Electrochemotherapy achieves high local control of lingual and tonsillar tumors in dogs and cats
Abstract
Objective
To describe local response, progression-free survival (PFS), and overall survival (OS) in dogs and cats with lingual or tonsillar tumors treated with electrochemotherapy (ECT) alone or combined with surgery.
Methods
Medical records were retrospectively reviewed for dogs and cats with a histologically or cytologically confirmed tumor of the tongue or tonsil treated with ECT alone or combined with surgery, with ≥ 1 posttreatment follow-up. Twenty-nine client-owned animals, 7 dogs and 7 cats with lingual tumors and 15 dogs with tonsillar tumors, were included. Response was assessed by modified Response Evaluation Criteria in Solid Tumors; PFS and OS were estimated by Kaplan-Meier analysis.
Results
In dogs with lingual tumors, the objective response rate (ORR) was 85.7% (complete response [CR], 71.4%); the median OS was 270 days, with 2 dogs alive at 980 and 1,090 days, and the median PFS was 263 days. In cats with lingual tumors, the ORR was 71.4% (CR, 57.1%), the median OS was 240 days, and all cats died, most of local progression; the median PFS was 215 days. In dogs with tonsillar tumors, the ORR was 80.0% (CR, 66.7%), the median OS was 240 days, and all dogs died, predominantly of pulmonary metastasis; the median PFS was 210 days.
Conclusions
ECT can provide high local response rates in dogs and cats with lingual tumors. In dogs with tonsilar tumors, even when high local response rates are achieved, patients die predominantly from distant metastasis, warranting a multimodal treatment aproach.
Clinical Relevance
ECT achieved high local response rates in all groups. It appears most useful for function-preserving treatment for lingual tumors. The combination with surgery allows treatment of larger tumors than ECT alone. The survival of dogs with tonsillar tumors was limited by metastatic dissemination, supporting a multimodal approach.
Keywords: electroporation; oral tumors; tongue; squamous cell carcinoma; malignant melanoma
Oral tumors account for approximately 6% of all neoplasms in dogs and are the fourth most common type of canine cancer. The most frequently diagnosed malignant oral tumors include malignant melanoma, squamous cell carcinoma (SCC), and fibrosarcoma. Although less common in cats, oral tumors are also clinically important, with SCC representing the predominant oral malignancy. Treatment is often challenging because complete surgical excision may be limited by the complex anatomy of the oral cavity and the need to preserve essential functions, such as prehension, mastication, swallowing, and grooming.1,2
Among oral neoplasms, tumors involving the tongue and palatine tonsils present distinct clinical challenges. Lingual tumors are relatively uncommon and include SCC, malignant melanoma, sarcoma, mast cell tumor, and other less frequent histologic subtypes. Prognosis depends not only on histology but also on tumor location as rostral lingual tumors generally have lower metastatic potential and are more amenable to complete excision than tumors arising in the caudal tongue. In contrast, canine palatine tonsillar SCC is highly aggressive and is characterized by early regional lymph node involvement and frequent pulmonary metastasis, resulting in a poor prognosis despite local treatment. Large retrospective studies1,3 have reported median survival times ranging from 126 to 243 days for dogs with tonsillar carcinoma, with substantially longer survival observed only in patients without metastatic disease at diagnosis.
Current treatment options for oral tumors include surgery, radiation therapy, chemotherapy, cryotherapy, and immunotherapy or multimodal treatment depending on tumor type, location, and stage. Surgery remains the preferred treatment for many localized oral tumors; however, extensive glossectomy or resection of caudal oral structures may result in considerable functional morbidity. Radiation therapy provides an effective alternative in select patients but is not universally available and may be associated with significant cost, logistical limitations, and side effects. Consequently, less invasive local treatment modalities capable of preserving oral function are of increasing clinical interest.1,2
Electrochemotherapy (ECT) combines the administration of a cytotoxic drug, most commonly bleomycin, with the application of short electric pulses that transiently increase cell membrane permeability, thereby enhancing intracellular drug uptake. Current veterinary guidelines support ECT as a safe and effective local ablative treatment for select superficial and oral tumors, particularly when surgery or radiation therapy is not feasible. Clinical studies have demonstrated high local response rates in canine oral malignant melanoma and nontonsillar oral SCC, especially in small tumors without bone involvement, while preserving surrounding tissues and minimizing treatment-related morbidity. Nevertheless, evidence specifically addressing tumors of the tongue and palatine tonsils remains scarce and is largely limited to small case series and isolated reports.2–4
Therefore, the objective of this retrospective case series was to describe treatment response, local tumor control, progression-free survival (PFS), and overall survival (OS) in dogs and cats with lingual and palatine tonsillar tumors treated with ECT either as a sole local treatment or in combination with cytoreductive surgery and adjuvant therapy.
Methods
This retrospective study involved review of medical records from client-owned animals treated as part of routine clinical care. Institutional Animal Care and Use Committee approval was not required. Written informed owner consent for treatment was obtained before all procedures.
Study design and case selection
A dual-center retrospective case series was conducted including dogs and cats with tumors involving the tongue (including the sublingual region) or palatine tonsil that were treated with ECT for local tumor control either as a sole treatment modality or in combination with surgery and/or adjuvant therapy.
Data were retrospectively extracted from the medical records of all eligible patients that were treated from November 2015 through December 2025. For each animal, the following information was recorded: signalment (species, breed, sex, and age); tumor characteristics, including histologic diagnosis, tumor grade, and anatomic location; and treatment details, including the local treatment administered and whether concurrent chemotherapy was given. Outcome variables comprised local tumor response, local progression, PFS, OS, patient status (alive or dead) at the last follow-up, and, when applicable, the cause of death (categorized as local progression, metastatic disease, or a cause unrelated to the tumor). Local response was assessed using modified Response Evaluation Criteria in Solid Tumors, and survival times were calculated from the date of the first ECT session.
Dogs and cats were eligible for inclusion if they had a cytologically or histologically confirmed tumor involving the tongue (including the sublingual region) or the palatine tonsil, were treated with ECT for local tumor control (either as the sole local treatment modality or in combination with surgery and/or adjuvant therapy), and had at least 1 follow-up evaluation after treatment to allow assessment of local tumor response and outcome. Animals that did not meet the above criteria, as well as those with benign tumors, were excluded. The presence of metastatic disease was not considered an exclusion criterion. After application of these criteria, the lingual group comprised 14 patients (7 dogs and 7 cats), and the tonsillar group comprised 15 patients (all dogs). Because the 2 anatomic sites differ in biological behavior, results were analyzed and reported separately by site, with dogs and cats pooled within each group.
Pretreatment evaluation and clinical staging
All patients underwent a complete physical examination, with particular attention to the oral cavity and regional lymph nodes. A CBC and serum biochemical profile were performed in all patients. Tumor staging included cytologic evaluation of regional lymph nodes when accessible and thoracic imaging (thoracic radiography or CT) to assess for metastatic disease. Tumor stage was assigned according to the WHO Tumor, Node, Metastasis (TNM) classification for oral tumors when sufficient clinical and diagnostic information was available in the medical records.
ECT protocol
Electrochemotherapy was performed under general anesthesia according to current veterinary guidelines and standardized operating procedures for veterinary ECT.5,6
Bleomycin (Bleocris 15; LKM or Hikma Pharmaceuticals) was administered IV as a bolus at a dose of 15,000 IU/m2. Electric pulse delivery began 5 to 8 minutes after IV bleomycin administration using needle electrodes connected to a BIOTEX EPV 300 electroporator (BIOTEX SRL) or a CliniVet (IGEA).
The electrodes used were needle electrodes, consisting of 8 needles separated 4 mm from each other, and pulse configuration was eight 100-µs-long pulses with a 1,000-V/cm voltage-to-distance ratio at 5,000 Hz.
Treatment planning was designed to ensure complete coverage of the tumor volume together with an appropriate margin of surrounding peritumoral tissue. In patients exhibiting partial response (PR) or local recurrence, additional ECT sessions were performed when tumoral relapse was observed.
Antiemetics and NSAIDs at appropriate doses according to the patient were administered for pain control after the procedure.
Surgical and adjuvant treatments
When complete surgical excision was not feasible but cytoreduction was achievable, partial or subtotal glossectomy or tonsillectomy and then ECT immediately after resection (surgery plus ECT protocol) was performed.
Based on histologic diagnosis and metastatic risk, select patients also received systemic or locoregional adjuvant therapy, including carboplatin, NSAIDs, immunotherapy, or lomustine, according to the attending clinician’s judgment.
Response evaluation and outcome measures
Patients were reevaluated at scheduled follow-up (weekly for the first month, then monthly) visits by physical examination of the oral cavity. Tumor dimensions were measured using a digital caliper whenever feasible. In cases in which direct measurement was not possible or advanced imaging was clinically indicated and available, CT was used to assess tumor response. Clinical examination findings were integrated with imaging results when available. Retreatment was decided when a relapse or regrowth of a previously reduced lesion was observed.
Local tumor response was evaluated according to modified Response Evaluation Criteria in Solid Tumors and classified as complete response (CR), PR, stable disease, or progressive disease (PD). The objective response rate (ORR) was defined as the proportion of patients achieving either CR or PR.7 To assess side effects, the Veterinary Cooperative Oncology Group–Common Terminology Criteria for Adverse Events was used.
Clinical outcomes included OS, defined as the interval from treatment initiation until death from any cause, and PFS, defined as the interval from treatment initiation until documented local progression. Final patient status and cause of death were recorded and classified as tumor-related (local progression or metastatic disease) or unrelated to the neoplasm.
Statistical analysis
Continuous variables were summarized as medians and ranges (minimum to maximum) and categorical variables as absolute and relative frequencies. The analysis was descriptive. All histologic types were pooled within each group. Because feline and canine oral tumors differ in biological behavior, lingual tumors were analyzed separately for dogs and cats; tonsillar tumors comprised dogs only. Overall survival and PFS were estimated by the Kaplan-Meier method, with animals alive at last follow-up censored at that date; because the 3 groups represent distinct populations, no between-group comparisons were performed. Analyses were conducted with the lifelines package for Python (version 3.12.3; Python Software Foundation). Survival times are expressed in days.
Because of the limited sample size and the marked heterogeneity of tumor histology and species, statistical analyses were considered primarily exploratory and descriptive.
Results
The study population comprised 29 client-owned animals distributed across 3 groups. The lingual tumor group in dogs included 7 animals with a median age of 11 years (range, 7 to 12 years), comprising 4 spayed females, 2 castrated males, and 1 intact male; represented breeds were Labrador Retriever (n = 3) and 1 each of mixed breed, Miniature Schnauzer, Goldendoodle, and Pomeranian. Histologic diagnoses in this group were SCC (n = 4) and 1 each of hemangiosarcoma, melanoma, and soft tissue sarcoma. The lingual tumor group in cats included 7 animals with a median age of 10 years (range, 7 to 15 years), comprising 5 castrated males and 2 spayed females; breeds were domestic shorthair (n = 4), mixed breed (2), and Siamese (1), and histologic diagnoses were SCC (5) and 1 each of soft tissue sarcoma and mast cell tumor. The tonsillar tumor group comprised 15 dogs with a median age of 11 years (range, 7 to 15 years), including 8 males (5 castrated, 3 intact) and 7 females (5 spayed, 2 intact); represented breeds included mixed breed (n = 3) and Poodle (2), with several other breeds represented by a single animal each. Histologic diagnoses in the tonsillar group were SCC (n = 8), melanoma (6), and soft tissue sarcoma (1). Tumor size was available for all 29 patients, whereas complete TNM staging was missing in 8 cases owing to the retrospective design, although the complete tumor-size data allow local response to be described for the entire cohort.
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