Cancer of the pleura is a virulent and lethal malignancy. Primary tumors of the pleura are rare, whereas metastatic tumors, often in the form of malignant pleural effusions, are quite common. Primary tumors of the pleura, malignant pleural mesothelioma being the most common, are typically associated with a life expectancy of less than a year. Metastatic cancers to the pleura, including non–small-cell lung cancer (NSCLC), represent stage IV disease and usually coincide with the most adverse prognosis for the primary cancer that has spread to the pleura.
The most common form of treatment for pleural cancers is systemic therapy and/or palliative care, since the majority of pleural cancers represent metastatic disease. Surgery is not typically considered an effective treatment because of the essentially impossible task of achieving a true negative margin for these cancers that coat every surface of the chest cavity. In an investigational capacity, however, surgery has become the cornerstone of highly aggressive multimodal treatment plans in selected patients, and the most widespread application in malignant pleural mesothelioma.
With the expectation that microscopic disease will remain after even the most aggressive surgical resections, one approach has been to combine an intraoperative adjuvant therapy with systemic therapy and, sometimes, adjuvant external beam radiation. The intraoperative adjuvant therapies include the following: chemotherapy, with or without hyperthermia, heated povidone iodine, radioisotopic radiation, intraoperative photon radiation, and photodynamic therapy (PDT).1 This chapter focuses on the combination of surgery and PDT and the application of this technique in malignant pleural mesothelioma.
PDT is a technique for killing tumors which uses a photosensitizer that is activated by visible light. It has been observed that photosensitizers are preferentially taken up by, or retained in, tumor cells.2,3 Once inside the cells, the photosensitizer is activated by a laser light with a wavelength specific to the sensitizer's absorption spectrum. Activation of the photosensitizer in the presence of oxygen results in the production of excited species of oxygen capable of inducing cell death. Cell death occurs by apoptosis or from direct destruction of certain cellular elements.4,5 In addition, PDT may result in neovascular damage that may compromise the tumor's blood supply.6 Finally, when PDT is used to treat cancer, it appears to enhance the host's immune response to the tumor.7,8
In addition to the presence of oxygen, the items needed to perform pleural PDT include the photosensitizer, a light source, and a dosimetry system. PDT is a dose-dependent treatment. That is, without light activation there is no effect on cells that contain the photosensitizer. The overall effect of PDT increases with the amount of activating light delivered. Although photosensitizers may demonstrate some selectivity for neoplastic cells, they also partition into normal tissues and will cause some degree of damage to those tissues when exposed to light. This is critical, ...