Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions

Abstract

Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.

Keywords: interstitial photodynamic therapy; intraoperative photodynamic therapy; non–small cell lung cancer; photodynamic therapy.

Figure 1.

(A) An optical fiber with 20-mm cylindrical diffuser end (Optiguide Fiber Optic; CuraScript/Pinnacle Biologics, Chicago, IL). (B) This bronchoscopic image shows the photodynamic therapy (PDT) catheter (arrow) during illumination of the left upper lobe and distal left main stem to treat the carcinoma in situ. (C) Bronchoscopic image showing the mucus sloughing of the distal left main stem and the left upper lobe (arrow) 2 days post PDT. (D) Bronchoscopic image showing the distal left main stem and left upper lobe 4 weeks post PDT.

Figure 2.

Tumor epithelial cells were isolated and enriched by proliferation under selective culture conditions in vitro. (A) Phase contrast image of tumor cell and fibroblast (×100). (B) Fluorescence image of the fibroblast stained with carboxyfluorescein succinimidyl ester dye. (C) Fluorescence image of the 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a. The image on the right shows preferential retention of this photosensitizer 24 hours after the initial exposure.

Figure 3.

 (A) Procedure involving light illumination of the thoracic cavity during intraoperative photodynamic therapy (PDT). (B) Balloon device used to deliver diffused laser light within the cavity. Although this is a therapeutic red light, the high intensity is shown as bright white light. (C) The isotropic probes (arrow) in a transparent tube secured with a suture within the cavity, before PDT. (D) Portable laser and light dosimetry system. Each detector is marked with its location, in this exemplary case (from left to right): Apex, posterior mediastinum (PM), pericardium (PERI), diaphragm (DIA), pulmonary hilum (PH), posterior diaphragmatic sulcus (PS), anterior diaphragmatic sulcus (AS), anterior mediastinum (AM).

Figure 4.

Response of TEC-1-2 lung tumor epithelial cells to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH) photodynamic therapy by (A) crosslinking signal transducer and activator of transcription-3 (STAT3), and (B) inducing cell death as measured 24 hours later. Ctl = control; PS = photosensitizer.