Novel induction therapies for pleural mesothelioma

Our plain-English summary of Novel induction therapies for pleural mesothelioma, by L. Donahoe, J. Cho, M. de Perrot (Seminars in Thoracic and Cardiovascular Surgery, 2014).

The study

• Authors: L. Donahoe, J. Cho, M. de Perrot
• Journal: Seminars in Thoracic and Cardiovascular Surgery
• Published: 2014;26(3):192-200
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is becoming increasingly common, and rates of diagnosis are expected to continue to increase in the coming years because of the extensive use of asbestos in industrialized countries and the long time interval between exposure and onset of disease. Although much research has been done on the optimal treatment for this disease, the overall prognosis remains grim. The main components of therapy are surgery, chemotherapy, and radiation therapy, but there is controversy in the literature about the optimal inclusion and sequencing of these treatments, as each has unique risk profiles. We have developed a new Surgery for Mesothelioma After Radiation Therapy protocol consisting of induction-accelerated hemithoracic radiation followed by extrapleural pneumonectomy. The rationale behind this protocol is to maximize both the tumoricidal and immunogenic potential of the radiotherapy while minimizing the radiation toxicity to the ipsilateral lung. Our initial trial demonstrated the feasibility of this approach and has shown encouraging results in patients with epithelial histology. In this article, we reviewed the current literature on induction chemotherapy for mesothelioma as well as described the Surgery for Mesothelioma After Radiation Therapy protocol and upcoming studies of novel induction therapies for mesothelioma.

Copyright © 2014 Elsevier Inc. All rights reserved.

In plain English

This was a review article from the Toronto Mesothelioma Research Program. The authors reviewed published studies that gave chemotherapy before extrapleural pneumonectomy (removal of the lung, chest lining and nearby tissues) followed by radiation for pleural mesothelioma. Across those studies, median survival for all patients ranged from 13 to 26 months. The authors also described their own protocol, called SMART: one week of radiation to one side of the chest (25 Gy in 5 daily doses, plus a 5 Gy boost to high-risk areas), then extrapleural pneumonectomy within two weeks. Chemotherapy followed only for patients whose lymph node disease was classed as ypN2. Of the first 50 SMART patients, 1 (2%) died from treatment. After surgery, 58% had ypN2 disease. After a median follow-up of 23 months, survival was significantly better for patients with epithelial tumors than for those with biphasic tumors. For epithelial tumors, 3-year survival was 72%, compared with 32% in the authors' earlier group treated with chemotherapy first. The authors concluded that SMART has shown promising results in patients with epithelial histology. The article did not study asbestos exposure.

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 article (published in the journal's News and Views section) of induction treatments for pleural mesothelioma, including a description of the authors' own SMART protocol and its early results
• Who was studied: Published trials of induction chemotherapy, extrapleural pneumonectomy and radiation, summarized in a table. Also the first 50 patients treated with SMART at the authors' Toronto institution (41 men, 9 women; 35 epithelial and 15 biphasic tumors), with an ongoing phase II trial planned for 100 patients.
• Exposure: Treatments, not asbestos exposure, were the subject. SMART consisted of 25 Gy of radiation in 5 daily fractions over 1 week to the whole affected side of the chest, plus a 5 Gy boost to high-risk areas. Extrapleural pneumonectomy followed within 2 weeks. Chemotherapy with cisplatin and pemetrexed or raltitrexed was given afterward only to patients with ypN2 disease. Asbestos was mentioned only as the reason diagnoses are expected to increase.
• Main results:
  • In the reviewed studies of chemotherapy before surgery and radiation, median survival was 29-59 months for patients who completed all three treatments. It was 9-14 months for patients who could not complete them.
  • Among the first 50 SMART patients, 1 patient (2%) died from treatment (an empyema after discharge).
  • Serious (grade 3 or higher) complications occurred in 52% of patients in the initial experience. The authors reported this is currently approximately 10% in patients with epithelial disease undergoing SMART.
  • In the initial cohort, partial wound dehiscence occurred in 4 of 25 patients (16%). The authors reported that changes to the surgical technique resolved this.
  • On final pathology, 96% of SMART patients had ypT3 or ypT4 tumors and 58% had ypN2 disease.
  • After a median follow-up of 23 months, median survival was significantly better for epithelial than for biphasic tumors in the SMART patients.
  • For biphasic tumors, survival was very similar between SMART and the authors' historical trimodality cohort (median survival 10-12 months). For epithelial tumors, 3-year survival was 72% with SMART compared with 32% in the historical trimodality cohort.
• The authors' conclusion: The authors concluded that the ideal treatment for mesothelioma is still unknown. They reported that the SMART approach, radiation before extrapleural pneumonectomy, has shown promising results in patients with epithelial histology. They said future directions include targeted and immunologic therapies.
• Limitations the authors state:
  • The authors stated that clinical staging of pleural mesothelioma remains a major limitation for grouping patients in trials. In this series, 58% had N2 disease on final pathology even though CT and PET scans had shown no evidence of mediastinal lymph node involvement.

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: Pleural Mesothelioma, Malignant Mesothelioma, Prognosis, Chemotherapy, Mesothelioma, Extrapleural Pneumonectomy (EPP), Histology.

Related studies

• 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)
• 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)
• Induction Therapy for Mesothelioma — I. Opitz, W. Weder (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)
• Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma — E.H. Baldini, W.G. Richards, et al. (2015)

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