Photodynamic Therapy as an Innovative Treatment for Malignant Pleural Mesothelioma

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Photodynamic therapy (PDT) of the pleura is an experimental treatment aimed at eradicating residual microscopic disease after macroscopic complete resection of malignant pleural mesothelioma (MPM) by means of intracavitary administration. A light-based treatment, PDT consists of 3 components: a nontoxic photosensitizing compound, oxygen, and visible light. The treatment is FDA-approved for several oncological targets, but remains experimental for MPM. PDT can be combined with lung-sparing pleurectomy and decortication and does not preclude other treatments such as adjuvant chemotherapy and/or radiation therapy. Additionally, PDT appears to bolster an immunologic effect by rendering the cancer cells that have been destroyed by the light-activated photosensitizer more presentable to the immune system. Local control and survival rates have been sufficiently rewarding to merit ongoing development of this combination of surgical technique and PDT.

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Photodynamic Therapy

PDT is a light-based cancer treatment that requires three components: a nontoxic photosensitizing compound, oxygen, and visible light.5 Most photosensitizing agents are macrocyclic structures that are chlorin- or porphyrin-based components. Chlorin, for example, is derived from chlorophyll, the compound plants use to capture energy from the sun for photosynthesis. A remarkable aspect of PDT is that each of the three components is completely innocuous alone, but the combination is lethal to

Results

Pleural PDT was first started by Pass and colleagues in the 1980s.29, 30, 31 Ultimately, in the only phase III trial to date, they performed a study comparing maximal debulking surgery and postoperative cisplatin, interferon alpha-2a, and tamoxifen immunochemotherapy with or without intraoperative PDT.32 The type of resection for patients assigned to PDT (n = 25) included 11 pleurectomies and 14 pleuropneumonectomies compared with the non-PDT group (n = 23), which included 12 pleurectomies and

Future Directions for PDT and Pleural Cancers

Given that these recent clinical studies included patients with all subtypes of mesothelioma and nodal status, we believe the local control rates and the survival rates are sufficiently promising to merit ongoing development of this combination of surgical technique and PDT. Clinical studies for the immediate future include rigorous assessment of both pulmonary function and quality of life, especially with respect to the impact of sparing the lung, pericardium, phrenic nerve, and diaphragmatic

Conclusions

PDT is an effective light-based cancer treatment that can be combined with surgery as a treatment for mesothelioma. The small, but real, depth of penetration of the treatment has allowed the technique for achieving a macroscopic complete resection to evolve to a state where natural barriers and functional structures can be preserved. Studies are under way to further evaluate the merit of this approach. In addition, we are actively engaged in research aimed at capitalizing on the unique

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