C. Nwogu1, P. Pera1, K. Attwood1, W. Bshara1, R. Pandey1 1Roswell Park Cancer Institute,Buffalo, NY, USA
Introduction: Photodynamic therapy may be effective for treatment of peripheral tumors in patients unable to tolerate surgery. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, Porfimer sodium (Photofrin® or PFII), in treating human lung cancer xenografts in mice.
Methods: Patient-derived NSCLC xenografts were established subcutaneously in 20 SCID mice. There were two treatment and two control groups. Two groups of 5 mice were injected with PS1 or PFII. 24 hours later, the subcutaneous tumors in these mice were treated with laser light at a wavelength of 630nm for PFII and 665nm for PS1. 4 mice were treated with laser light with no photosensitizer and 6 mice received no treatment at all. The mice were observed for 60 days. Bonferroni adjusted methodology was used to compare the tumor growth rates between treatment groups. The tumor growth endpoint, time-to-1000mm3, was evaluated using standard Kaplan-Meier methods and compared between groups using the log-rank test. All analyses were conducted in SAS v9.3 (Cary, NC). One representative tumor in each group was cut and stained with H&E and Caspase3 to evaluate necrosis and apoptosis.
Results: Tumor re-growth pattern in the mice is illustrated in figure 1. The median time-to-1000mm3 was 12, 12, 26 and 52 days for the control, light only, PF II and PS1 groups (p<0.001). H&E analysis revealed <1%, 0%, 67% and 80% necrosis, respectively from representative samples in the same four groups. Caspase3 positivity in these groups was 2%, <1%, 17% and 39% respectively.
Conclusion:
The mice treated with PS1 exhibited a longer time for tumor regrowth, showed more tumor necrosis and apoptosis compared to the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than Porfimer sodium in treating human lung cancer xenografts in a preclinical pilot study and deserves further study.
Figure 1: Effect of photodynamic therapy on human NSCLC implanted in SCID mice
