Interstitial Photodynamic Therapy Following Palliative Radiotherapy for Patients with Inoperable Malignant Central Airway Obstruction

Summary Patients with extrabronchial tumors that induce malignant central airway obstruction (MCAO) face significant morbidity and only 1-7 months median overall survival. An estimated 20-30% of patients with lung cancer will have MCAO during the course of their disease, but other malignancies that metastasize to the airway can induce

central airway obstruction. We have recently reported, in a Phase I study, that Photofrin® mediated image- guided interstitial photodynamic therapy (I-PDT) with our novel treatment planning and light dosimetry platform is safe, with promising outcomes. Three out of 10 treated patients are alive at 26.5, 12 and 8.3 months. Our

image-based treatment planning was used to guide the administration of the light dose rate (irradiance) and light dose (fluence) to the target tumor while sparing adjacent normal tissue. Our goal is to improve the rate of complete and partial tumor response of extrabronchial MCAO to I-PDT. To that end we propose to increase tumor blood oxygenation that will increase laser light transmission and oxygen

supply known to improve the efficacy of PDT. Murine studies reported that palliative x-ray radiotherapy (p-XRT) can increase tumor oxygenation and alter vasculature. We therefore explore the use of p-XRT to improve tumor response to I-PDT. Our preliminary data demonstrate that p-XRT followed by I-PDT (p-XRT/I-PDT) significantly

increases (p