Bleomycin-based Electrochemotherapy Research Articles

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.

Current Updates in Bleomycin-Based Electrochemotherapy for Deep-Seated Soft-Tissue Tumors

Electrochemotherapy (ECT) has evolved significantly during the last decade, expanding treatment indications from superficial skin lesions to advanced-stage, deep-seated tumors in hard-to-reach areas. Electrodes have also shown steady technological improvement throughout the years. Besides standard and VEG (variable geometry electrode) electrodes, the introduction of laparoscopic electrodes has brought on a new era in ECT treatment, making the minimally invasive approach a reality. The exact role of ECT in the oncological dashboard is yet to be determined; however, increased tumor response, pain relief, and a low number of adverse events may yield the way for more widespread application of the technique with possible further inclusion of ECT in international oncological guidelines. The aim of this review is to give an overview on the current status of ECT in deep-seated tumor treatment and shed light on its emerging role in local anticancer therapy.

Electrochemotherapy in radiotherapy-resistant epidural spinal cord compression in metastatic cancer patients

ObjectiveTo report efficacy and safety of percutaneous electrochemotherapy (ECT) in patients with radiotherapy-resistant metastatic epidural spinal cord compression (MESCC). Material/ methodsThis retrospective study analyzed all consecutive patients treated with bleomycin-based ECT between February-2020 and September-2022 in a single tertiary referral cancer center. Changes in pain were evaluated with the Numerical Rating Score (NRS), in neurological deficit with the Neurological Deficit Scale, and changes in epidural spinal cord compression were evaluated with the epidural spinal cord compression scale (ESCCS) using an MRI. ResultsForty consecutive solid tumour patients with previously radiated MESCC and no effective systemic treatment options were eligible. With a median follow-up of 5.1 months [1–19.1], toxicities were temporary acute radicular pain (25%), prolonged radicular hypoesthesia (10%), and paraplegia (7.5%). At 1 month, pain was significantly improved over baseline (median NRS: 1.0 [0–8] versus 7.0 [1.0–10], P < .001) and neurological benefits were considered as marked (28%), moderate (28%), stable (38%), or worse (8%). Three-month follow-up (21 patients) confirmed improved over baseline (median NRS: 2.0 [0–8] versus 6.0 [1.0–10], P < .001) and neurological benefits were considered as marked (38%), moderate (19%), stable (33.5%), and worse (9.5%). One-month post-treatment MRI (35 patients) demonstrated complete response in 46% of patients by ESCCS, partial response in 31%, stable disease in 23%, and no patients with progressive disease. Three-month post-treatment MRI (21 patients) demonstrated complete response in 28.5%, partial response in 38%, stable disease in 24%, and progressive disease in 9.5%. ConclusionsThis study provides the first evidence that ECT can rescue radiotherapy-resistant MESCC.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients

ObjectiveThe management of vulvar cancer recurrences is complicated by patients’ advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes...

Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma.

Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application. Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured. CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (p-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33-40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days. Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option.

Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial.

Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option.

A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer.

Electrochemotherapy is an efficient method for the local treatment of cutaneous and subcutaneous metastases, but its efficacy as a systemic treatment remains low. The application of gene electrotransfer (GET) to transfer DNA coding for immune system modulating molecules could allow for a systemic effect, but its applications are limited because of possible side effects, e.g., immune system overactivation and autoimmune response. In this paper, we present the simultaneous electrotransfer of bleomycin and plasmid DNA as a method to increase the systemic effect of bleomycin-based electrochemotherapy. With appropriately selected concentrations of bleomycin and plasmid DNA, it is possible to achieve efficient cell transfection while killing cells via the cytotoxic effect of bleomycin at later time points. We also show the dynamics of both cell electrotransfection and cell death after the simultaneous electrotransfer of bleomycin and plasmid DNA. Therefore, this method could have applications in achieving the transient, cell death-controlled expression of immune system activating genes while retaining efficient bleomycin mediated cell killing.

Outcomes of Bleomycin-based electrochemotherapy in patients with repeated loco-regional recurrences of vulvar cancer

Objective To evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments.Methods Ten patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires.Results Diagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD ± 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10–20) min. After a median follow-up of 12 (3–22) months, six patients (60%) were alive.Conclusions Objective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3–22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting.

The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy: a phase-II study

Electrochemotherapy (ECT) represents an attractive locoregional therapy for unresectable chest wall recurrence (CWR) from breast cancer. Thirty-five patients with cutaneous CWR after mastectomy who experienced progression despite re-irradiation and extensive systemic treatments were administered bleomycin-based ECT. Local response, toxicity, and superficial control were evaluated. Out of 516 metastases (median 15/patient, range 1-50), response was assessed on 196 target lesions (median size 20 mm, range 10-220). Patients received a median of 2 ECT courses (range 1-3). Two-month objective response was as follows: 54.3 % complete (19/35 patients), 37.1 % partial (13/35), and 8.6 % no change (3/35). Twenty-three patients (65.7 %) developed new lesions (NL) after a median time of 6.6 months (range 2.3-29.5), therefore 1, 2, or 3 ECT cycles were required in 14, 15, and 6 patients, respectively. Median follow-up was 32 months (range 6-53) and the 3-year local control rate was 81 %. Related morbidity was mild, increased after retreatments and consisted primarily of pain (reported as "moderate"/"severe" by 6, 13, and 17 % of patients 1 month after the first, second, and third application, respectively) and dermatological toxicity (acute G3 skin ulceration in 14, 20, and 33 % of patients, respectively). Less than 10 metastases (P < 0.001), the narrower area of tumor spread on the chest wall (P = 0.022), complete response achievement (P = 0.019), and post-ECT endocrine instead of chemotherapy (P = 0.025) were associated to NL-free survival. Only fewer skin metastases, hazard ratio (HR) 0.122, 95 % confidence interval (CI) 0.037-0.397, P < 0.001, and contained superficial spread, HR 0.234, 95 % CI 0.067-0.818, P = 0.023, were predictors for longer NL-free survival. ECT showed a satisfactory activity in refractory breast cancer CWR, providing sustained local control. Patients with fewer and less scattered skin metastases are less likely to develop NL. Partial responders and NL can be handled with additional ECT albeit increasing local pain and skin toxicity.

Electrochemotherapy for disseminated superficial metastases from malignant melanoma

The aim of the study was to determine predictive factors for effectiveness, toxicity and local disease control in patients with malignant melanoma treated with bleomycin-based electrochemotherapy (ECT). Electrochemotherapy was offered to patients with superficially disseminated melanoma metastases unsuitable for resection and unresponsive to chemotherapy. Eighty-five patients were treated with up to six ECT cycles with minimal, mainly dermatological, toxicity. One month after the first ECT, an objective response was observed in 80 patients (94 per cent). After retreatment because of a partial response in 39 patients, a complete response was achieved in 19 patients. Among the 41 (48 per cent) complete responders at first ECT, 19 patients received a second cycle because of new lesions after a median of 6 (range 2-14) months. After a median follow-up of 26 months, six patients experienced local recurrence with a 2-year local progression-free survival rate of 87 per cent. In multivariable analysis, significant predictive factors for response were tumour size (odds ratio (OR) 0·23, 95 per cent confidence interval (c.i.) 0·19 to 0·86; P = 0·003) and number of lesions (OR 0·38, 0·28 to 0·88; P = 0·002). An increasing number of electrode applications (hazard ratio (HR) 2·18, 95 per cent c.i. 1·22 to 3·44; P = 0·041) and ECT cycles (HR 0·46, 0·22 to 0·95; P = 0·005) were predictors of local control. There were no predictors of toxicity. Melanoma thickness and lower limb location of metastases were prognostic for survival. The most suitable candidates for ECT were patients with few and small metastases on the lower limb treated with multiple electrode applications and ECT cycles.

Successful Treatment of Multiple Basaliomas with Bleomycin-based Electrochemotherapy: A Case Series of Three Patients with Gorlin-Goltz Syndrome

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

9312 POSTER Health-Related Quality of Life Outcomes in Advanced Melanoma Patients After Palliative Treatment With Bleomycin-based Electrochemotherapy

9312 POSTER Health-Related Quality of Life Outcomes in Advanced Melanoma Patients After Palliative Treatment With Bleomycin-based Electrochemotherapy

Bleomycin-Based Electrochemotherapy: Clinical Outcome from a Single Institution’s Experience with 52 Patients

Electrochemotherapy (ECT) has emerged as a complementary treatment for superficial metastases. Fifty-two consecutive patients with different cancer histotypes, mainly melanoma and breast cancer, with disease unsuitable for conventional treatments underwent bleomycin-based ECT for cutaneous and subcutaneous metastases. Toxicity, local response, response duration, and the impact on quality of life were evaluated. A total of 608 tumor nodules were treated (mean, 12 per patient), with 27% of patients affected by nodules >3 cm in size. Treatment was tolerated well, especially under general sedation. An objective response was obtained in 50 (96%) of 52 patients 1 month after the first application. Twenty-two patients underwent a second treatment (because of partial response or the appearance of new lesions). Partial response at first ECT achieved a response consolidation at second application: 80% complete response, 20% partial response. Some patients underwent up to five treatments because of new lesions, but maintained superficial tumor control. After a mean follow-up of 9 (range, 2-21) months, only two patients experienced relapse in the treatment field. Through a nonvalidated eight-item questionnaire (assessing wound healing and bleeding, aesthetic impairment, daily activities, social relations, pain, treatment satisfaction, acceptance of retreatment), most patients reported a benefit in local disease-related complaints and in activity of daily living. In a palliative setting, ECT proved to be safe, effective in all tumors treated, and useful in preserving patients' quality of life. This benefit, although preliminary, deserves further assessment after a formal validation of the dedicated questionnaire.