Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: a protocol for a systematic review and meta-analysis

Abstract

Electrochemotherapy has emerged as a valuable tool in the treatment of cutaneous malignancies that are unamenable to surgical resection. Despite growing recognition and recommendation in national guidelines, to date, no Level 1 evidence exists comparing its use to radiotherapy in the management of cutaneous malignancies. A systematic review and meta-analysis will be undertaken in line with the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. A comprehensive search strategy will be applied to MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov from the time period from inception to December 2021. Supplementary searches of the grey literature will also be undertaken. Studies in humans which compare treatment with electrochemotherapy to radiotherapy and report tumour response with at least a 4-week follow-up will be eligible. Studies will be included regardless of publication language or country of origin. Screening of studies and data extraction will be undertaken independently by two authors. Our primary outcome will be tumour volume response according to Response Evaluation Criteria in Solid Tumors. We will also extract any secondary outcomes reported, such as patient-reported outcome measures, pain, toxicity/adverse events and progression-free survival. Included studies will be assessed for risk of bias using recognized tools. Evidence quality will be appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. If studies are of acceptable clinical homogeneity and suitable data is extracted, a meta-analysis will be performed. If adequate data are present, various subgroup analyses will be performed. Publication bias will be assessed using a funnel plot and Egger’s test. PROSPERO CRD42021285415

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis

“…The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews [ 19 ] with the protocol ID CRD42021285415 and has been published in a peer-reviewed journal [ 20 ]. A copy of the protocol registered on PROSPERO is provided in the supporting information.…”

“…All studies comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from other primary solid organ malignancies were eligible for inclusion. Criteria for study selection were defined using the Population, Intervention, Comparison, Outcome (PICO) framework outlined in the pre-published protocol [ 20 ].…”

“…In our pre-published protocol we planned to undertake a meta-analysis including sub-group analyses if there was suitable extraction of clinically homogenous data [ 20 ]. However due the paucity of the literature this was not possible.…”

Electrochemically Enhanced Delivery of Pemetrexed from Electroactive Hydrogels

“…Conducting polymer-based electrode coatings enable delivery of drugs in the proximity of the site at which the electrodes are implanted, which is potentially impactful for electrochemotherapy which functions by electroporation of the cancerous tissue shortly after injection of anticancer drugs such as bleomycin or cisplatin [56][57][58][59][60]. Electrochemotherapy functions through a variety of mechanisms, including: the cytotoxic effect of the chemotherapeutic which is enhanced by electroporation; vasoconstriction of tumor blood vessel for several hours due to sympathetic nerve stimulation which reduces drug washout from the tumor; vascular disruption due to cytotoxicity towards the endothelial cells of tumor blood vessels; the immune response to immunogenic cell death and enhanced tumor antigen expression [61][62][63]. Electrochemotherapy has been used to enhance the delivery of a variety of drugs [59,60,[64][65][66][67][68], and has been observed to be a swift, safe and effective treatment method for cancers that tends to enhance the quality of life of patients [69][70][71][72][73].…”