Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review

Abstract

BackgroundElectrochemotherapy 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.MethodsThe 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.ResultsA 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.ConclusionsThere 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.

Efficiency of electrochemotherapy with reduced bleomycin dose in the treatment of nonmelanoma head and neck skin cancer: Preliminary results

“…Only 1 of 28 tumors in the control group did not respond to the treatment, even though the patient received a standard dose of bleomycin (15 000 IU/m 2 ). A nonresponding tumor was the recurrence after previous surgery and, thus, possibly more refractory to electrochemotherapy as it was already suggested by other authors …”

“…A nonresponding tumor was the recurrence after previous surgery and, thus, possibly more refractory to electrochemotherapy as it was already suggested by other authors. 11,12 The rationale for the reduction of the bleomycin dose lays in the results of our recent study on the pharmacokinetics of bleomycin administered as a bolus dose in elderly patients (65 years or older, according to World Health Organization classification) with nonmelanoma skin and mucosal cancers treated with electrochemotherapy. 7 Analyzing prospectively collected data from 24 patients by using liquid chromatography coupled to high-resolution mass spectrometry, slow and a monophasic serum clearance of the drug was recorded with the rate of <500 mL/min and a half-time of 30 minutes.…”

The DAHANCA 32 study: Electrochemotherapy for recurrent mucosal head and neck cancer

“…Despite previous extensive treatment with irradiation, surgery, and chemotherapy, electrochemotherapy can be performed on recurrent head and neck carcinomas and deliver an objective response rate of 58%. Additionally, in this trial we have in line with recommendations tried to elucidate as many details as possible regarding the procedure, the mucosal reaction, and how to response evaluate afterward.…”

Electrochemotherapy as a single treatment or adjuvant treatment to surgery of cutaneous sarcoid tumours in horses: a 31‐case retrospective study

“…The main mechanism of electrochemotherapy is thus increased cytotoxicity of cisplatin due to its higher intracellular concentration. Other mechanisms, such as prolonged accumulation of the drug in the tumours due to the vascular lock caused by application of electric pulses to the tumour and induction of immune response due to the tumour antigen shedding into the tumour microenvironment and blood stream were also documented (Cemazar and others 2015, Campana and others 2016). …”

“…Consequently the concentration of the injected drug is much higher which leads to much higher efficacy in the treated area (Cemazar and others 1998). ECT is also used for the treatment of cutaneous and subcutaneous tumours in humans in more than 150 oncological centres throughout Europe (Miklavčič and others 2012, Mali and others 2013a,b, Campana and others 2016). …”