The timing of chemotherapy in the management plan for medically operable early-stage malignant pleural mesothelioma

Our plain-English summary of The timing of chemotherapy in the management plan for medically operable early-stage malignant pleural mesothelioma, by K. Shohdy, O. Abdel-Rahman (Expert Review of Respiratory Medicine, 2019).

The study

• Authors: K. Shohdy, O. Abdel-Rahman
• Journal: Expert Review of Respiratory Medicine
• Published: 2019;13(6):579-584
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Trimodality therapy (including surgery, chemotherapy and radiation therapy) represents an important management approach of early-stage malignant pleural mesothelioma (MPM). The oncological value, as well as the proper sequence of the three modalities, is still under investigations. Areas Covered: The article covers the timing of chemotherapy in the management plan with either a neoadjuvant approach or adjuvant approach. It evaluates also how to select patients for induction chemotherapy and how to assess the response to treatment. Expert Opinion: Management of patients with early-stage MPM must be completed in a multidisciplinary team in tertiary centers. Availability of newer prognostic and response assessment tools should facilitate the use of induction chemotherapy as well as the selection of patients who might benefit from radical surgery.

In plain English

This article is a narrative review, not a new study. The authors reviewed prospective and retrospective research on when to give chemotherapy to people with early-stage malignant pleural mesothelioma who are fit for surgery: before surgery (induction chemotherapy) or after it (adjuvant therapy). A systematic review they cited covered 20 studies with 793 patients. In its prospective studies, median overall survival after induction chemotherapy ranged from 16.8 to 25.5 months, and in most studies fewer than half of patients completed all planned treatment. A National Cancer Database analysis of 361 patients found similar median overall survival whether chemotherapy came before or after surgery (20.9 vs 21.7 months, p=0.500). The chemotherapy-first group had a higher 30-day mortality rate (3.3 vs 0.0). A Cochrane review by the authors' group found only two randomized trials and a lack of evidence supporting multimodality treatment. The authors concluded that randomized trials have not shown convincing added benefit of radical multimodality treatment over chemotherapy alone, and that there is no consensus on the best treatment sequence. They noted that much of the evidence is confounded by patient selection.

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 prospective and retrospective literature on treatment sequencing, plus the authors' expert opinion
• Who was studied: Published studies of patients with medically operable early-stage malignant pleural mesothelioma (MPM)
• Exposure: Not an asbestos exposure study. The subject is treatment: the timing of chemotherapy (mainly cisplatin/pemetrexed) given before or after radical surgery (extra-pleural pneumonectomy or pleurectomy/decortication), with or without radiotherapy
• Main results:
  • Reported from a systematic review the authors cited (20 studies, 793 patients). In the prospective studies, median overall survival after induction chemotherapy ranged from 16.8 to 25.5 months. In most studies fewer than 50% of patients completed the full plan.
  • Reported from a cited series of 58 patients given induction chemotherapy and extra-pleural pneumonectomy: 4 (7%) had a pathologic complete response. These patients had numerically longer survival, but the difference was not statistically significant.
  • Reported from a cited National Cancer Database analysis of 361 patients with non-metastatic MPM (182 had induction chemotherapy then resection; 179 had resection then chemotherapy). Median overall survival was similar between the two groups (20.9 vs 21.7 months, p=0.500).
  • In the same database analysis, the induction chemotherapy-first group had a higher 30-day mortality rate (printed as 3.3 vs 0.0, p=0.02, without units) and a longer post-operative hospital stay (median 7 vs 6 days).
  • Reported from a cited retrospective study of 74 patients who had extra-pleural pneumonectomy: induction chemotherapy was associated with an increased risk of postoperative acute lung injury and mediastinal shift.
  • Reported from a Cochrane meta-analysis by the authors' group: only two randomized trials were found, and the analysis showed a lack of evidence supporting multimodality treatment.
• The authors' conclusion: The authors concluded that available randomized trials have not shown convincing added benefit of radical multimodality treatment over palliative chemotherapy alone, and that there is no consensus on the best sequence of treatments for early-stage MPM.
• Limitations the authors state:
  • The authors stated that the longer survival seen with multimodality treatment in many studies is confounded by how patients were selected.
  • The authors stated that few randomized trials exist in this field.
  • The authors stated that no completed randomized study has compared upfront surgery with chemotherapy before surgery.

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: Chemotherapy, Pleural Mesothelioma, Trimodality Therapy, Multidisciplinary Team.

Related studies

• How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma? — A.J. Sharkey, K.J. O'Byrne, et al. (2016)
• PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy — B.K. Bitanihirwe, M. Meerang, et al. (2014)
• Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure — O. Rena, C. Casadio (2012)
• Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma? — S. Kim, D.A. Bull, et al. (2019)
• Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features — K. Hiroshima, T. Yusa, et al. (2009)
• Is less also better? A single-institution experience on treatment of early stage Malignant Pleural Mesothelioma — P. Bertoglio, M.C. Ambrogi, et al. (2017)

Browse more research in Expert Review of Respiratory Medicine, or return to medical research.