Photodynamic therapy for the treatment of non-small cell lung cancer

Abstract

Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

Keywords: Photodynamic therapy; endobronchial; lung cancer; non-small cell lung cancer; palliative care.

Figure 1.. A photosensitizer (¹PS) is administered systemically or topically to a patient prior to the application of a laser or incandescent light (hv) directed to the region of interest. This light is typically between 600-800 nm within the optical window of tissue, and the light source is dependent on the photosensitizer absorption, disease location, tumor size and accessibility, and tissue characteristics. The absorption of light causes the photosensitizer with two electrons in the ground state with opposite spin to transfer one electron to a higher energy orbital, generating an unstable excited photosensitizer (¹PS*). This excited photosensitizer can emit excess energy as fluorescence and/or heat, or it may develop into an intersystem crossing that forms a more stable triplet state (³PS*) with inverted spin of one electron. Reactive oxygen species that mediate photodynamic therapy cytotoxicity can then be generated through two processes. A Type II process, which is the most common process governing photosensitizers in photodynamic therapy and predominates in normoxic conditions, can occur when the triplet state photosensitizer decays to a ground state or transfers its energy to molecular oxygen (O₂), resulting in the formation of excited state singlet oxygen (¹O₂) and regenerating the ground-state photosensitizer. Singlet oxygen can reacts with the substrate (S) to generate oxidized products. Alternatively, a Type I process can occur when the triplet state photosensitizer reacts directly with an organic molecule or substrate to produce a radical or radical ion both in the photosensitizer and the substrate. The substrate typically donates an electron to the sensitizer, resulting in a substrate radical cation (S+) and a photosensitizer radical anion (PS-). Although a type I reaction can occur during hypoxic conditions, in the presence of oxygen the reduced photosensitizer can undergo autoxidation with oxygen (O₂) to generate a superoxide anion radical (O₂-), regenerating the ground-state photosensitizer.