Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study

Marty, M.; Serša, Gregor; Garbay, Jean Rémi; Gehl, Julie; Collins, Christopher G.; Snoj, Marko; Billard, V.; Geertsen, Poul F.; Larkin, John; Miklavčič, Damijan; Pavlović, Ivan; Paulin-Kosir, Snezna M.; Čemažar, Maja; Morsli, Nassim; Soden, Declan M.; Rudolf, Z; Robert, Caroline; O’Sullivan, Gerald C.; Mir, Lluis M.

doi:10.1016/j.ejcsup.2006.08.002

Cited by 798 publications

(855 citation statements)

References 24 publications

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“…All the lesions treated were smaller than 3 cm in diameter. Bleomycin was administered intravenously (15,000 UI/m 2 body surface area) in a time frame of 60 s. The electrical pulses (variable amplitude with 1-5,000 Hz delivery frequencies) were applied to the metastasis in a time window between 8 and 28 min after bleomycin infusion to obtain the optimal response utilizing the most appropriate drug concentrations in tissues, according to previous standardized procedure [1,4].…”

Section: Patients and Human Tissuesmentioning

confidence: 99%

“…Electrochemotherapy (ECT) is emerging as a highly effective local treatment for skin metastasis of human cancers and it is particularly used for recurrent or in-transit unresectable melanoma metastases [1,2]. ECT treatment is based on the administration of anti-neoplastic drugs, such as bleomycin or cisplatin, followed by the electroporation of the lesions [3].…”

Section: Introductionmentioning

confidence: 99%

“…The electric currents, increasing cell membrane permeability, promote the intracellular concentration of the drug and increase its cytotoxicity [4]. Although the overall objective response rate is high, approximately 80-90 % [1], it is generally accepted that ECT has only local effects, therefore it is currently used as a palliative treatment. However, some findings support the view that ECT can also induce anticancer immunity, especially in melanoma which is considered the most immunogenic tumours [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy

Gerlini

Sestini

Gennaro

et al. 2012

Clin Exp Metastasis

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Section: Patients and Human Tissuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy

Gerlini

Sestini

Gennaro

et al. 2012

Clin Exp Metastasis

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“…ECT is already used in clinical practice for treating metastases of skin melanoma in more than 100 clinical institutions in Europe ) and has already been introduced to clinical trials for treating deep-seated metastases in the liver (Edhemović et al 2011), brain (AgerholmLarsen et al 2011;Linnert et al 2012;Mahmood and Gehl 2011), bone (Fini et al 2011) and soft tissue (Neal et al 2011). While following standard operating procedures (Mir et al 2006) ensures safe and successful treatment of skin melanoma metastases (Marty et al 2006), patient-specific treatment planning is nevertheless required for ECT of deep-seated tumors (Pavliha et al 2012). Namely, deepseated tumors are very diverse in shape, size and location in the body; and long-needle electrodes are used for treating such tumors; therefore, coverage of the whole target tissue (i.e., tumor) with a sufficiently high electric field (which is a prerequisite for successful ECT) (Miklavčič et al 1998(Miklavčič et al , 2006 can currently only be assured by means of numerical modeling of electric field distribution.…”

Section: Introductionmentioning

confidence: 99%

Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software

et al. 2013

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Electroporation-based treatment combining high-voltage electric pulses and poorly permanent cytotoxic drugs, i.e., electrochemotherapy (ECT), is currently used for treating superficial tumor nodules by following standard operating procedures. Besides ECT, another electroporation-based treatment, nonthermal irreversible electroporation (N-TIRE), is also efficient at ablating deepseated tumors. To perform ECT or N-TIRE of deep-seated tumors, following standard operating procedures is not sufficient and patient-specific treatment planning is required for successful treatment. Treatment planning is required because of the use of individual long-needle electrodes and the diverse shape, size and location of deepseated tumors. Many institutions that already perform ECT of superficial metastases could benefit from treatmentplanning software that would enable the preparation of patient-specific treatment plans. To this end, we have developed a Web-based treatment-planning software for planning electroporation-based treatments that does not require prior engineering knowledge from the user (e.g., the clinician). The software includes algorithms for automatic tissue segmentation and, after segmentation, generation of a 3D model of the tissue. The procedure allows the user to define how the electrodes will be inserted. Finally, electric field distribution is computed, the position of electrodes and the voltage to be applied are optimized using the 3D model and a downloadable treatment plan is made available to the user.

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“…Bleomycin (BLM) and cisplatin proved to be effective in electrochemotherapy for treatment of various tumours in mice, rats, cats, dogs and horses (Sersa et al, 2006b). In a clinical setting, several studies predominantly on patients with malignant melanoma, basal cell carcinoma, head and neck tumours, and others have proved antitumour effectiveness of electrochemotherapy by long-lasting local tumour control (Heller et al, 1999;Marty et al, 2006;Sersa, 2006a).…”

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confidence: 99%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1 mg kg À1 ), application of electric pulses (8 pulses, 1040 V, 100 ms, 1 Hz) or a combination of both -electrochemotherapy. The vascular effect was determined by laser Doppler flowmetry, power Doppler ultrasonographic imaging and Patent blue staining. The extent of tumour hypoxia was determined immunohistochemically by hypoxia marker pimonidazole and partial pressure of oxygen (pO 2 ) in tumours by electron paramagnetic resonance oximetry. Electrochemotherapy with BLM induced good antitumour effect with 22 days, tumour growth delay and 38% tumour cures. The application of electric pulses to the tumours induced instant but transient tumour blood flow reduction (for 70%) that was recovered in 24 h. During this tumour blood flow reduction, we determined an increase in hypoxic tumour area for up to 30%, which was also reflected in reduced tumour oxygenation (for 70%). According to the described mathematical model, endothelial cells lining in tumour blood vessels are exposed to a B40% higher electric field than the surrounding tumour cells, and therefore easily electroporated, allowing access of high BLM concentration to the cytosol. Consequently, electrochemotherapy has, besides the immediate vascular disrupting action, also a delayed one (after 24 h), as a consequence of endothelial cell swelling and apoptosis demonstrated by extensive tumour necrosis, tumour hypoxia, prolonged reduction of tumour blood flow and significant tumour growth delay, and tumour cures. Our results demonstrate that in addition to the well-established direct cytotoxic effect on tumour cells, electrochemotherapy also has an indirect vascular disrupting action resulting altogether in extensive tumour cell necrosis leading to complete regression of tumours.

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Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study

Cited by 798 publications

References 24 publications

Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy

Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy

Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

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