Electrochemotherapy (ECT) is a local treatment used for the cytoreduction of certain solid tumors, particularly those localized in cutaneous and subcutaneous tissues. The principle of ECT is based on the increased permeabilization of cell membranes through electroporation, which enhances the penetration of chemotherapeutic cytotoxic drugs into the cells. Electroporation is achieved by delivering electric pulses via electrodes applied to the target tissue. High-voltage electric pulses alter the cell membrane potential, resulting in the rearrangement of the lipid bilayer and the formation of pores. These pores allow the passage of medium and large molecules across the membrane without specific carrier (1, 2).

Tumors of the nasal cavity has mostly epithelial origins, and represents approximately 1–2% of all the neoplasms that occur in dogs (3). These tumors primarily have a local impact, with progressive invasion of surrounding tissues and bone structures, and a lower rate of metastasis. When metastasis occurs, it typically involves regional lymphnodes and the lungs (4). Radiotherapy using high-energy megavoltage (MeV) equipment as the sole therapy is the gold standard treatment for dogs with nasal tumors. Other treatments reported include sole surgical therapies (such as conventional rhinotomy and endoscopic debridement), chemotherapy, and cryosurgery, as well as combinations of traditional or mini-invasive surgery with radiation (5–7). The safe use of ECT for the treatment of nasal cavity tumors has been reported in the literature (8, 9). In a study by Maglietti et al. (8), the procedure was performed using a single-needle electrode (SiNE) inserted directly into the affected nasal cavity without image or endoscopic guidance. The study demonstrated the feasibility of ECT for the treatment of nasal tumors, with variable therapeutic responses and minimal adverse effects.

In this case report, we describe two dogs with endoscopic, computed tomographic (CT), and histologic findings consistent with nasal tumors underwent endoscopic-guided ECT. A novel electrode, specifically designed for the treatment of deep neoplasms, was used to induce electroporation of the nasal tumors under endoscopic guidance, aiming to maximize treatment efficacy in combination with palliative metronomic chemotherapy. The owners were informed that radiotherapy is the first-line treatment for this type of tumor; however, due to financial constraints, this option was not pursued. Informed consent was obtained from all subjects involved in the study. The aim of this study is to retrospectively describe and evaluate a novel electrode for endoscopic-guided ECT in the nasal cavity, focusing on its technical feasibility, potential complications, and clinical outcomes in dogs with nasal tumors treated in combination with chemotherapy.

This report describes the treatment of canine nasal tumors using a novel electrode specifically designed for deep electroporation under endoscopic guidance, combined with adjuvant metronomic chemotherapy, which proved effective in achieving tumor cytoreduction in two dogs.

Electrochemotherapy (ECT) is a locoregional antitumor treatment increasingly used for cytoreduction of solid tumors. Its mechanism of action is based on reversible electroporation, a biophysical process in which short, high-intensity electric pulses transiently increase cell membrane permeability. These electric pulses are generated by a pulse generator and delivered to the target tissue through specifically designed electrodes (1). Electroporation facilitates the intracellular uptake of poorly permeant cytotoxic agents, which otherwise have limited ability to cross the cell membrane. Exposure of cells to pulsed electric fields induces the formation of transient aqueous pores (electropores) in the lipid bilayer, allowing diffusion of ions, water, and chemotherapeutic molecules. Additionally, electric fields promote transient clustering of transmembrane proteins, forming pseudopores that further enhance molecular transport across the membrane (1, 2). Bleomycin and cisplatin are the chemotherapeutic agents most commonly used in clinical ECT protocols and may be administered either intravenously or intratumorally. The increased intracellular drug accumulation markedly enhances local cytotoxicity, allowing effective tumor control with lower drug doses and reduced systemic toxicity. Beyond direct cytotoxicity, ECT exerts additional antitumor effects (1, 2). These include a vascular-disrupting effect, characterized initially by a reversible vascular lock with reduced tumor blood flow, followed by endothelial cell damage in small vessels, leading to prolonged ischemia (14, 15). Furthermore, tumor cell death induced by ECT promotes the release of tumor-associated antigens, contributing to immune system activation and a secondary antitumor immune response (1). Clinical oncology studies have demonstrated that ECT is effective in the treatment of cutaneous and subcutaneous tumors in both humans and animals, with a curative response observed in approximately 80% of cases (1, 16). Some studies have shown that, in certain cases, ECT can be an equivalent or even superior treatment compared to surgery for specific tumors (1, 17). In other cases, ECT is used with palliative intent, including for tumors located in areas that have been previously irradiated or surgically treated (11, 16).

Only a few previous studies have reported the use of ECT for the management of nasal cavity neoplasm (8, 9). Suzuki et al. (9) documented, for the first time, the technical application of multiple needles into the nasal cavity and the use of conductive gel via a surgical approach to achieve an appropriate electric field. To reduce the invasiveness of the procedure, Maglietti et al. (8) performed a single ECT treatment using a SiNE inserted into the nasal cavity. In this study, electroporation was performed without endoscopic guidance; only CT or magnetic resonance (MR) imaging was used to guide the procedure and prevent inadvertent penetration through the cribriform plate. In our cases, we took advantage of the low invasiveness of the single-electrode technique, one of the main benefits described by Maglietti et al. (8) through the use of a novel bipolar single electrode. However, to further improve the efficacy and safety of the procedure, we employed not only CT guidance but also direct visualization of the neoplasm through endoscopic guidance. This approach allowed us to increase the treated area, addressing one of the main limitations of the previously described technique, the inability to cover the entire tumor effectively, while also reducing the risk of electroporating healthy nasal tissue (7). As reported in recent studies, bleomycin was administered intravenously at an increased dose intensity (20,000 IU/m²) to enhance treatment efficacy (11, 12). To achieve better local control of the mass and prevent regrowth, three treatment sessions were performed at three-week intervals, following the protocol previously described by Moretti et al. (11). In fact, although ECT can be effective with a single treatment, in cases of partial tumor response it can be repeated multiple times, achieving equal or even improved effectiveness (1, 18). Finally, as recently suggested by other authors, metronomic chemotherapy was used to enhance the local effect of ECT (7).

Radiotherapy, alone or in combination with surgery, are the gold standard for treating nasal tumors; however, complete remission is rarely achieved, and most tumors only decrease in size (19). The limited availability of radiotherapy facilities and the high cost of treatment make it inaccessible for many pet owners; moreover, tumors that recur after radiotherapy often exhibit reduced sensitivity to radiation (7, 20). Many animals that experience recurrence of the neoplasm, or that are unable to undergo radiotherapy due to economic or other reasons, require alternative therapeutic options. Currently, the only available palliative treatment strategies are surgery and endoscopic debulking (7, 20). Rhinotomy is an invasive treatment that has not demonstrated a significant increase in life expectancy and is associated with a high rate of morbidity (7, 20). Endoscopic debulking with laser is a minimally invasive alternative that can be used alone or in combination with radiotherapy. The advantage of this treatment lies in the ability to ablate the neoplasm without the need for surgical access, resulting in shorter hospitalization times and faster recovery for the animals. However, multiple treatment sessions may be necessary and a complete remotion of the mass is rarely obtained (20). Endoscopic-guided ECT, as described in this report, shares similarities with endoscopic debulking; however, debulking procedures can be lengthy, lasting up to 72 min (7), whereas ECT sessions were completed in no more than 20 min, consistent with the active window of the cytotoxic chemotherapeutic agent in the bloodstream.

In our cases report, a nasal carcinoma and a transitional carcinoma were treated using endoscopic-guided ECT, resulting in a reduction in tumor size for both cases. The cytoreduction outcomes were confirmed through head CT scans and rhinoscopic examinations performed during treatment, as well as during follow-up. Head CT scans showed a decrease in tumor size and volume. Rhinoscopic examination revealed an increase in nasal cavity space, rarefaction of the nasal conchae, and a reduction in the nasal neoformation. According to Maglietti et al. (8), in which 64% of animals achieved a PR, the objective response observed in both of our cases was comparable. Considering that the antitumor effectiveness of ECT depends on tumor size, with smaller tumors responding better than larger ones, our preliminary results, in agreement with previous reports, indicate that nasal tumor reduction can also be effectively achieved through endonasal ECT (1). Although large prospective studies are limited, a recent case report describes successful partial remission of a canine nasal carcinoma treated with a long-term metronomic combination of chlorambucil and prednisolone (21). Although the exact contribution of chemotherapy as an adjuvant to local ECT treatment is unknown, additional evidence from metronomic protocols in dogs with nasal tumors demonstrates antitumor activity and clinical benefit (7), supporting the potential role of chemotherapy in the management of rhino-nasal neoplasms.

Only mild bleeding was observed as an intraoperative complication during endoscopic-guided ECT. Blood loss was managed with the application of cold water, adrenaline, and nasal tampons in the nasal cavity, along with the parenteral administration of tranexamic acid. Similar complications have been previously reported for other minimally invasive palliative treatments for nasal tumors, including endoscopic-guided procedures (20). During electroporation, a temporary vasoconstriction occurs, reducing blood flow by up to 80%. This effect helps to retain chemotherapeutic drugs within the tumor, enhancing their cytotoxic potential, while simultaneously limiting nutrient supply to the tumor and reducing the risk of hemorrhage (8, 14, 15). In the literature, severe hemorrhage has been reported as a complication during endoscopic laser debulking, obstructing the view and preventing completion of the procedure (20). In our cases, bleeding did not prevent electroporation of the mass. The blood was effectively aspirated through the endoscope’s working channel, allowing all procedures to be completed successfully.

In a study evaluating the clinical outcomes of dogs with nasal tumors treated with radiotherapy followed by endoscopic laser debulking, only 44.4% of the animals showed a significant reduction in clinical signs. Moreover, many animals were euthanized due to the severity of clinical signs that compromised their quality of life (20). In contrast, a recent study by Bottero et al. (7) identified endoscopic debridement as a valuable palliative treatment for animals with nasal tumors, due to its positive impact on quality of life. Since complete remission of endonasal tumors is not achievable with currently available treatments, the primary therapeutic goal (particularly in veterinary medicine) is the alleviation of tumor-related symptoms, while minimizing side effects as much as possible. In this case report, each dog presented with clinical signs consistent with a nasal tumor, including nasal and reverse sneezing, nasal discharge, and abnormal respiratory sounds. In the first dog, treatment led to an improvement in clinical symptoms, with only occasional hemorrhagic discharge persisting throughout the study period. In the second case, ECT resulted in a complete resolution of clinical signs for several months, with a recurrence of epistaxis occurring 131 days (≅ 4 months) after the initiation of the ECT protocol. Considering that most animals either succumb to their condition or are euthanized due to severe clinical signs, this approach provides a palliative option that improves quality of life in affected animals.

Several radiological side effects may occur following radiotherapy, particularly inflammation or infection (bacterial or fungal) of adjacent regions to the irradiated site (e.g., eyes, mouth, nasal cavity, brain etc.). In the most severe cases, these complications can become chronic and may necessitate the placement of a feeding tube for enteral nutrition (8, 20). Previous applications of ECT for the treatment of nasal neoplasms reported only one side effect (nasal passage inflammation) which was managed with a one-week course of corticosteroid therapy (8). In our cases, although moderate signs of local inflammation (e.g., edema, hyperemia, presence of eschar) were observed during endoscopic inspection throughout the ECT sessions, no clinical signs of inflammation were reported, and no additional treatment was required. This favorable outcome may be attributed to the concurrent administration of piroxicam throughout the study period, used as an adjuvant to chemotherapy. At the same time, the selective electroporation of only the affected tissue (ensured by endoscopic guidance) may contribute to a reduction in local inflammation.

The overall mean survival time for dogs treated with radiotherapy ranges from 8 to 19 months, whereas the mean survival time after surgery or chemotherapy without irradiation, or in the absence of treatment, is 3–6 months (19, 22, 23). The mean survival time for dogs treated with a combination of radiation and laser debulking was 18 months (20). Similar results were reported in the only study that used ECT for the treatment of nasal tumors, where the overall mean survival time was 16.86 months (8). In our experience, one dog died spontaneously 99 days after the initiation of treatment with endoscopic-guided ECT, due to unknown causes that appeared unrelated to the tumor pathology. The total survival time for this dog, calculated from the time of diagnosis, was 162 days (≅ 5.5 months). Another dog was euthanized due to recurrence of severe clinical signs related to the tumor at 208 days from the first ECT session, with a total survival time from diagnosis of 274 days (≅ 9 months). Unfortunately, the available data are limited and do not allow for a reliable comparison of survival time after endoscopic-guided ECT with other treatments reported in the literature. However, both our findings and those of Maglietti et al. (8) are promising and underscore the need for further studies involving larger cohorts of dogs and extended follow-up periods.

The principal limitations of this case report are its retrospective nature and the small number of treated animals, which preclude statistical analysis and definitive conclusions. In addition, the combined use of local ECT and metronomic chemotherapy does not allow the specific contribution of ECT to be precisely determined, as the observed clinical response may have been influenced by the concomitant medical therapy. Considering the deep localization of nasal tumors, which often precludes curative surgical excision with clear margins, and the high cost of radiotherapy, endonasal ECT using a specifically designed electrode, in combination with adjuvant metronomic chemotherapy, may represent an effective palliative treatment option. In the treated animals, this approach resulted in tumor size reduction and improvement of clinical symptoms. Further studies involving larger cohorts, as well as investigations assessing the efficacy of endonasal ECT alone and in combination with other treatments, particularly endoscopic debulking and metronomic chemotherapy, are needed. Such studies would support the development of a standardized and reproducible protocol, similar to those established for other solid cutaneous and subcutaneous tumors.