Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treat... more Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treatment of small superficial lesions. Variable electrode-geometry ECT (VEG-ECT) may overcome these limitations by using long freely-placeable electrodes. Patients with bulky or deep-seated soft-tissue malignancies not amenable to resection participated in a single-arm phase-2 study (ISRCTN.11667954) and received a single course of VEG-ECT with intravenous bleomycin (15,000 IU/m2) and concomitant electric pulses applied through an adjustable electrode array. The primary outcome was radiologic complete response rate (CRR) per RECIST; secondary endpoints included feasibility, metabolic response, toxicity (CTCAE), local progression-free survival (LPFS) and patient perception (EQ-5D). During 2009–2014, we enrolled 30 patients with trunk/limb sarcomas, melanoma, Merkel-cell carcinoma, and colorectal/lung cancer. Median tumour size was 4.7 cm. Electrode probes were placed under US/TC guidance (28 ...
Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, ... more Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, among these, also chest wall recurrences from breast cancer. Generally, the treatment of this peculiar type of tumor requires the coverage of large skin areas. In these cases, electrochemotherapy treatment by means of standard small size needle electrodes (an array of 0.73 cm spaced needles, which covers an area of 1.5 cm) is time-consuming and can allow an inhomogeneous coverage of the target area. We have previously designed grid devices suitable for treating an area ranging from 12 to 200 cm. In this study, we propose different approaches to study advantages and drawbacks of a grid device with needles positioned 2 cm apart. The described approach includes a numerical evaluation to estimate electric field intensity, followed by an experimental quantification of electroporation on a cell culture. The electric field generated in a conductive medium has been studied by means of 3-dimensio...
Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, r... more Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Prim...
Electrochemotherapy (ECT) is an effective local treatment for cutaneous metastasis. Treatment inv... more Electrochemotherapy (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. The aim of this study was to investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors which affect (beneficially or adversely) the outcome. 13 cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoural or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. 151 patients with metastatic melanoma were identified from the database, 114 of which had follow-up data of 60 days or more. 80 of these patients (73%) experienced an overall response (complete response + partial response = OR). 394 lesions were treated, of which 306 (77%) revealed an OR, 229...
Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-ski... more 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. 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...
Journal of experimental & clinical cancer research : CR, 2003
Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patient... more Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical differenc...
Hyperthermic isolation limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) and IFNg... more Hyperthermic isolation limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) and IFNgamma was pioneered by Liénard and Lejeune in 1988. The TNFalpha was empirically employed at a dosage of 3-4 mg, that is ten times the systemic maximum tolerated dose (MTD). After eighteen years from its first clinical application, more than 300 patients have been treated. The aim of this study is to clarify two major arguments: the TNFalpha dose and eligibility criteria for patient selection. A phase I-II study has previously been conducted in 20 patients with in-transit melanoma metastases using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. Twenty patients were treated and a complete pathological response of 70% was recorded, with no correlation between tumor response and TNFalpha. The dose of 1 mg of TNFalpha provided the best results regarding efficacy and toxicity. On the basis of this results a large phase II SITILO study was undertaken. Patients wit...
Background. Peristomal metastases are rare, but potentially associated with relevant morbidity. S... more Background. Peristomal metastases are rare, but potentially associated with relevant morbidity. Surgical resection, followed by stoma relocation, represent the gold standard in most patients. We describe electrochemotherapy (ECT), a minimally invasive method for locally-enhancing drug delivery by means of electric pulses, as an alternative approach. Patient and methods. A 49-year-old man with advanced gastric cancer developed skin metastases around an ileostomy site. The ulcerated and oozing tumor growth impaired patient’s quality of life due to continuous trouble in fitting the ostomy appliance, its poor adherence and consequent stools spillage. ECT consisted of a 20-minute course under mild general sedation. A bleomycin bolus of 15 000 IU/m2 was followed by the percutaneous application of multiple, 1.5 ms -long electric pulses by means of a needle electrode. Results. Post ECT course was uneventful and the patient was discharged on the same day. After one week, tumor nodules were f...
Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating dose... more Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating doses of TNF-alpha (0.5-3.3 mg) and standard doses of doxorubicin (bolus 0.7-1.4 mg/kg) at a tumor temperature of at least 41 degrees C, with the aim to ascertain the maximum tolerable dose (MTD) and the activity of TNF-alpha combined with doxorubicin in hyperthermic antiblastic perfusion (HAP) for patients with limb sarcomas, candidates for amputation. Tumor response was assessed both pathologically and radiologically. Severe systemic toxicity (WHO) was observed in only 2 patients. Locoregional toxicity (Wieberdink's) was grade I in 3 patients, grade II or III in 10 and grade IV in 5. A strict correlation between the TNF dosage and the grade of limb reaction was found, grade IV being retrieved only with TNF dose >1 mg and/or muscular temperature >41.5 degrees C. Tumor necrosis was evaluated in 16 patients: in 11 (68.8%) it scored more than 75% while in 5 it was 25 to 75%. Four cases (25%) had 100% tumor histological necrosis. Limb sparing surgery was feasible in 13 (81%). Our findings suggest that this is a well-tolerated and highly active regimen in HAP.
Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treat... more Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treatment of small superficial lesions. Variable electrode-geometry ECT (VEG-ECT) may overcome these limitations by using long freely-placeable electrodes. Patients with bulky or deep-seated soft-tissue malignancies not amenable to resection participated in a single-arm phase-2 study (ISRCTN.11667954) and received a single course of VEG-ECT with intravenous bleomycin (15,000 IU/m2) and concomitant electric pulses applied through an adjustable electrode array. The primary outcome was radiologic complete response rate (CRR) per RECIST; secondary endpoints included feasibility, metabolic response, toxicity (CTCAE), local progression-free survival (LPFS) and patient perception (EQ-5D). During 2009–2014, we enrolled 30 patients with trunk/limb sarcomas, melanoma, Merkel-cell carcinoma, and colorectal/lung cancer. Median tumour size was 4.7 cm. Electrode probes were placed under US/TC guidance (28 ...
Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, ... more Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, among these, also chest wall recurrences from breast cancer. Generally, the treatment of this peculiar type of tumor requires the coverage of large skin areas. In these cases, electrochemotherapy treatment by means of standard small size needle electrodes (an array of 0.73 cm spaced needles, which covers an area of 1.5 cm) is time-consuming and can allow an inhomogeneous coverage of the target area. We have previously designed grid devices suitable for treating an area ranging from 12 to 200 cm. In this study, we propose different approaches to study advantages and drawbacks of a grid device with needles positioned 2 cm apart. The described approach includes a numerical evaluation to estimate electric field intensity, followed by an experimental quantification of electroporation on a cell culture. The electric field generated in a conductive medium has been studied by means of 3-dimensio...
Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, r... more Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Prim...
Electrochemotherapy (ECT) is an effective local treatment for cutaneous metastasis. Treatment inv... more Electrochemotherapy (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. The aim of this study was to investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors which affect (beneficially or adversely) the outcome. 13 cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoural or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. 151 patients with metastatic melanoma were identified from the database, 114 of which had follow-up data of 60 days or more. 80 of these patients (73%) experienced an overall response (complete response + partial response = OR). 394 lesions were treated, of which 306 (77%) revealed an OR, 229...
Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-ski... more 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. 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...
Journal of experimental & clinical cancer research : CR, 2003
Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patient... more Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical differenc...
Hyperthermic isolation limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) and IFNg... more Hyperthermic isolation limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) and IFNgamma was pioneered by Liénard and Lejeune in 1988. The TNFalpha was empirically employed at a dosage of 3-4 mg, that is ten times the systemic maximum tolerated dose (MTD). After eighteen years from its first clinical application, more than 300 patients have been treated. The aim of this study is to clarify two major arguments: the TNFalpha dose and eligibility criteria for patient selection. A phase I-II study has previously been conducted in 20 patients with in-transit melanoma metastases using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. Twenty patients were treated and a complete pathological response of 70% was recorded, with no correlation between tumor response and TNFalpha. The dose of 1 mg of TNFalpha provided the best results regarding efficacy and toxicity. On the basis of this results a large phase II SITILO study was undertaken. Patients wit...
Background. Peristomal metastases are rare, but potentially associated with relevant morbidity. S... more Background. Peristomal metastases are rare, but potentially associated with relevant morbidity. Surgical resection, followed by stoma relocation, represent the gold standard in most patients. We describe electrochemotherapy (ECT), a minimally invasive method for locally-enhancing drug delivery by means of electric pulses, as an alternative approach. Patient and methods. A 49-year-old man with advanced gastric cancer developed skin metastases around an ileostomy site. The ulcerated and oozing tumor growth impaired patient’s quality of life due to continuous trouble in fitting the ostomy appliance, its poor adherence and consequent stools spillage. ECT consisted of a 20-minute course under mild general sedation. A bleomycin bolus of 15 000 IU/m2 was followed by the percutaneous application of multiple, 1.5 ms -long electric pulses by means of a needle electrode. Results. Post ECT course was uneventful and the patient was discharged on the same day. After one week, tumor nodules were f...
Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating dose... more Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating doses of TNF-alpha (0.5-3.3 mg) and standard doses of doxorubicin (bolus 0.7-1.4 mg/kg) at a tumor temperature of at least 41 degrees C, with the aim to ascertain the maximum tolerable dose (MTD) and the activity of TNF-alpha combined with doxorubicin in hyperthermic antiblastic perfusion (HAP) for patients with limb sarcomas, candidates for amputation. Tumor response was assessed both pathologically and radiologically. Severe systemic toxicity (WHO) was observed in only 2 patients. Locoregional toxicity (Wieberdink's) was grade I in 3 patients, grade II or III in 10 and grade IV in 5. A strict correlation between the TNF dosage and the grade of limb reaction was found, grade IV being retrieved only with TNF dose >1 mg and/or muscular temperature >41.5 degrees C. Tumor necrosis was evaluated in 16 patients: in 11 (68.8%) it scored more than 75% while in 5 it was 25 to 75%. Four cases (25%) had 100% tumor histological necrosis. Limb sparing surgery was feasible in 13 (81%). Our findings suggest that this is a well-tolerated and highly active regimen in HAP.
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