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Damijan Miklavčič - One of the best experts on this subject based on the ideXlab platform.
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Electrochemotherapy as treatment option for hepatocellular carcinoma a prospective pilot study
Ejso, 2018Co-Authors: Mihajlo Djokic, Bor Kos, Maja Cemazar, Damijan Miklavčič, Peter Popovic, Rok Dezman, Masa Bosnjak, Martina Niksic Zakelj, Stojan Potrc, Borut StabucAbstract:Abstract Background and objectives Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of Electrochemotherapy. Patients and methods Electrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months. Results Electrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8–41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3–6 months was 80% per patient and 88% per treated lesion. Conclusions Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality.
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Electrochemotherapy by pulsed electromagnetic field treatment pemf in mouse melanoma b16f10 in vivo
Radiology and Oncology, 2016Co-Authors: Simona Kranjc, Gregor Sersa, Matej Kranjc, Janez Scancar, Jure Jelenc, Damijan MiklavčičAbstract:Introduction: Pulsed electromagnetic field (PEMF) induces pulsed electric field, which increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Materials and methods: Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intravenously injection of CDDP (4 mg/kg), PEMF (480 bipolar pulses, at frequency of 80 Hz, pulse duration of 340 µs) or with the combination of both therapies (Electrochemotherapy – PEMF + CDDP). Antitumor effectiveness of treatments was evaluated by tumor growth delay assay. In addition, the Pt uptake in tumors and serum, as well as Pt bound to the DNA in the cells and Pt in the extracellular fraction were measured by inductively coupled plasma mass spectrometry. Results: The antitumor effectiveness of Electrochemotherapy with CDDP mediated by PEMF was comparable to the conventional Electrochemotherapy with CDDP, with the induction of 2.3 days and 3.0 days tumor growth delay, respectively. The exposure of tumors to PEMF only, had no effect on tumor growh, as well as the injection of CDDP only. The effect of the combined treatment was due to the increased cellular uptake of Pt in the tumors after the PEMF exposure, as well as its binding to DNA, as cellular target of CDDP. Approximately 2-fold increase in cellular uptake of Pt was measured. Conclucion: The obtained results on mouse melanoma model in vivo demonstrate the possible use of PEMF induced electroporation for biomedical applications, such as Electrochemotherapy. The main advantages of electroporation mediated by PEMF are contactless and painless application, as well as effective electroporation compared to conventional electroporation.
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recommendations for improving the quality of reporting clinical Electrochemotherapy studies based on qualitative systematic review
Radiation Oncology, 2016Co-Authors: Luca Giovanni Campana, Marko Snoj, Maja Cemazar, Pietro Quaglino, Christian Kunte, Julie Gehl, Sara Valpione, Carlo Riccardo Rossi, A J P Clover, Damijan MiklavčičAbstract:Background Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on Electrochemotherapy. Methods The quality of reporting in published studies on Electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. Results A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on Electrochemotherapy were prepared and summarized into a checklist. Conclusions There is an increasing body of published clinical data on Electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on Electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice.
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Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer
Cancer Immunology Immunotherapy, 2015Co-Authors: Gregor Sersa, Maja Cemazar, Justin Teissié, Emanuela Signori, Urska Kamensek, Guillermo Marshall, Damijan MiklavčičAbstract:Electroporation is a platform technology for drug and gene delivery. When applied to cell in vitro or tissues in vivo, it leads to an increase in membrane permeability for molecules which otherwise cannot enter the cell (e.g., siRNA, plasmid DNA, and some chemotherapeutic drugs). The therapeutic effectiveness of delivered chemotherapeutics or nucleic acids depends greatly on their successful and efficient delivery to the target tissue. Therefore, the understanding of different principles of drug and gene delivery is necessary and needs to be taken into account according to the specificity of their delivery to tumors and/or normal tissues. Based on the current knowledge, Electrochemotherapy (a combination of drug and electric pulses) is used for tumor treatment and has shown great potential. Its local effectiveness is up to 80 % of local tumor control, however, without noticeable effect on metastases. In an attempt to increase systemic antitumor effectiveness of Electrochemotherapy, electrotransfer of genes with immunomodulatory effect (immunogene electrotransfer) could be used as adjuvant treatment. Since Electrochemotherapy can induce immunogenic cell death, adjuvant immunogene electrotransfer to peritumoral tissue could lead to locoregional effect as well as the abscopal effect on distant untreated metastases. Therefore, we propose a combination of Electrochemotherapy with peritumoral IL-12 electrotransfer, as a proof of principle, using Electrochemotherapy boosted with immunogene electrotransfer as in situ vaccination for successful tumor treatment.
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coupling treatment planning with navigation system a new technological approach in treatment of head and neck tumors by Electrochemotherapy
Biomedical Engineering Online, 2015Co-Authors: Ales Groselj, Bor Kos, Maja Cemazar, Damijan Miklavčič, Masa Bosnjak, Primoz Strojan, Jure Urbancic, Grega Kragelj, Biserka Veberic, Gregor SersaAbstract:Electrochemotherapy provides highly effective local treatment for a variety of tumors. In deep-seated tumors of the head and neck, due to complex anatomy of the region or inability to cover the whole tumor with standard electrodes, the use of long single needle electrodes is mandatory. In such cases, a treatment plan provides the information on the optimal configuration of the electrodes to adequately cover the tumor with electric field, while the accurate placement of the electrodes in the surgical room in patients can remain a problem. Therefore, during Electrochemotherapy of two head and neck lymph-node metastases of squamous cell carcinoma origin, a navigation system for placement of electrodes was used. Electrochemotherapy of two lymph-node metastases of cutaneous squamous cell carcinoma, one in the left parotid gland and the other in the neck just behind the left mandibular angle, was performed using intravenous administration of bleomycin and long single needle electrodes. The tumors were treated according to the prepared treatment plan, and executed with the use of navigation system. Coupling of treatment plan with the navigation system aided to an accurate placement of the electrodes. The navigation system helped the surgeon to identify the exact location of the tumors, and helped with the positioning of the long needle electrodes during their insertion, according to treatment plan. Five electrodes were inserted for each metastasis, one centrally in the tumor and four in the periphery of the tumor. Five weeks after Electrochemotherapy, computed tomography images demonstrated partial response of the first metastasis and complete response of the second one. Six weeks after Electrochemotherapy, fine-needle aspiration biopsy specimen obtained from the treated lesions revealed necrosis and inflammatory cells, without any viable tumor cells. We describe a new technological approach for Electrochemotherapy of deep-seated head and neck tumors, coupling of the treatment planning with navigation system for accurate placement of the single long needle electrodes into and around the tumors, according to the treatment plan. Evidence of its effectiveness on two lymph-node metastases of cutaneous squamous cell carcinoma origin in neck lymph is provided.
Gregor Sersa - One of the best experts on this subject based on the ideXlab platform.
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Large Liver Blood Vessels and Bile Ducts Are Not Damaged by Electrochemotherapy with Bleomycin in Pigs
Scientific Reports, 2019Co-Authors: Jan Zmuc, Gregor Sersa, Ibrahim Edhemovic, Erik Brecelj, Gorana Gasljevic, Alenka Seliskar, Tanja Plavec, Maja Brloznik, Nina Milevoj, Jani IzlakarAbstract:The first clinical studies on the use of Electrochemotherapy to treat liver tumours that were not amenable to surgery or thermal ablation techniques have recently been published. However, there is still a lack of data on the effects of Electrochemotherapy on normal liver tissue. Therefore, we designed a translational animal model study to test whether Electrochemotherapy with bleomycin causes clinically significant damage to normal liver tissue, with emphasis on large blood vessels and bile ducts. We performed Electrochemotherapy with bleomycin or delivered electric pulses alone using a potentially risky treatment strategy in eight pigs. Two and seven days after treatment, livers were explanted, and histological analysis was performed. Blood samples were collected before treatment and again before euthanasia to evaluate blood biomarkers of liver function and systemic inflammatory response. We found no thrombosis or other clinically significant damage to large blood vessels and bile ducts in the liver. No clinical or laboratory findings suggested impaired liver function or systemic inflammatory response. Electrochemotherapy with bleomycin does not cause clinically significant damage to normal liver tissue. Our study provides further evidence that Electrochemotherapy with bleomycin is safe for treatment of patients with tumours near large blood vessels in the liver.
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updated standard operating procedures for Electrochemotherapy of cutaneous tumours and skin metastases
Acta Oncologica, 2018Co-Authors: Julie Gehl, Declan M Soden, Gregor Sersa, Pietro Quaglino, Louise Wichmann Matthiessen, Pietro Curatolo, Tobian Muir, Luca Giovanni Campana, Antonio Occhini, Christian KunteAbstract:Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for Electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.
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histopathological findings in colorectal liver metastases after Electrochemotherapy
PLOS ONE, 2017Co-Authors: Gorana Gasljevic, Maja Cemazar, Ibrahim Edhemovic, Erik Brecelj, Maja Marolt Music, Eldar M Gadzijev, Gregor SersaAbstract:Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in Electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8-10 weeks) in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8-10 weeks after Electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole Electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by Electrochemotherapy is provided. These findings are important because Electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy.
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efficacy and safety of Electrochemotherapy combined with peritumoral il 12 gene electrotransfer of canine mast cell tumours
Veterinary and Comparative Oncology, 2017Co-Authors: Maja Cemazar, Gregor Sersa, Ambrozic J Avgustin, Darja Pavlin, Alessandro Poli, Krhac A Levacic, Natasa Tesic, Lampreht U Tratar, Mitja Rak, Natasa TozonAbstract:Electrochemotherapy combined with peritumoral interleukin-12 (IL-12) gene electrotransfer was used for treatment of mast cell tumours in 18 client-owned dogs. Local tumour control, recurrence rate, as well as safety of combined therapy were evaluated. One month after the therapy, no side effects were recorded and good local tumour control was observed with high complete responses rate which even increased during the observation period to 72%. IL-12 gene electrotransfer resulted in 78% of patients with detectable serum IFN-γ and/or IL-12 levels. In the treated tumours vascular changes as well as minimal T-lymphocytes infiltration was observed. After 1 week, the plasmid DNA was not detected intra- or peritumorally and no horizontal gene transfer was observed. In summary, our study demonstrates high antitumour efficacy of Electrochemotherapy combined with IL-12 electrotransfer, which also prevented recurrences or distant metastases, as well as its safety and feasibility in treatment of canine mast cell tumours.
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european research on Electrochemotherapy in head and neck cancer eureca project results from the treatment of mucosal cancers
European Journal of Cancer, 2016Co-Authors: Christina Caroline Plaschke, Gregor Sersa, Giulia Bertino, J Mccaul, Juan J Grau, Remco De Bree, Antonio Occhini, Ales Groselj, Cristobal LangdonAbstract:Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of Electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for Electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427).
Maja Cemazar - One of the best experts on this subject based on the ideXlab platform.
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Electrochemotherapy as treatment option for hepatocellular carcinoma a prospective pilot study
Ejso, 2018Co-Authors: Mihajlo Djokic, Bor Kos, Maja Cemazar, Damijan Miklavčič, Peter Popovic, Rok Dezman, Masa Bosnjak, Martina Niksic Zakelj, Stojan Potrc, Borut StabucAbstract:Abstract Background and objectives Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of Electrochemotherapy. Patients and methods Electrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months. Results Electrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8–41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3–6 months was 80% per patient and 88% per treated lesion. Conclusions Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality.
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histopathological findings in colorectal liver metastases after Electrochemotherapy
PLOS ONE, 2017Co-Authors: Gorana Gasljevic, Maja Cemazar, Ibrahim Edhemovic, Erik Brecelj, Maja Marolt Music, Eldar M Gadzijev, Gregor SersaAbstract:Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in Electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8-10 weeks) in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8-10 weeks after Electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole Electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by Electrochemotherapy is provided. These findings are important because Electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy.
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efficacy and safety of Electrochemotherapy combined with peritumoral il 12 gene electrotransfer of canine mast cell tumours
Veterinary and Comparative Oncology, 2017Co-Authors: Maja Cemazar, Gregor Sersa, Ambrozic J Avgustin, Darja Pavlin, Alessandro Poli, Krhac A Levacic, Natasa Tesic, Lampreht U Tratar, Mitja Rak, Natasa TozonAbstract:Electrochemotherapy combined with peritumoral interleukin-12 (IL-12) gene electrotransfer was used for treatment of mast cell tumours in 18 client-owned dogs. Local tumour control, recurrence rate, as well as safety of combined therapy were evaluated. One month after the therapy, no side effects were recorded and good local tumour control was observed with high complete responses rate which even increased during the observation period to 72%. IL-12 gene electrotransfer resulted in 78% of patients with detectable serum IFN-γ and/or IL-12 levels. In the treated tumours vascular changes as well as minimal T-lymphocytes infiltration was observed. After 1 week, the plasmid DNA was not detected intra- or peritumorally and no horizontal gene transfer was observed. In summary, our study demonstrates high antitumour efficacy of Electrochemotherapy combined with IL-12 electrotransfer, which also prevented recurrences or distant metastases, as well as its safety and feasibility in treatment of canine mast cell tumours.
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bleomycin pharmacokinetics of bolus bleomycin dose in elderly cancer patients treated with Electrochemotherapy
Cancer Chemotherapy and Pharmacology, 2016Co-Authors: Ales Groselj, Gregor Sersa, Maja Cemazar, Mojca Krzan, Tina Kosjek, M BosnjakAbstract:With the aim to determine effective therapeutic window of Electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients. In prospective clinical study in the treatment of tumors with Electrochemotherapy, blood samples of patients older than 65 years were collected after the bolus intravenous injection of bleomycin (15,000 IU/m2). In serum samples, quantitative analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. Based on the data, the pharmacokinetic parameters of bleomycin elimination were determined. Pharmacokinetic analysis of the data revealed a monophasic serum clearance curve, which demonstrates slow elimination of bleomycin, being less than 500 ml/min and a half-time of 30 min. Slow monophasic elimination of bleomycin from serum in elderly patients implies on the longer therapeutic window, from 8 to up to 40 min or even longer post-bleomycin injection for Electrochemotherapy. However, prolonged therapeutic bleomycin serum concentrations may also affect the possible adverse effects, such as lung fibrosis and extensive necrosis of tumors due to the uptake of toxic bleomycin concentrations into the tumors. This may imply on lowering of bleomycin dosage, in particular in the elderly patients.
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Electrochemotherapy in veterinary medicine our clinical experiences
2016Co-Authors: Natasa Tozon, Gregor Sersa, Maja CemazarAbstract:Electrochemotherapy (ECT) is combined local or systemic chemotherapy with electroporation that permeabilize cell membranes to locally potentiate the antitumor effectiveness of chemotherapeutic drugs. ECT became a standard method for the specific type and location of tumors (cutaneous, subcutaneous and oral tumors) in dogs, cats and horses. It can be used as a single therapy or as an adjuvant therapy to surgery. The results of the clinical trials conducted at the Clinic for surgery and small animals of Veterinary Faculty in collaboration with the Institute of Oncology Ljubljana are presented.
Julie Gehl - One of the best experts on this subject based on the ideXlab platform.
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Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin analysis of 57 patients from the international network for sharing practices of Electrochemotherapy registry
Journal of The European Academy of Dermatology and Venereology, 2018Co-Authors: Roberta Rotunno, Pietro Quaglino, Christian Kunte, J Odili, S H Liew, Julie Gehl, Luca Giovanni Campana, F De Terlizzi, Simone Ribero, Roberto MarconatoAbstract:Background Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. Objective The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. Methods In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 , instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. Results We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). Conclusions Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.
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updated standard operating procedures for Electrochemotherapy of cutaneous tumours and skin metastases
Acta Oncologica, 2018Co-Authors: Julie Gehl, Declan M Soden, Gregor Sersa, Pietro Quaglino, Louise Wichmann Matthiessen, Pietro Curatolo, Tobian Muir, Luca Giovanni Campana, Antonio Occhini, Christian KunteAbstract:Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for Electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.
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calcium electroporation for treatment of cutaneous metastases a randomized double blinded phase ii study comparing the effect of calcium electroporation with Electrochemotherapy
Acta Oncologica, 2017Co-Authors: Hanne Falk, Louise Wichmann Matthiessen, Gitte Wooler, Julie GehlAbstract:AbstractBackground: Calcium electroporation is a novel anticancer treatment, which utilizes high voltage pulses to permeabilize cell membranes and expose the cell to supraphysiological doses of calcium. Preclinical studies on calcium electroporation have shown strikingly high tumor response with cell necrosis. Calcium electroporation builds on the treatment Electrochemotherapy, where chemotherapeutic drugs, mostly bleomycin, are internalized by electroporation. This double-blinded randomized study compared calcium electroporation to Electrochemotherapy in terms of objective response measured 6 months after treatment.Methods: Seven patients with a total of 47 cutaneous metastases from breast cancer and malignant melanoma were included in the protocol. A total of 37 metastases were randomized and evaluated for response, another 10 metastases were used for biopsy. This was a non-inferiority trial and metastases were randomized individually in each patient to either intratumoral calcium or bleomycin followed ...
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Electrochemotherapy and calcium electroporation inducing a systemic immune response with local and distant remission of tumors in a patient with malignant melanoma a case report
Acta Oncologica, 2017Co-Authors: Hanne Falk, Helle Hjorth Johannesen, Susanne Lambaa, Gitte Wooler, Alessandro Venzo, Julie GehlAbstract:In this case study, we report a remarkable systemic response after treatment with Electrochemotherapy and calcium electroporation in a patient with disseminated malignant melanoma.Electrochemothera...
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recommendations for improving the quality of reporting clinical Electrochemotherapy studies based on qualitative systematic review
Radiation Oncology, 2016Co-Authors: Luca Giovanni Campana, Marko Snoj, Maja Cemazar, Pietro Quaglino, Christian Kunte, Julie Gehl, Sara Valpione, Carlo Riccardo Rossi, A J P Clover, Damijan MiklavčičAbstract:Background Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on Electrochemotherapy. Methods The quality of reporting in published studies on Electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. Results A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on Electrochemotherapy were prepared and summarized into a checklist. Conclusions There is an increasing body of published clinical data on Electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on Electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice.
Luca Giovanni Campana - One of the best experts on this subject based on the ideXlab platform.
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Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin analysis of 57 patients from the international network for sharing practices of Electrochemotherapy registry
Journal of The European Academy of Dermatology and Venereology, 2018Co-Authors: Roberta Rotunno, Pietro Quaglino, Christian Kunte, J Odili, S H Liew, Julie Gehl, Luca Giovanni Campana, F De Terlizzi, Simone Ribero, Roberto MarconatoAbstract:Background Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. Objective The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. Methods In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 , instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. Results We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). Conclusions Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.
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updated standard operating procedures for Electrochemotherapy of cutaneous tumours and skin metastases
Acta Oncologica, 2018Co-Authors: Julie Gehl, Declan M Soden, Gregor Sersa, Pietro Quaglino, Louise Wichmann Matthiessen, Pietro Curatolo, Tobian Muir, Luca Giovanni Campana, Antonio Occhini, Christian KunteAbstract:Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for Electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.
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local treatment with Electrochemotherapy of superficial angiosarcomas efficacy and safety results from a multi institutional retrospective study
Journal of Surgical Oncology, 2016Co-Authors: M Guida, Pietro Curatolo, Roberta Rotunno, Luca Giovanni Campana, Sabino Strippoli, Antonio Bonadies, Gretha Grilz, Carlo Cabula, Stefania Bucher, Nicola SolariAbstract:Background Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. Methods This multicenter retrospective analysis reviewed patients who underwent Electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. Results Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n = 5), breast (n = 8), other skin sites (n = 3), and soft tissue (n = 3). Target lesions (n = 54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). Conclusions Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas. J. Surg. Oncol. 2016;114:246–253. © 2016 Wiley Periodicals, Inc.
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recommendations for improving the quality of reporting clinical Electrochemotherapy studies based on qualitative systematic review
Radiation Oncology, 2016Co-Authors: Luca Giovanni Campana, Marko Snoj, Maja Cemazar, Pietro Quaglino, Christian Kunte, Julie Gehl, Sara Valpione, Carlo Riccardo Rossi, A J P Clover, Damijan MiklavčičAbstract:Background Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on Electrochemotherapy. Methods The quality of reporting in published studies on Electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. Results A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on Electrochemotherapy were prepared and summarized into a checklist. Conclusions There is an increasing body of published clinical data on Electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on Electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice.
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Electrochemotherapy in the treatment of cutaneous metastases from breast cancer a multicenter cohort analysis
Annals of Surgical Oncology, 2015Co-Authors: Carlo Cabula, Pietro Curatolo, Luca Giovanni Campana, Antonio Bonadies, Gretha Grilz, Sara Galuppo, Riccardo Bussone, L De Meo, M De Laurentiis, M RenneAbstract:Background The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging.