/D. One challenge associated with P/D has been the delivery or radiation to the removed pleura with an intact lung. Yet, advances in radiation technique have allowed the exploration of high-dose radiation therapy after P/D. The ideal timing of chemotherapy relative to surgery and the role of intracavitary chemotherapy continue to be controversial issues. Clearly, MPM requires a multidisciplinary approach and, due to the myriad of open questions, much effort continues to focus on identifying the optimal combination of surgery, chemotherapy, and radiation.

In plain English

This article was a review and opinion piece, not a new study. It looked at published research on combining surgery, chemotherapy and radiation for malignant pleural mesothelioma, which the authors noted has been associated with asbestos exposure. They described two operations: extrapleural pneumonectomy (EPP), which removes the lung, and pleurectomy/decortication (P/D), which leaves the lung in place. Citing earlier studies, they reported that EPP carried morbidity of 22–37% and mortality of 4–15%. In 12 studies combining EPP, chemotherapy and radiation, median overall survival ranged from 14 to 28 months. In a cited retrospective analysis of 667 patients, those who had EPP had poorer survival than those who had P/D (hazard ratio 1.4). The authors noted that selection bias may have played a role. They also noted that no randomized trial had shown a benefit from any surgery. The authors concluded that chemotherapy before surgery, followed by P/D and pleural intensity modulated radiation therapy (IMRT), appeared promising but needed further study.

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: Review and opinion article summarizing published studies of multimodality treatment; no new patient data
• Who was studied: Published studies of patients with malignant pleural mesothelioma treated with surgery, chemotherapy and/or radiation (for example, 12 trimodality studies of EPP, chemotherapy and radiation reported over the preceding 6 years)
• Exposure: Not an exposure study. The article concerns treatments (EPP, P/D, chemotherapy, hemithoracic radiation, IMRT). It mentions only that the disease has been associated with asbestos exposure.
• Main results:
  • Citing earlier studies, EPP was associated with morbidity of 22–37% and mortality of 4–15%
  • Across the reviewed trimodality studies with EPP, about 80% of patients typically had a resection, and median overall survival ranged from 14 to 28 months
  • In a cited phase II trial giving 54 Gy of radiation to the chest cavity after EPP, the local recurrence rate was 13%
  • In a cited retrospective analysis of 667 patients, those who underwent EPP had poorer survival than those who had P/D, with a hazard ratio of 1.4 (no confidence interval given)
  • 6–16% of P/D patients were unable to complete adjuvant chemotherapy and radiation, compared with 19–61% of EPP patients
  • In the only prospective multimodality series using P/D, a small trial of 35 patients, median overall survival was 30 months
  • In the largest prospective trial of chemotherapy before EPP and radiation, median survival was 26 months for patients who responded to chemotherapy and 14 months for those with stable disease or progression
  • When IMRT was used after EPP, one series reported a 46% incidence of fatal pneumonitis
  • In a cited retrospective cohort of 36 patients treated with pleural IMRT, median survival for those who had P/D was 26 months, measured from the start of radiation; 20% of all patients had grade 3 or worse pneumonitis, and all but one recovered
  • No randomized trial had demonstrated a benefit of any surgery for malignant pleural mesothelioma
• The authors' conclusion: The authors concluded that the combination of neoadjuvant chemotherapy, P/D and adjuvant pleural IMRT appears to be a promising multimodality treatment approach, but that additional investigations are needed to refine it
• Limitations the authors state:
  • The EPP versus P/D comparison was retrospective, so selection bias may have played a role in the observed difference
  • Given the small number of patients with mesothelioma and the lack of randomized phase III trials, some questions may never be definitively answered

Topics

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

Medical terms in this study, explained in our Lexicon: Multimodal Therapy, Pleural Mesothelioma, Neoplasm, Asbestos Exposure, Ipsilateral pleura, Surgical Resection, Pleura, Pleurectomy/Decortication (P/D).

Related studies

• Role of integrated 18-fluorodeoxyglucose position emission tomography-computed tomography in patients surveillance after multimodality therapy of malignant pleural mesothelioma — C. Tan, S. Barrington, et al. (2010)
• Patterns of disease progression on 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients with malignant pleural mesothelioma undergoing multimodality therapy with pleurectomy/decortication — A. Bille, S. Chicklore, et al. (2013)
• Photodynamic therapy and the evolution of a lung-sparing surgical treatment for mesothelioma — J.S. Friedberg, R. Mick, et al. (2011)
• Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma — D.J. Sugarbaker, G.M. Strauss, et al. (1993)
• A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience — I. Opitz, M. Friess, et al. (2015)
• 18F-FDG PET/CT in the management of patients with malignant pleural mesothelioma being considered for multimodality therapy: experience of a tertiary referral center — H.S. Elliott, U. Metser, et al. (2018)

Browse more research in Current Treatment Options in Oncology, or return to medical research.