Elsevier

European Journal of Cancer

Volume 138, October 2020, Pages 30-40
European Journal of Cancer

Original Research
Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008–2019)

https://doi.org/10.1016/j.ejca.2020.06.020Get rights and content

Highlights

  • Electrochemotherapy (ECT) is highly efficient in the treatment of cutaneous metastases.

  • ECT is efficient across tumour histologies.

  • ECT response is higher for smaller tumours.

  • Intravenous bleomycin was more efficient than intratumoural, in tumours more than 2 cm size.

  • Linear array electrodes were more efficient in tumours less than 3 cm size.

Abstract

Background

Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters.

Methods

Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field.

Results

Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration.

Conclusions

These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Introduction

Electrochemotherapy (ECT) is a targeted localised form of chemotherapy that has become increasingly established amongst the treatment options for cutaneous malignancy of skin and non-skin origin, since the publication of the Standard Operating Procedures over a decade ago [1,2]. ECT is now a recognised treatment option as part of the multi-disciplinary approach to cutaneous malignant disease across Europe, as evidenced by The National Institute for Health and Care Excellence, UK (NICE) guidance [3,4] and recent European consensus treatment documents for cutaneous squamous cell carcinoma (SCC), basocellular carcinoma, melanoma and Kaposi's sarcoma (KS) [[5], [6], [7], [8], [9], [10]]. Several articles describe the use of ECT for specific indications, including malignant melanoma (MM) [[11], [12], [13]], breast cancer [[14], [15], [16]], KS [17] and basal cell carcinoma (BCC) [[18], [19], [20]]. However, these have so far been unable to answer some important questions including any potential difference in response rate in accordance with tumour factors, such as histology, or local tissue factors, such as prior radiotherapy, and treatment parameters.

ECT uses the principle of electroporation in combination with a chemotherapeutic agent, either bleomycin or rarely cisplatin, to achieve localised tumour control [21]. A number of drugs have been investigated; however, bleomycin has by far the largest increase in efficacy after electroporation enhancing the cytotoxic effect several hundred fold resulting in the need for a once-only therapy [[22], [23], [24]].

The International Network for Sharing Practice in ECT is a pan-European collaboration of centres encompassing different specialities that treat cutaneous malignancy. The group has over the years published the first analysis of 52 patients in the database [15], and on outcomes for specific diseases such as cutaneous metastases from MM [12], from breast cancer [16], and cutaneous tumours in the head and neck region [18], as well as articles investigating specific topics of importance such as pain management [18]. A number of phase II studies have been very informative [13,[25], [26], [27]] but have not been able to answer questions of general importance with sufficient power. Now, we are in a position to conduct a more robust analysis of response rates amongst a large number of patients and investigating clinically significant variables due to data being accrued in a homogenous way.

In any treatment, there are a number of permutations that could affect a differential response to treatment. For ECT, this encompasses tumour-specific factors such as histotypes and tumour size, as well as factors that could influence the efficacy of successful electroporation. These include the technique used to deliver electroporation such as the route of administration (intravenous (i.v.) or direct intratumoural [IT] injection), the choice of delivery probe (such as linear or hexagonal probes), the electroporation parameters achieved measured by the current delivered, as well as the state of the recipient tissue most notably inherent skin fibrosis through previous treatments such as irradiation. These issues are addressed in this article with 987 patients, treated across European centres, using the same operating procedures, and uploaded in the same database, and results will serve to further guide the use of ECT.

Section snippets

Patients

Twenty eight participating centres entered treatment data between the start of the database in February 2008 and November 2019. Appropriate approvals were sought by each institution individually. Participation in the database collaboration was by signed agreement. Patient selection was based on institutional preferences, including referral after multi-disciplinary discussion for patients with symptomatic cutaneous metastasis, and some primary skin cancers when other treatment modalities failed

Patients

Twenty eight cancer centres across Europe prospectively uploaded anonymised treatment data to a common database on 1510 patients between February 2008 and November 2019. Of these, 987 patients with 2482 nodules had follow-up of more than 45 days and were included. The demographics of all patients and those with more than 45 days follow-up was similar (Table 1). A list of participating centres with number of registered patients may be found in Supplementary table [Table S1].

Nine hundred fourteen

Discussion

ECT has emerged as a consistent and reliable treatment option for patients with cutaneous malignancies of skin and non-skin origin [1,2,[13], [14], [15],18,26]. Complete and OR rates have remained high and consistent with initial studies [25] in this prospective real-world treatment data from 20 cancer centres across Europe, delivered by a variety of specialists. As data were entered into a common database, a number of previously unreported analyses have now been possible revealing subtle

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

The following authors have conflict of interest:

A.J.P.C. reports receiving travel fees for a meeting related to manuscript preparation by IGEA. F.d.T. is an employee of IGEA. J.O. reports receiving travel fees and accommodation fees from IGEA. L.G.C. reports receiving travel support for the International Network for Sharing Practice in Electrochemotherapy (InspECT) meeting from IGEA. D.M. reports receiving travel fees and accommodation fees for InspECT meeting from IGEA. A.D.M.R. reports

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