Photodynamic therapy and the evolution of a lung-sparing surgical treatment for mesothelioma

Our plain-English summary of Photodynamic therapy and the evolution of a lung-sparing surgical treatment for mesothelioma, by J.S. Friedberg, R. Mick, M. Culligan, et al (The Annals of Thoracic Surgery, 2011).

The study

• Authors: J.S. Friedberg, R. Mick, M. Culligan, J. Stevenson, A. Fernandes, D. Smith, E. Glatstein, S.M. Hahn, K. Cengel
• Journal: The Annals of Thoracic Surgery
• Published: 2011;91(6):1738-45
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Photodynamic therapy (PDT) is a light-based cancer treatment that acts to a depth of several millimeters into tissue. This study reviewed the results of patients who underwent a macroscopic complete resection, by two different surgical techniques, and intraoperative PDT as a treatment for malignant pleural mesothelioma.

Methods: From 2004 to 2008, 28 patients with malignant pleural mesothelioma underwent macroscopic complete resection, 14 by modified extrapleural pneumonectomy (MEPP) and 14 by radical pleurectomy (RP) and intraoperative PDT. The surgical technique evolved over this period such that 13 of the last 16 patients underwent lung-sparing procedures, even in the setting of large-bulk tumors.

Results: Demographics in the MEPP and RP cohorts were similar in age, sex, stage, nodal status, histology, and adjuvant treatments. Stage III/IV disease was present in 12 of 14 patients (86%), with 50% or more with +N2 disease. The median overall survival for the MEPP group was 8.4 months, but has not yet been reached for the RP group at a median follow-up of 2.1 years.

Conclusions: In addition to the inherent advantages of sparing the lung, RP plus PDT yielded a superior overall survival than MEPP plus PDT in this series. The overall survival for the RP plus PDT group was, for unclear reasons, superior to results reported in many surgical series, especially for a cohort with such advanced disease. Given these results, we believe RP plus PDT is a reasonable option for appropriate patients pursuing a surgical treatment for malignant pleural mesothelioma and that this procedure can serve as the backbone of surgically based multimodal treatments.

Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective review looked at 28 patients with malignant pleural mesothelioma treated at the University of Pennsylvania from 2004 to 2008. All had surgery to remove all visible tumor, plus photodynamic therapy (PDT) during the operation, a treatment in which light activates a drug. Fourteen had a modified extrapleural pneumonectomy, which removed the lung, and 14 a radical pleurectomy, which spared it. Over time the technique shifted: 13 of the last 16 patients had the lung-sparing operation. In each group, 12 of 14 had stage III or IV disease. Median overall survival was 8.4 months after pneumonectomy. After pleurectomy it was not reached at a median follow-up of 2.1 years, a statistically significant difference. Disease-free survival did not differ significantly between the groups. Two pneumonectomy patients, and no pleurectomy patients, died within 30 days. The authors noted the study was small, retrospective and nonrandomized, and could not isolate PDT's effect. They called the results suggestive rather than conclusive. They concluded that lung-sparing surgery with PDT can serve as the backbone of surgery-based combined treatment. The article did not report patients' 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: Retrospective review of a single-institution surgical series comparing two operations, both combined with intraoperative photodynamic therapy. It was not randomized: the operation depended on time of enrollment, with the technique shifting toward lung-sparing surgery over the study period.
• Who was studied: 28 patients (19 men, 9 women, aged 27 to 81) with malignant pleural mesothelioma treated with surgery plus PDT at the University of Pennsylvania, 2004 to 2008. 14 had modified extrapleural pneumonectomy (MEPP) and 14 had radical pleurectomy (RP). 13 of the last 16 patients had lung-sparing procedures.
• Exposure: No asbestos exposure was reported. The treatments studied were the photosensitizing drug porfimer sodium (2 mg/kg), given 24 hours before surgery and activated during surgery by 630-nm laser light to 60 J/cm2. This was combined with either modified extrapleural pneumonectomy (lung removed) or radical pleurectomy (lung spared). Patients also received non-standardized pemetrexed-based chemotherapy and, in some cases, radiotherapy.
• Main results:
  • The RP and MEPP groups were not significantly different in sex, age, stage, nodal status, histology or adjuvant treatment. Stage III or IV disease was present in 12 of 14 (85.7%) in each group. N2 nodal disease was present in 7 of 14 RP and 9 of 14 MEPP patients.
  • A macroscopic complete resection was achieved in every patient.
  • Median overall survival in the MEPP group was 8.4 months (0.7 years in Table 3).
  • In the RP group, median overall survival had not been reached at a median follow-up of 2.1 years (range 0.5 to 4.2 years). The difference in overall survival between the two operations was statistically significant (log-rank p 0.009 in Table 3).
  • Disease-free survival did not differ significantly between the groups: the median was 1.9 years for RP and 0.6 years for MEPP (p 0.15 in Table 3).
  • Among patients with the epithelial subtype (11 RP, 6 MEPP), RP patients had significantly better overall survival and disease-free survival (p 0.03). The overall survival p value is given as 0.001 in the text and 0.0001 in Table 3.
  • Among patients with non-epithelial subtypes (3 RP, 8 MEPP), there was no statistically significant difference in overall survival (p 0.97). Median overall survival was 0.5 years for RP and 1.3 years for MEPP.
  • Two deaths within 30 days of surgery occurred in the MEPP group (one from a stroke and one from an aspiration event). None occurred in the RP group.
  • Recurrences occurred in 6 of 14 MEPP patients (2 isolated local, 2 distant, 2 both) and in 9 of 14 RP patients (6 isolated local, 1 isolated distant, 2 both).
  • Deep venous thromboses occurred in 10 of 28 patients, which the authors presumed was due to PDT. Only one pulmonary embolism was identified.
• The authors' conclusion: The authors concluded that the structure-sparing (lung-sparing) cytoreductive technique with intraoperative PDT can serve as the backbone for a surgically based multimodal treatment for malignant pleural mesothelioma. They also stated that PDT appeared of questionable, if any, benefit when combined with the lung-sacrificing procedure they performed.
• Limitations the authors state:
  • The series of 28 patients is small, which limits the study's power.
  • The study was retrospective and not randomized.
  • Chemotherapy and other adjuvant treatments were not standardized.
  • All patients received PDT, so without a non-PDT group the role of PDT in the results could not be determined.
  • The authors stated that the results should be considered suggestive rather than conclusive, and that the survival difference could be artifactual.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Histology, Median Overall Survival, Overall Survival.

Related studies

• Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma — J.S. Friedberg, M.J. Culligan, et al. (2012)
• Photodynamic therapy for mesothelioma — S.M. Hahn, R.P. Smith, et al. (2001)
• Photodynamic therapy for malignant pleural mesothelioma: the future of treatment? — J.S. Friedberg (2011)
• Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment — N. Betrouni, C. Munck, et al. (2017)
• 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)
• Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma — F. Shaikh, M.G. Zauderer, et al. (2017)

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