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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087971-10
Application #
8555156
Study Section
Special Emphasis Panel (ZCA1-GRB-P (O1))
Project Start
2000-07-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
10
Fiscal Year
2012
Total Cost
$155,884
Indirect Cost
$56,688
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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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