Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients
Introduction
Bone metastases are frequent events in patients with cancer (1.5 million cases worldwide/year). New medical treatments have made it possible to extend the life expectancy of these patients, though it is important to focus on improving the quality of life (QoL) of patients with metastatic bone disease (MBD). Surgery is often required for pathological or impending fractures. Radiation therapy, as an alternative or completion to surgery, is not always effective; moreover, it cannot exceed the limit dose on the same site, therefore it cannot be repeated in the event of poor efficacy or local relapse of the disease.
In metastatic patients, Electrochemotherapy (ECT) is a palliative minimally invasive oncologic treatment. It consists in the combination of electric field and a single intravenous administration of chemotherapy drug. The cellular membranes increase their permeability if exposed to an external electric field so that not permeable molecules can diffuse into the cytosol (electroporation): this increases drug diffusion into the cell cytosol, thus its toxicity [[1], [2], [3]].
Preclinical in vivo studies showed that ECT is effective for the treatment of experimentally induced bone metastases and does not damage the mineral structure of the bone and its regenerative capacity [4,5]. These data supported the clinical use of ECT in patients with skeletal metastases.
In 2016, a phase II clinical trial was conducted on 29 patients with bone metastases [6]. Results demonstrated the safety and effectiveness of the procedure: 84% of the patients showed pain relief ≥50%, with reduction of narcotics consumption, and amelioration of QoL.
The purposes of this multicentre study are to confirm the safety of ECT treatment, its efficacy based on RECIST-PERCIST criteria, its effectiveness in improving both pain relief and patients QoL and finally to identify appropriate operating procedures in different MBD conditions.
Section snippets
Patients
Patients were treated in 11 centres between March 2014 and February 2020. All patients’ data were recorded a shared database (http://reinbone.wng.it) protected by security passwords. Clinical information uploaded included: demographics, diagnosis, stage of disease, site and size of the treated bone lesion, previous treatments, performance status, detailed information on ECT session, adverse events, side effects, response, quality of life indicators, follow-up. Approval from ethics committee and
Results
Data on 102 patients have been collected in 11 centres from Italy and France. Median age of patients was 63 years (range 38–91 yrs) and median time since diagnosis of the primitive tumour was 3 years (range 0–22 yrs). Descriptive statistic of the cohort of patients is reported in Table 1.
In 2 cases the target lesion was close to the joint plane (acetabulum), and no joint lesions were observed after treatment. Ninety-nine patients underwent a single ECT session, while 3 underwent 2 ECT sessions,
Discussion
Metastatic bone involvement is one of the major threat for oncologic patients, implying severe pain, QoL reduction, poorer prognosis, and risk of pathological fracture [10].
Local tumour control and pain relief are the two main goals to achieve in the treatment of MDB. While radiation therapy has a well-established role in local treatment of bone metastases, less is known about the effective contribution of other alternative local therapies such as image guided thermal ablation (cryotherapy and
CRediT authorship contribution statement
Laura Campanacci: Conceptualization, Formal analysis, Writing – original draft, Conception and design of study, analysis and/or interpretation of data, Drafting the manuscript, revising the manuscript critically for important intellectual content. Giuseppe Bianchi: Funding acquisition, acquisition of data. Costantino Errani: Funding acquisition, acquisition of data. Giovanni Ciani: Funding acquisition, acquisition of data. Giancarlo Facchini: Funding acquisition, Formal analysis, Writing –
Declaration of competing interest
The authors declare that there is no conflict of interest with the trademarks included in the manuscript. All authors disclose no personal, financial or non-financial competing interests. Francesca de Terlizzi and Matteo Cadossi are IGEA employers.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgments
We thank Simona Salati for editorial and linguistic assistance and for support with preparation of this manuscript.
References (17)
- et al.
Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study
Eur J Cancer Suppl
(2006) - et al.
Electrochemotherapy - emerging applications technical advances, new indications, combined approaches, and multi-institutional collaboration
Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol
(2019) - et al.
Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach
Dermatol Ther
(2010) - et al.
Low-voltage electrochemotherapy with low-dose methotrexate enhances survival in mice with osteosarcoma
Clin Orthop
(2004) - et al.
Electrochemotherapy is effective in the treatment of rat bone metastases
Clin Exp Metastasis
(2013) - et al.
Electrochemotherapy in the treatment of bone metastases: a phase II trial
World J Surg
(2016) - et al.
RECIST 1.1-Update and clarification: from the RECIST committee
Eur J Cancer Oxf Engl
(1990 2016) - et al.
Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases
Acta Oncol Stockh Swed
(2018)
Cited by (18)
Susceptibility of various human cancer cell lines to nanosecond and microsecond range electrochemotherapy: Feasibility of multi-drug cocktails
2023, International Journal of PharmaceuticsIrreversible electroporation and electrochemotherapy in oncology: State of the art
2022, Diagnostic and Interventional ImagingCitation Excerpt :A feasibility study on locally advanced pancreatic cancer was recently published on five patients [73]. From a multicenter, prospective study on 102 patients, ECT should also be considered as an alternative and safe treatment for metastatic bone disease as it has appeared to be a valid tool for their treatment with effectiveness on both pain relief and local tumor control [74]. There is a lot of ongoing studies on electroporation with 292 studies registered on the website clinicaltrial.gov (https://clinicaltrials.gov/ct2/results?cond=&term=electroporation&cntry=&state=&city=&dist=) at the date of September 29, 2022.
Bone ablations in peripheral skeleton: Rationale, techniques and evidence
2022, Techniques in Vascular and Interventional RadiologyCitation Excerpt :Moreover, due to the selective conductivity of this procedure, it can be performed without being injurious to sensitive structure such as the spinal cord or nerves.15 Recently, a clinical trial using reversible electroporation with bleomycin (electrochemotherapy (ECT)) demonstrates the ability of ECT to be an effective and safe treatment for metastatic bone disease.16 These procedures can be performed under conscious sedation or general anesthesia to bring to the patient more comfort and to allow the operator to accurately introduce the needle into the target lesion.
Electrochemotherapy in Aggressive Hemangioma of the Spine: A Case Series and Narrative Literature Review
2024, Journal of Clinical MedicineReoperation after surgery for bone metastasis of renal cell carcinoma
2024, Journal of Surgical OncologyInterventional Oncology: 2024 Update
2024, Canadian Association of Radiologists Journal