Development of enhanced ethanol ablation as an alternative to surgery in treatment of superficial solid tumors

Abstract

While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.

Apoptotic and cytotoxic effects on human glioblastoma cell lines induced by essential oil Lavandula Augustifolia

“…This study proved that the tumour volume injected with the thickened treatment solution verses the unmodified decreased to 32 ± 34% (mean ± s.d.) of the initial volume . An enhanced topical delivery of EOla, that is intra‐cavitational application with 1:100 diluted EOla in thickened solution, is the direction for future investigation in in vivo studies and Phase I clinical trial for minimizing the effect of necrosis in the tumour and surrounding tissues at the site of lesion.…”

“…of the initial volume. 18 An enhanced topical delivery of EOla, that is intra-cavitational application with 1:100…”

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model

“…We hypothesize that EC will increase the time that ethanol is held at the injection site in an intratumoral depot, and as the ethanol remains in contact with the target-tissue longer it will increase local necrosis. In previous studies we characterized the rheological properties of the gel produced by EC-ethanol (22) and its delivery into ex vivo tissue (23). We previously demonstrated that 3% EC-ethanol forms a fibrous gel upon contact with water and in superficial hamster cheek pouch tumors decreased tumor volume observed over a 7 day period compared to pure ethanol (22).…”

Modeling of drug diffusion in a solid tumor leading to tumor cell death

“…For the past decade there have been numerous studies on the safety and efficacy of ethanol ablation for different types of tumors [8,9,10,11,12]. Some major drawbacks of the technique include the need for multiphase treatments, large amounts of fluid, and the rapid escape of ethanol in non-capsulated tumors [13]. Traditionally these drawbacks were greater for larger tumors, but more recently it has been shown by Kuang et al [11] that a single-session high-dose ethanol injection can ablate hepatocellular carcinoma tumors of diameters up to 5 cm.…”

“…Recently, Morhard et al [13] developed a new method employing ethyl cellulose for which single-phase small-volume treatments suffice to trigger ablation. Their goal is to maximize distribution of the ethanol throughout the tumor while minimizing the necessary solution volume.…”