Project 5 Patients with non-small cell lung cancer (NSCLC) and pleural spread have a median survival of 6 to 9 months which is similar to patients with distant metastatic spread. An exploratory trial of Photofrin-mediated PDT in patients with NSCLC and pleural spread has recently demonstrated excellent local control and a median survival of 22 months. In this application, we propose to evaluate further pleural PDT for NSCLC and conduct studies that will lead to optimization of this approach.
The specific aims of this project are to 1) to perform a Phase II clinical trial of intrapleural Photofrin-mediated PDT in patients with stage 1MB NSCLC defined by pleural dissemination 2) to assess Photofrin levels and tumor oxygenation in tumor from patients with NSCLC and assess PDT-induced changes in molecular signaling pathways, 3) to optimize a murine model of NSCLC pleural carcinomatosis and characterize the molecular consequences of PDT and 4) to develop new strategies for light delivery and light production that can be translated into future clinical studies. The significance of the clinical study is, if the preliminary clinical results are confirmed, then a novel therapeutic approach would be available for a patient population which has a poor prognosis. The correlative studies of Photofrin uptake and hypoxia and the characterization of signaling pathway response to PDT in preclinical models and human tissues will be used in future studies to develop ways to improve the therapeutic index for pleural PDT.
|Kim, Michele M; Ghogare, Ashwini A; Greer, Alexander et al. (2017) On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling. Phys Med Biol 62:R1-R48|
|Friedberg, Joseph S; Simone 2nd, Charles B; Culligan, Melissa J et al. (2017) Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years. Ann Thorac Surg 103:912-919|
|Penjweini, Rozhin; Kim, Michele M; Zhu, Timothy C (2017) Three-dimensional finite-element based deformable image registration for evaluation of pleural cavity irradiation during photodynamic therapy. Med Phys 44:3767-3775|
|Ahn, Peter H; Finlay, Jarod C; Gallagher-Colombo, Shannon M et al. (2017) Lesion Oxygenation Associates with Clinical Outcomes in Premalignant and Early Stage Head and Neck Tumors Treated on a Phase 1 Trial of Photodynamic Therapy. Photodiagnosis Photodyn Ther :|
|Yan, Lesan; Miller, Joann; Yuan, Min et al. (2017) Improved Photodynamic Therapy Efficacy of Protoporphyrin IX-Loaded Polymeric Micelles Using Erlotinib Pretreatment. Biomacromolecules 18:1836-1844|
|Penjweini, Rozhin; Kim, Michele M; Liu, Baochang et al. (2017) Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling [J. Biophotonics 9, No. 11-12, 1344-1354 (2016)]. J Biophotonics 10:473-474|
|Kennedy, Gregory Thomas; Newton, Andrew; Predina, Jarrod et al. (2017) Intraoperative near-infrared imaging of mesothelioma. Transl Lung Cancer Res 6:279-284|
|Zhu, Timothy C; Kim, Michele M; Ong, Yi-Hong et al. (2017) A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT. Proc SPIE Int Soc Opt Eng 10047:|
|Gemmell, Nathan R; McCarthy, Aongus; Kim, Michele M et al. (2017) A compact fiber-optic probe-based singlet oxygen luminescence detection system. J Biophotonics 10:320-326|
|Kim, Michele M; Penjweini, Rozhin; Zhu, Timothy C (2017) Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy. J Biomed Opt 22:28002|
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