A Pilot Study Using Nanoparticles and Laser Induced Photothermal Ablation to Treat Low Grade Canine Mast Cell Tumors: Evaluation of Efficacy and Safety

Abstract

Background: Nanoparticles for over forty years have been the subject of a large number of physical and bioscience research. In the last decade use of these particles in medicine has gone from theoretical to clinical trials. Passive targeting of metal-based nanoparticles takes advantage of inherent abnormalities in tumor vasculature allowing accumulation in solid tumors through a process known as the ‘‘enhanced permeability and retention’’ (EPR) effect. In animal tumor implant models, combination of gold and silicone nanoparticle (GSN) and exposure of tumors to laser light (at 808nm) generated enough heat to cause tumor cell death. Mast cell tumors (MCT) are the most common skin tumor in dogs, with an estimate of MCT being roughly 20% of canine skin tumors. The goal of this pilot study is to evaluate nanoparticle and laser tumor thermal ablation on low grade canine MCT model.Results: 38 dogs with 44 mast cell tumors were enrolled in this prospective pilot study. All control tumors and those biopsied prior to laser therapy were found to be low grade MCT by histopathology (two grade method). After random number generation 8 dogs were assigned to control group and 30 dogs were assigned to treatment group. Treatment group had 36 total tumors and control group had 8 tumors present at time of enrollment. Treatment dogs had a 100% response rate, with 94% achieving clinical remission (34 tumors). Recurrence rate was 17% in those tumors achieving clinical remission. Mean progression free time (PFT) for the treatment group was 552 days and mean PFT for the control group was 1095 days.Conclusion: In conclusion results of this study suggest that photothermal ablation using gold-silicone nanoparticles and exposure to near infrared light (808 nm) provides an effective local therapy of low-grade mast cell tumors. Median progression free time and survival was not reached in our treatment group. Suggesting that long term tumor control is possible with PTA that potentially equals surgery when margins are narrow (<0.3cm) or incomplete. PTA appears to have better and more durable MCT responses than either radiation therapy and electrochemotherapy when used as sole therapies.