Induction Therapy for Mesothelioma

Our plain-English summary of Induction Therapy for Mesothelioma, by I. Opitz, W. Weder (Seminars in Thoracic and Cardiovascular Surgery, 2015).

The study

• Authors: I. Opitz, W. Weder
• Journal: Seminars in Thoracic and Cardiovascular Surgery
• Published: 2015;27(2):240-9
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

One particular approach of multimodality treatment for mesothelioma is induction therapy followed by surgery. Among its several advantages, the most important is downstaging of the tumor into a resectable stage, although morbidity and mortality might be increased. In this article we review the principles and outcome of different modalities for induction treatment of mesothelioma.

Copyright © 2015 Elsevier Inc. All rights reserved.

In plain English

This article is a review of induction therapy, meaning treatment given before surgery, for malignant pleural mesothelioma. The two authors work in the Division of Thoracic Surgery at the University Hospital Zurich. The article does not study asbestos exposure. The authors reviewed published studies of chemotherapy before extrapleural pneumonectomy (EPP) or pleurectomy and decortication (P/D). Their tables include only studies with at least 50 patients. They also described induction radiotherapy and targeted drugs. In their own experience of 142 EPP operations after 3 cycles of cisplatin with gemcitabine or pemetrexed, they observed no complete response. They reported published response rates of 30%-40% and noted that the only available response measure lacks reproducibility. Reported median survival after induction chemotherapy followed by EPP or P/D ranged from 10.2 to 59 months. In a Toronto radiotherapy-first protocol cited by the authors, 3-year survival among 25 patients was 84% for epithelioid and 13% for biphasic subtypes. The authors concluded that induction chemotherapy before surgery is feasible and can lead to improved outcomes with acceptable mortality and morbidity. They added that patient selection is hampered by a lack of markers that predict response to chemotherapy.

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 induction therapy followed by surgery for mesothelioma, with some reference to the authors' own institutional experience
• Who was studied: published studies of patients with malignant pleural mesothelioma treated with induction therapy before surgery; the summary tables consider only studies with 50 or more patients
• Exposure: No asbestos exposure is studied. The exposures reviewed are treatments: induction chemotherapy (for example cisplatin with gemcitabine or pemetrexed) before EPP or P/D, induction radiotherapy, and targeted drugs (dasatinib, VS-6063/defactinib).
• Main results:
  • In the authors' own experience of 142 EPP operations after 3 cycles of cisplatin with gemcitabine or cisplatin with pemetrexed, no complete response was observed. One patient had a nearly complete response after 3 cycles of cisplatin with pemetrexed.
  • Response rates to induction chemotherapy reported in the literature were 30%-40%. The authors note that reliable response assessment is lacking.
  • Patients whose disease progressed during induction chemotherapy had a significantly worse prognosis. This comes from the authors' own data, described as accepted for publication.
  • According to the cited literature, mortality after EPP in experienced centers can be reduced to 2%-5%, while morbidity remains high at 22%-82%.
  • A cited review by Cao et al found lower mortality after extended pleurectomy and decortication than after EPP (2.9% vs 6.8%). Morbidity was also lower after the lung-sparing procedure (27.9% vs 62% for EPP).
  • In the studies reviewed, median survival after induction chemotherapy followed by EPP or P/D ranged from 10.2 to 59 months. The authors describe this as comparable to adjuvant chemotherapy after surgery, where median survival was 13-24 months.
  • In the cited Toronto SMART protocol, 25 patients received high-dose intensity-modulated radiotherapy followed by EPP. Three-year survival was 84% for epithelioid and 13% for biphasic subtypes, and 1 patient died of treatment-related toxicity.
  • Preliminary data from an ongoing trial showed stable disease in 12 of 14 patients after 4 weeks of dasatinib given before surgery.
  • Across the literature reviewed, the authors judged that surgical mortality and morbidity seem not to be increased after induction chemotherapy.
• The authors' conclusion: The authors concluded that induction chemotherapy before surgery for malignant pleural mesothelioma is feasible and can lead to improved outcomes with acceptable, generally manageable mortality and morbidity. They added that patient selection is hampered by a lack of markers that predict response to chemotherapy, and that radiotherapy or targeted therapy as induction warrant further investigation.
• Limitations the authors state:
  • Response assessment in mesothelioma is unreliable; the only available tool, modified RECIST criteria, lacks reproducibility.
  • No validated biological marker is available to help select patients for induction chemotherapy.
  • Morbidity data are hard to compare across studies because reporting and definitions are very heterogeneous.

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.

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)
• Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma — E.H. Baldini, W.G. Richards, et al. (2015)
• 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)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)
• Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? — P. Mordant, K. McRae, et al. (2016)

Browse more research in Seminars in Thoracic and Cardiovascular Surgery, or return to medical research.