Vacuum-assisted Electrochemotherapy: A Promising Secure Method for Intraoperative Cavity Site Margin Therapy

Abstract

Breast cancer remains a leading cause of morbidity and mortality among women globally, with approximately 2.3 million new cases annually. The standard treatment for early-stage breast cancer primarily involves breast-conserving therapy (BCT), aiming to excise the tumor along with a margin of normal tissue. Despite the precision of BCT, microscopic residual disease at the surgical margins poses a significant challenge, leading to local recurrence and metastasis if not addressed. Effective adjuvant therapies, such as whole breast radiation therapy (WBRT) and systemic treatments like chemotherapy, hormone therapy, and targeted therapy, are critical in minimizing recurrence and improving patient outcomes. However, these therapies come with significant side effects, impacting patients' quality of life. Recent advancements, including accelerated partial breast irradiation (APBI) and intraoperative radiation therapy (IORT), offer more localized treatment options but present challenges such as high costs and specialized infrastructure requirements. Electroporation-based methods, particularly electrochemotherapy (ECT), represent promising alternatives. ECT enhances drug delivery and induces cell death through electric pulses, offering a targeted approach with minimal systemic side effects. Innovations in electrode design, such as grid electrodes and image-guided insertion, have improved the efficacy of ECT for larger and internal tumors. Here, a novel vacuum-based electrode has been developed to enhance intra-operative ECT of surgically sensitive cavity site margins. This design ensures secure margin therapy by maintaining proper electrical contact through negative pressure. Finite element simulations and experimental models demonstrate the electrode's effectiveness in maximizing the ablation area while minimizing damage to healthy tissues. Preliminary results in animal models show a 98 % reduction in remaining tumor volume and prevention of metastasis. Unlike prior ECT applications that have focused on superficial or accessible tumors, this work is the first to adapt and optimize vacuum-assisted electrochemotherapy (Vac-ECT) for intraoperative non-thermal ablation of surgical cavity site margins, overcoming the limitations of conventional electrodes in the ablation of surgically sensitive/inaccessible regions and providing a practical alternative to infrastructure-heavy methods such as IORT.