Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?

Our plain-English summary of Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?, by C. Munck, S.R. Mordon, A. Scherpereel, et al (The Annals of Thoracic Surgery, 2015).

The study

• Authors: C. Munck, S.R. Mordon, A. Scherpereel, H. Porte, X. Dhalluin, N. Betrouni
• Journal: The Annals of Thoracic Surgery
• Published: 2015;99(6):2237-45
• Type of article: Review
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleural photodynamic therapy after maximal surgical resection. The toxicity, effect on survival, and development of the technique were assessed. After two decades of clinical studies, intrapleural photodynamic therapy after surgical resection became a safe treatment that significantly improved the survival of patients.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This article is a review of published studies. The authors selected 16 articles, published 1991 to 2012, in which patients with malignant pleural mesothelioma had photodynamic therapy inside the chest after tumor surgery. This treatment combines a light-sensitive drug, oxygen and laser light. The 337 patients were in eleven feasibility and side-effect studies and five survival studies. In one phase III trial (25 with the therapy, 23 without), median overall survival was 14.4 versus 14.1 months, not a significant difference. In a second, with the therapy given under hyperbaric oxygen (22 with, 12 without), median survival was 15 versus 10 months, a difference the authors called significant. A retrospective study of 38 patients given lung-sparing surgery and the therapy, most also receiving chemotherapy, reported median overall survival of 31.7 months (95% confidence interval 9 to 54.3). The authors concluded that the technique has become feasible with minimum toxicity. They noted that the studies were very heterogeneous, that surgical and treatment side effects could not be separated, and that the most favorable survival results came from small nonrandomized studies. Asbestos exposure was not studied.

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: Literature review of 16 published clinical studies of intrapleural photodynamic therapy after surgery for malignant pleural mesothelioma
• Who was studied: 337 patients in total across the 16 reviewed studies (1991 to 2012), patients with malignant pleural mesothelioma treated with surgical resection; some studies also included other pleural malignancies
• Exposure: Not an asbestos exposure study; asbestos is mentioned only as background. The treatment reviewed was intrapleural photodynamic therapy, which combines a photosensitizing drug, oxygen and activating light. The drugs were m-THPC (Foscan, 20% of patients) or a hematoporphyrin such as Photofrin or Photosan (80% of patients). The therapy was given after extrapleural pneumonectomy (41.5%), pleurectomy with lobectomy (5%) or pleurectomy/decortication (53.5%)
• Main results:
  • Of the 16 reviewed studies, 11 were feasibility and toxicity studies and 5 were survival studies: two phase III studies and three retrospective studies
  • Across the reviewed studies, the maximum tolerated dose for Foscan was 0.1 mg/kg given 4 or 6 days before illumination at a light dose of 10 J/cm2. For Photofrin it was 2 mg/kg given 24 hours before illumination at 30 J/cm2, or 60 J/cm2 in the Friedberg studies
  • In the first phase III trial (Pass and colleagues; 25 patients with PDT, 23 without), there was no significant difference in median overall survival: 14.4 months with PDT and 14.1 months without
  • The second phase III study (Matzi and colleagues) evaluated intrapleural PDT under hyperbaric oxygenation after pleurectomy/decortication, with 22 patients receiving PDT and 12 not. Median survival was 15 months in the PDT group and 10 months in the no-PDT group
  • The authors described the Matzi study's difference in median overall survival as significant, in favor of PDT, despite its small size
  • In the Matzi study, local tumor recurrence after 6 months of follow-up was 9 of 22 patients in the PDT group and 10 of 12 in the no-PDT group
  • In a retrospective study (Lindenmann and colleagues), among the patients who had pleurectomy/decortication, intraoperative PDT had no significant effect on survival
  • In a retrospective study of 38 patients treated with pleurectomy/decortication and PDT (Friedberg and colleagues), 35 of 38 also received postoperative chemotherapy. Median overall survival was 31.7 months (95% confidence interval 9 to 54.3 months) at a median follow-up of 34.4 months
• The authors' conclusion: The authors concluded that, after two decades of inconclusive results, intrapleural PDT has become a feasible technique with minimum toxicity. Their abstract states that it became a safe treatment that significantly improved patient survival. They based their survival conclusion mainly on two recent studies of Photofrin-mediated PDT after lung-sparing surgery
• Limitations the authors state:
  • The 16 studies were very heterogeneous in cohort size, disease stage and subtype, type of surgery, adjuvant treatment and PDT technique, which made statistical comparison difficult
  • Toxicity caused by surgery could not be separated from toxicity caused by PDT, because most studies included only patients who received PDT after resection
  • The favorable recent survival results (the Friedberg studies) came from retrospective nonrandomized studies with small cohorts and nonstandardized adjuvant treatments
  • The first phase III trial did not include enough patients to reach statistical power
  • In the Matzi study, the specific effect of hyperbaric oxygenation could not be singled out

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, Pleural Mesothelioma, Surgical Resection.

Related studies

• Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment — N. Betrouni, C. Munck, et al. (2017)
• Photodynamic therapy for lung cancer and malignant pleural mesothelioma — C.B. Simone, K.A. Cengel (2014)
• A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma — S.R. Rice, Y.R. Li, et al. (2019)
• Response of Photofrin-sensitised mesothelioma xenografts to photodynamic therapy with 514 nm light — T.H. Foster, S.L. Gibson, et al. (1996)
• Photodynamic therapy for malignant pleural mesothelioma: the future of treatment? — J.S. Friedberg (2011)
• Functionalized Scintillating Nanotubes for Simultaneous Radio- and Photodynamic Therapy of Cancer — I. Villa, C. Villa, et al. (2021)

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