Electrochemotherapy Research Articles

Clinical Insights and Future Prospects: A Comprehensive Narrative Review on Immunomodulation Induced by Electrochemotherapy.

Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects-the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT's potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers.

Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study

BackgroundThis study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). MethodsWe audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006–2020) within the International Network for Sharing Practices of ECT (InspECT). Results452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1–8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. ConclusionsAmong patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.

Application of Gold Nanoparticles for Improvement of Electroporation-Assisted Drug Delivery and Bleomycin Electrochemotherapy.

Background/Objectives: Electrochemotherapy (ECT) is a safe and efficient method of targeted drug delivery using pulsed electric fields (PEF), one that is based on the phenomenon of electroporation. However, the problems of electric field homogeneity within a tumor can cause a diminishing of the treatment efficacy, resulting only in partial response to the procedure. This work used gold nano-particles for electric field amplification, introducing the capability to improve available elec-trochemotherapy methods and solve problems associated with field non-homogeneity. Methods: We characterized the potential use of gold nanoparticles of 13 nm diameter (AuNPs: 13 nm) in combination with microsecond (0.6-1.5 kV/cm × 100 μs × 8 (1 Hz)) and nanosecond (6 kV/cm × 300-700 ns × 100 (1, 10, 100 kHz and 1 MHz)) electric field pulses. Finally, we tested the most prominent protocols (microsecond and nanosecond) in the context of bleomycin-based electrochemotherapy (4T1 mammary cancer cell line). Results: In the nano-pulse range, the synergistic effects (improved permeabilization and electrotransfer) were profound, with increased pulse burst frequency. Addi-tionally, AuNPs not only reduced the permeabilization thresholds but also affected pore resealing. It was shown that a saturated cytotoxic response with AuNPs can be triggered at significantly lower electric fields and that the AuNPs themselves are non-toxic for the cells either separately or in combination with bleomycin. Conclusions: The used electric fields are considered sub-threshold and/or not applicable for electrochemotherapy, however, when combined with AuNPs results in successful ECT, indicating the methodology's prospective applicability as an anticancer treatment method.

Electrochemotherapy with intravenous, intratumoral, or combined administration of bleomycin in the treatment of colorectal hepatic metastases in a rat model

Electrochemotherapy (ECT) combines the reversible electroporation (rEP) with intravenous (i.v.) or intratumoral (i.t.) administration of chemotherapeutic drugs. We conducted this study to compare the efficacy of i.v., i.t., and i.v. + i.t. injection of bleomycin (BLM) in ECT treatment of colorectal hepatic metastases in a rat model. WAG/Rij rats were randomized into three groups and underwent ECT with i.v., i.t., or i.v. + i.t. injection of BLM. Tumor volumes and oxygenation were measured by means of ultrasound and photoacoustic imaging. Moreover, liver and tumor tissue were analyzed by histology and immunohistochemistry. The i.v. and i.v. + i.t. groups exhibited a 44.0% and 46.6% reduction in oxygen saturation of the tumor tissue when compared to pretreatment values, whereas the i.t. group only showed a reduction of 35.2%. The extent of tumor tissue necrosis did not statistically differ between the groups. However, the i.t. group showed a tendency towards a lower necrosis rate. Cell proliferation, apoptotic cell death, vascularization, and immune cell infiltration were comparable in the treated tumors of the three groups. ECT with i.v. administration of BLM should be preferred in clinical practice, as the combined i.v. + i.t. therapy did not show superior oncological outcomes in the present study.

Comparison of Three Chemotherapy Protocols With Electrochemotherapy for the Treatment of Feline Cutaneous Squamous Cell Carcinoma.

Electrochemotherapy (ECT) with intravenous (IV) and/or intratumoral (IT) bleomycin has shown considerable efficacy in the treatment of non-resectable feline cutaneous squamous cell carcinoma (cSCC), boasting response rates of up to 95%, but other chemotherapy protocols have not yet been investigated. The objective of this prospective multicentre study was to compare the overall response rate (ORR) and progression-free interval (PFI) between cats with cSCC treated with ECT using IT and IV carboplatin (IV + IT), IV carboplatin (IV) or IV bleomycin (IV). A total of 44 cats with unresectable cSCC across three centres were enrolled and treated with ECT using carboplatin IV + IT (n = 10), carboplatin IV (n = 11) or bleomycin IV (n = 23). Treatment response according to RECIST criteria was recorded at 2 and 4 weeks post-treatment, and patients were followed until disease progression and/or death. All three groups were comparable regarding age, sex, weight, and lesion size. Adverse events were generally mild, localised and similar between groups. ORRs were 90.0% (carboplatin IV + IT), 90.9% (carboplatin IV) and 95.6% (bleomycin IV) and were not significantly different (p = 0.79). Median PFI was not reached for carboplatin IV + IT or carboplatin IV and was 566 days for bleomycin IV, with no significant difference between the three groups (p = 0.81). This study suggests that ECT using IV or IV + IT carboplatin is a reasonable alternative therapeutic option for managing cSCC, and further studies are warranted to compare outcomes between treatment protocols.

Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model.

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.

Description of outcome and adverse events in 21 cats with locally advanced nasal planum squamous cell carcinoma treated with electrochemotherapy.

Squamous cell carcinoma (SCC) is the most common tumour in the nasal planum of cats. Surgery has traditionally been the treatment of choice but might not be feasible in locally advanced scenarios. Electrochemotherapy (ECT) has shown good control in superficial tumours, but there is a lack of robust information about efficacy in locally advanced cases. The aim of this study was to assess the safety and efficacy of ECT in the treatment of locally advanced stage nasal planum SCC in cats. The clinical database of a veterinary referral hospital was searched retrospectively for cats diagnosed with a locally advanced nasal planum SCC (T3N0M0 or T4N0M0) that had received ECT. Local response, adverse events and outcome were documented. The data were evaluated by inferential statistics and correlations between response, recurrence, feline immunodeficiency virus/feline leukaemia virus status, number of treatments, voltage and severity of adverse events, with Kaplan-Meier curves and log-rank tests. Statistical significance was set at P <0.05. In total, 21 cats were enrolled over a 4-year period. Nineteen cats achieved a complete response (CR) and two cats a partial response (PR) for an overall response rate of 100%. Cats achieving a CR had a median disease-free interval of 182 days (range 128-327) and those with a PR had a median progression-free survival of 156.5 days (range 122-191). The median time to progression was not reached. The overall survival was 453 days for a median follow-up of 341 days (range 191-989). Of the cats, 62% had grade 3 or 4 toxicities, but no deaths due to the treatment were documented. Only voltage was correlated with longer survival (P = 0.001). ECT appears to be an effective treatment for feline nasal planum SCC and could be considered a first-line therapy for locally advanced cases. Toxicities reported can be severe in the short term and these could be secondary to more invasive lesions and equipment used.

The Long-Term Results of Electrochemotherapy in the Treatment of Patients with Locoregionally Advanced, Unresectable Melanoma.

Background/Objectives: Despite observing progress in recent years in the treatment of patients with advanced melanoma, the optimal management of locoregional recurrence has not been determined. Various methods are used to treat this group of patients. One of these methods is electrochemotherapy. The present study presents the distant results in treating patients with the locoregional recurrence of melanoma, using the technique of electrochemotherapy. Methods: This study includes a retrospective analysis of 88 patients' data with locoregional melanoma recurrence, treated with electrochemotherapy (ECT) between 2010 and 2023, in two reference centers. Results: Approximately 80% of patients responded to the ECT treatment, achieving partial or complete remission. In a multivariate analysis, statistically significant longer overall survival was found in the group of patients who achieved complete remission after ECT and were treated with immunotherapy. Discussion: The results may suggest the existence of synergy between ECT and immunotherapy. However, confirmation of this fact requires further prospective studies that will also establish the role of ECT in the combination treatment of patients with locoregional recurrence of melanoma.

The role of electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinoma: long-term results.

While electrochemotherapy (ECT) is increasingly utilized as a highly effective method in the treatment of tumors in the head and neck region, there is significantly less data available for eyelid-periocular skin tumors. Our group reported the first extensive case series of eyelid-periocular basal cell carcinoma (BCC) patients with short-term follow-up treatment with ECT. The present study aims to report our long-term results of eyelid-periocular BCC cases treated with ECT. The treatments were performed according to the ESOPE (European Standard Operating Procedures on Electrochemotherapy) guidelines using the Cliniporator™ device. All patients received bleomycin-based ECT, administered intratumorally or intravenously. Tumor response was evaluated using the RECIST 1.1 criteria. The results of 19 patients treated with ECT are presented. Four patients had locally advanced primary tumors, while 15 patients had recurrent tumors. Bleomycin was administered intratumorally in four patients and intravenously in 15 patients. The overall response was 100%, while the complete response rate proved to be 95%. In three cases (15.8%), recurrence was observed during the mean follow-up period of 78.9 months. ECT can effectively treat locally advanced or recurrent BCC in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with long interval follow-up.

Perineural invasion as a predictor of local recurrence in cats with squamous cell carcinoma treated with electrochemotherapy.

Squamous cell carcinoma (SCC) is a malignant neoplasm that accounts for approximately 15-25% and 70-80% of all feline cutaneous and oral tumors, respectively. Similar to that in humans, feline SCC can be highly invasive locally; however, its metastasis rate is low. Thus, effective local treatment may be curative for most patients, and includes surgery, electrochemotherapy (ECT), cryosurgery, or a combination of these. However, this neoplasia can manifest more aggressively in some patients, leading to higher recurrence rates. In humans, perineural invasion (PNI) has been described as a relevant tumor dissemination pathway associated with high-risk SCC, resulting in higher recurrence rates, resistance to local treatments, and short survival. However, PNI and its prognostic value have not been described in feline SCC. This study aimed to evaluate the PNI in a feline population with SCC treated with ECT and correlate its presence with the occurrence of local recurrence and other clinical variables. Twenty-four cats histopathologically diagnosed with SCC between 2013 and 2021 were retrospectively selected from the medical records of the Oncological Center Vet Cancer (São Paulo, SP, Brazil). The inclusion criteria were ECT as the sole therapy, histopathological evaluation of PNI, and absence of distant metastatic disease. The complete response rate was 96% (23/24), and PNI was identified in 33% of the cats (8/24, PNI-positive group), whereas 67% were free of this invasion (16/24, PNI-negative group). All PNI-positive cats developed local recurrence, whereas only five PNI-negative cats experienced recurrence. Local recurrence was significantly associated with PNI (p = 0.03). The results of this study are preliminary but promising. The data obtained are the first regarding PNI occurrence in feline SCC and pave the way for further studies, mainly to correlate the PNI with survival data and better define its prognostic value.

Electrochemotherapy (ECT) in treatment of mucosal head and neck tumors. An international network for sharing practices on ECT (InspECT) study group report

The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck.A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe.Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent.This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent.

Treatment of vulvar cancer recurrence with electrochemotherapy: a case-control study.

Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue. The aim of the study was to compare the ECT treatment of vulvar cancer recurrence for non-palliative purposes with surgical treatment. Eleven patients with single vulvar cancer recurrence were treated with ECT and followed up for 12 months. As a control group, 15 patients with single vulvar cancer recurrence were treated with wide local excision. The following data were collected, analyzed and compared: Age, body mass index, comorbidities, histological type, location and size of vulvar cancer recurrence, treatment history, details of procedures and hospital stay. The probability curves for local tumor control did not differ between the ECT group and the surgical group (p = 0.694). The mean hospital stay and the mean duration of procedure were statistically significantly shorter in the ECT group (p < 0.001). There were no statistically significant differences between the ECT and surgical groups in terms of mean body mass index, associated diseases, previous treatments, presence of lichen sclerosus, p16 status, gradus, anatomical site of the tumor, and type of anesthesia. In this case-control study, treatment of vulvar cancer recurrence with ECT for non-palliative purposes was comparable to surgical treatment in terms of effectiveness. The results need to be confirmed in larger randomized trials.

The Efficacy of Electrochemotherapy with Dacarbazine on Melanoma Cells.

Electrochemotherapy (ECT) involves locally applying electrical pulses to permeabilize cell membranes, using electroporation (EP). This process enhances the uptake of low-permeant chemotherapeutic agents, consequently amplifying their cytotoxic effects. In melanoma treatment, dacarbazine (DTIC) is a cornerstone, but it faces limitations because of poor cell membrane penetration, necessitating the use of high doses, which, in turn, leads to increased side effects. In our study, we investigated the effects of DTIC and EP, both individually and in combination, on the melanoma cell line (SK-MEL-30) as well as human dermal fibroblasts (HDF) using in vitro assays. First, the effects of different DTIC concentrations on the viability of SK-MEL-30 and HDF cells were determined, revealing that DTIC was more effective against melanoma cells at lower concentrations, whereas its cytotoxicity at 1000 μM was similar in both cell types. Next, an ideal electric field strength of 1500 V/cm achieved a balance between permeability (84%) and melanoma cell viability (79%), paving the way for effective ECT. The combined DTIC-EP (ECT) application reduced IC50 values by 2.2-fold in SK-MEL-30 cells and 2.7-fold in HDF cells compared with DTIC alone. In conclusion, ECT not only increased DTIC's cytotoxicity against melanoma cells but also affected healthy fibroblasts. These findings emphasize the need for cautious, targeted ECT management in melanoma therapy.

Electrochemotherapy in Kaposi's Sarcoma Patients: From the Gold Standard Strategy to Locally Advanced Cutaneous and Subcutaneous Lesions.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions.

Electroporation in Translational Medicine: From Veterinary Experience to Human Oncology.

Electroporation (EP) is a broadly accepted procedure that, through the application of electric pulses with appropriate amplitudes and waveforms, promotes the delivery of anticancer molecules in various oncology therapies. EP considerably boosts the absorptivity of targeted cells to anticancer molecules of different natures, thus upgrading their effectiveness. Its use in veterinary oncology has been widely explored, and some applications, such as electrochemotherapy (ECT), are currently approved as first-line treatments for several neoplastic conditions. Other applications include irreversible electroporation and EP-based cancer vaccines. In human oncology, EP is still mostly restricted to therapies for cutaneous tumors and the palliation of cutaneous and visceral metastases of malignant tumors. Fields where veterinary experience could help smooth the clinical transition to humans include intraoperative EP, interventional medicine and cancer vaccines. This article recapitulates the state of the art of EP in veterinary and human oncology, recounting the most relevant results to date.

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin - an in vitro study.

Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT. We performed in vitro experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay. We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2-7 × 107 per cell. High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.

Electrochemotherapy for head and neck cancers: possibilities and limitations.

Head and neck cancer continues to be among the most prevalent types of cancer globally, yet it can be managed with appropriate treatment approaches. Presently, chemotherapy and radiotherapy stand as the primary treatment modalities for various groups and regions affected by head and neck cancer. Nonetheless, these treatments are linked to adverse side effects in patients. Moreover, due to tumor resistance to multiple drugs (both intrinsic and extrinsic) and radiotherapy, along with numerous other factors, recurrences or metastases often occur. Electrochemotherapy (ECT) emerges as a clinically proven alternative that offers high efficacy, localized effect, and diminished negative factors. Electrochemotherapy involves the treatment of solid tumors by combining a non-permeable cytotoxic drug, such as bleomycin, with a locally administered pulsed electric field (PEF). It is crucial to employ this method effectively by utilizing optimal PEF protocols and drugs at concentrations that do not possess inherent cytotoxic properties. This review emphasizes an examination of diverse clinical practices of ECT concerning head and neck cancer. It specifically delves into the treatment procedure, the choice of anti-cancer drugs, pre-treatment planning, PEF protocols, and electroporation electrodes as well as the efficacy of tumor response to the treatment and encountered obstacles. We have also highlighted the significance of assessing the spatial electric field distribution in both tumor and adjacent tissues prior to treatment as it plays a pivotal role in determining treatment success. Finally, we compare the ECT methodology to conventional treatments to highlight the potential for improvement and to facilitate popularization of the technique in the area of head and neck cancers where it is not widespread yet while it is not thecase with other cancer types.

Post-Irradiation Breast Angiosarcoma: All the Possible Treatments and Electrochemotherapy. Case Report and Literature Review.

Breast angiosarcoma is a rare malignancy, accounting for less than 1% of all soft tissue cancers. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite multimodal treatment, angiosarcomas represent an incurable disease for many patients and a significant cause of deterioration in their quality of life. Surgery is a cornerstone in management, but high recurrence rates are reported. Electrochemotherapy (ECT) is a practicable locoregional treatment for patients with advanced angiosarcoma as part of a multimodal therapeutic strategy. The palliative benefits of ECT include optimal patient compliance, good local hemostasis control, and positive local responses. Since only 22 cases are described in the literature, we reported a rare case of RAS treated with ECT after a multidisciplinary approach, including Next Generation Sequencing (NGS). A literature review on the feasibility of ECT in RAS management was also performed.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.

Surgical Bedside Electrochemotherapy for Local Control of a Recurrent Phylloid Malignant Breast Tumor: A Case Report.

We present the case of a recurrent malignant phyllodes tumor of the breast, after mastectomy and radiotherapy, in which electrochemotherapy (ECT) was applied to the tumor bed, to achieve better local control. A 66-year-old woman with a large malignant phyllodes tumor of the right breast with a size of 40 cm underwent right radical mastectomy and right axillary lymph node sampling. One month after surgery, with histologically clear margins, the woman presented with multiple small oval masses in the upper portion of the chest wall, indicating rapid disease progression. A second radical excision with clear margins was performed, followed by adjuvant radiotherapy. Two months after the end of treatment, a new 3-cm mass was present in the right axillary extension. The patient underwent a third extensive debulking surgery. At the end of the resection, ECT was applied on the tumor bed along the extensive skin flaps and resection margins. After eight months of follow-up, breast magnetic resonance imaging and total body computed tomography showed disease recurrence in the anterior portion of the right serratus muscle and in the lungs bilaterally. The area undergoing previous ECT showed no disease recurrence. The patient received two lines of palliative chemotherapy. She died 28 months after diagnosis. At the time of death, the large area treated with ECT was geometrically spared from local disease progression. This case report suggests the potential efficacy of ECT at the operating bedside to increase local control in aggressive malignancies.