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; Darafsheh, Arash; Ahmad, Mahmoud et al. (2016) PDT Dose Dosimeter for Pleural Photodynamic Therapy. Proc SPIE Int Soc Opt Eng 9694:96940Y
Sterman, Daniel H; Alley, Evan; Stevenson, James P et al. (2016) Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy. Clin Cancer Res 22:3791-800
Ong, Yi Hong; Zhu, Timothy C (2016) Analytic function for predicting light fluence rate of circular fields on a semi-infinite turbid medium. Opt Express 24:26261-26281
Ghogare, Ashwini A; Miller, Joann M; Mondal, Bikash et al. (2016) Fluorinated Photodynamic Therapy Device Tips and their Resistance to Fouling for In Vivo Sensitizer Release. Photochem Photobiol 92:166-72
Grossman, Craig E; Carter, Shirron L; Czupryna, Julie et al. (2016) Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity. Int J Mol Sci 17:
Penjweini, Rozhin; Kim, Michele M; Dimofte, Andrea et al. (2016) Deformable medical image registration of pleural cavity for photodynamic therapy by using finite-element based method. Proc SPIE Int Soc Opt Eng 9701:970106
Zhu, Timothy C; Lu, Amy; Ong, Yi-Hong (2016) An improved analytic function for predicting light fluence rate in circular fields on a semi-infinite geometry. Proc SPIE Int Soc Opt Eng 9706:97061D
Penjweini, Rozhin; Kim, Michele M; Liu, Baochang et al. (2016) Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling. J Biophotonics 9:1344-1354
Penjweini, Rozhin; Kim, Michele M; Finlay, Jarod C et al. (2016) Investigating the impact of oxygen concentration and blood flow variation on photodynamic therapy. Proc SPIE Int Soc Opt Eng 9694:
Gemmell, Nathan R; McCarthy, Aongus; Kim, Michele M et al. (2016) A compact fiber-optic probe-based singlet oxygen luminescence detection system. J Biophotonics :

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