In low-resource settings, surgery or radiation are inaccessible to 90% of cancer patients due to inadequate infrastructure and lack of trained personnel. Resource appropriate technologies must be developed to make cancer treatments accessible. Ablative techniques, such as radiofrequency ablation are often used as a minimally invasive alternative to surgery. However, energy-based ablation techniques require expensive machinery and a steady supply of electricity and expensive consumables. To address these shortcomings, we have developed a low-cost ablation technique that stabilizes tumor growth with a simple injection of ethanol in combination with a polymer, ethylcellulose (EC). The EC injected with ethanol creates a slow-release depot of ethanol at the injection site by undergoing a solvent induced phase-transition initiated by water in tissues. EC-ethanol improves upon traditional ethanol ablation by providing increased precision while remaining low-cost and simple to administer. We evaluated the precision of EC-ethanol as well as its vascular sclerosing capabilities as a strategy to avert tumor growth in rodent models of breast cancer. EC-ethanol injected at 1 mL/hr with 6% w/w EC was used as this demonstrated to be the optimal formulation and rate for causing tumor necrosis (Morhard et al., Scientific Reports, 2017) and enhanced the anti-tumor immunostimulatory response (Nief et al., 2019, Under Review). We demonstrate the precision delivery of EC-ethanol in orthotopic 67NR mammary tumor as with small-animal MRI. Further, ethanol devascularization is monitored with photoacoustic imaging 24 hours post ablation. Local tumor control was demonstrated both in 67NR mammary tumor and in 7,12-Dimethylbenz[a]anthracene (DMBA) induced rat mammary tumor models. Repeated ablations on significantly decrease primary tumor growth compared to untreated tumors in both the mouse and rat models (P<0.05). In rats weekly 200 µL EC-ethanol injections began when tumors reached 2 mL in volume (n=5), and in 30 days tumors decreased 20% ± 3% untreated controls grew an average of 721%. For mice (n=5), 50 µL was given daily for 6 days on day 3 after tumor implantation to account for small body weight and rapidly growing tumors. Mice treated with EC-ethanol lived significantly longer (P<0.05 log-rank test) than untreated mice and mice injected with the same volume of pure ethanol. EC-ethanol is a low-cost, non-invasive tumor destruction method that shows a clear control of tumor growth when applied as a fractionated dose. We utilized a mouse and rat tumor model to ensure that the EC-ethanol's success is not dependent on the model. Ongoing studies will examine the impact of varying injected volumes at well-defined fractionation schedules on ethanol distribution, necrosis, tumor growth, and survival.
Citation Format: Corrine A. Nief, Erika Chelales, Robert Morhard, Maomao Chem, Jeffrey Everitt, Jenna Mueller, Junjie Yao, Mark W. Dewhirst, Nirmala Ramanujam. Averting tumor growth in rodent breast cancer models with a liquid ablation approach [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5243.