Article Text
Abstract
Objectives Local ablation is a promising option for recurrent localized cervical cancer in non-surgical candidates who fail platinum-based chemotherapy and radiation. We developed a low-cost polymer-assisted ethanol ablative therapy, Point-of-care Ethanol Ethyl Cellulose (PEEC), that overcomes the main shortcoming of ethanol ablation: off-target ethanol leakage. Since increased tumor coverage of ablative therapies results in reduced tumor progression and improved clinical outcomes, we hypothesized that PEEC with image-guidance would optimize cervicovaginal tumor coverage resulting in decreased tumor progression and off-target effects.
Methods A syngeneic cervicovaginal tumor model was established in C57BL/6 mice using TC1-Luc, HPV16 E6/E7+ cells expressing luciferase. Mice were randomized into image-guided PEEC (IG-PEEC), PEEC without image guidance (PEEC only), and saline ablation groups (n=5). Tumors were monitored with bioluminescence imaging via a Perkin-Elmer in vivo imaging system (IVIS) and calipers. Ablations consisted of two intratumoral injections (50mL each) of either PEEC or saline. Image-guided ablations were performed using IVIS to both target PEEC injections at regions of highest radiance intensity (correlated to tumor mass) and to assess tumor coverage.
Results Tumors treated with IG-PEEC performed best with lower total radiance, volumes and weights, and longer survival compared to PEEC only and saline groups (p < 0.05); both PEEC groups demonstrated reduced tumor growth compared to saline (p <0.05). off-target damage (ulceration) rates were lower for the IG-PEEC (n=0, 0%) versus the PEEC only (n=2, 40%) group.
Conclusions PEEC ablation enhanced by image-guidance significantly controls HPV16 E6/E7+ cervicovaginal tumor progression. This supports image-guidance as a critical component in optimizing PEEC ablation and eventual clinical translation.