Current State of Pleural-Directed Adjuncts Against Malignant Pleural Mesothelioma

Our plain-English summary of Current State of Pleural-Directed Adjuncts Against Malignant Pleural Mesothelioma, by A.Y. Choi, A. Singh, D. Wang, et al (Frontiers in Oncology, 2022).

The study

• Authors: A.Y. Choi, A. Singh, D. Wang, K. Pittala, C.D. Hoang
• Journal: Frontiers in Oncology
• Published: 2022;12:886430
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Multimodality therapy including surgical resection is the current paradigm in treating malignant pleural mesothelioma (MPM), a thoracic surface cancer without cure. The main limitation of all surgical approaches is the lack of long-term durability because macroscopic complete resection (R1 resection) commonly predisposes to locoregional relapse. Over the years, there have been many studies that describe various intrapleural strategies that aim to extend the effect of surgical resection. The majority of these approaches are intraoperative adjuvants. Broadly, there are three therapeutic classes that employ diverse agents. The most common, widely used group of adjuvants are comprised of direct therapeutics such as intracavitary chemotherapy (± hyperthermia). By comparison, the least commonly employed intrathoracic adjuvant is the class comprised of drug-device combinations like photodynamic therapy (PDT). But the most rapidly evolving (new) class with much potential for improved efficacy are therapeutics delivered by specialized drug vehicles such as a fibrin gel containing cisplatin. This review provides an updated perspective on pleural-directed adjuncts in the management of MPM as well as highlighting the most promising near-term technology breakthroughs.

Copyright © 2022 Choi, Singh, Wang, Pittala and Hoang.

In plain English

This was a review of treatments applied inside the chest to extend the effect of surgery for malignant pleural mesothelioma. The authors grouped these treatments into three classes. The first was direct therapeutics, such as heated chemotherapy, povidone-iodine and interleukin-2. The second was drug delivery vehicles: a cisplatin-fibrin gel, cisplatin films, nanoparticles and a microRNA hydrogel. The third was drug-device combinations, meaning photodynamic therapy. Among the earlier studies they described, a retrospective study of 132 patients given extra-pleural pneumonectomy plus heated chemotherapy, followed by chemoradiation, reported a 75% overall recurrence rate. A phase I trial of cisplatin-fibrin gel reported median overall survival of 21 months. The only phase III photodynamic therapy trial reported median survival of 14.4 months with treatment (25 patients) and 14.1 months without (23 patients). Some vehicle methods, such as cisplatin films, had been tested only in animals. The authors noted that most studies were small and varied and that large randomized trials were lacking. They concluded that these approaches were promising and merited further investigation, with vehicle-based methods the most promising class.

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
• Who was studied: Published clinical and preclinical (animal and cell) studies of treatments applied inside the chest alongside surgery for malignant pleural mesothelioma
• Main results:
  • The authors grouped pleural-directed adjuncts into three classes: direct therapeutics, delivery vehicles carrying therapeutics, and drug-device combinations
  • A cited retrospective study of 132 patients undergoing extra-pleural pneumonectomy plus heated intraoperative chemotherapy, followed by chemoradiation, reported an overall recurrence rate of 75%
  • A cited phase I trial of cisplatin-fibrin gel in 12 non-sarcomatoid patients reported median overall survival of 21 months, median freedom from recurrence of 8 months, and recurrence in 83% of patients at 1 year
  • The only phase III trial of photodynamic therapy, as described by the authors, found no difference in median overall survival: 14.4 months with photodynamic therapy (25 patients) versus 14.1 months without (23 patients)
  • Cisplatin-loaded hyaluronate films had been studied only in animals, and human trials had not yet been conducted
  • The authors judged vehicle-based adjuncts to be the most promising class
• The authors' conclusion: The authors concluded that pleural-directed adjuncts aimed at microscopic residual disease are a promising group of approaches that merit further investigation and development
• Limitations the authors state:
  • The authors stated that the heated chemotherapy studies to date were mostly observational, retrospective and underpowered
  • The authors stated that data from large randomized trials were not available
  • The authors stated that neither of the two photodynamic therapy comparison studies they discussed had enough patients to reach statistical power

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Multimodal Therapy, Surgical Resection, Chemotherapy, Intrathoracic, Cisplatin.

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