Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients

doi:10.1016/j.ejso.2021.05.004

European Journal of Surgical Oncology

Volume 47, Issue 10, October 2021, Pages 2609-2617

https://doi.org/10.1016/j.ejso.2021.05.004 Get rights and content

Abstract

Introduction

Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions.

Materials and methods

102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered.

Results

105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5–52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0–1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up.

Conclusion

The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy.

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.

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Citation Excerpt :
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Thermal tumor ablation techniques including radiofrequency, microwave, LASER, high-intensity focused ultrasound and cryoablation are routinely used to treated liver, kidney, bone, or lung tumors. However, all these techniques are thermal and can therefore be affected by heat sink effect, which can lead to incomplete ablation, and thermal injuries of non-targeted tissues are possible. Under certain conditions, high voltage pulsed electric field can induce formation of pores in the cell membrane. This phenomenon, called electropermeabilization, is also known as “electroporation”. Under certain conditions, electroporation can be irreversible, leading to cell death. Irreversible electroporation has demonstrated efficacy for the treatment of liver and prostate cancers, whereas data are scarce regarding pancreatic and renal cancers. During reversible electroporation, transient cell permeability can be used to introduce cytotoxic drugs into tumor cells (commonly bleomycin or cisplatin). Reversible electroporation used in conjunction with cytotoxic drugs shows promise in terms of oncological response, particularly for solid cutaneous and subcutaneous tumors such as melanoma. Irreversible and reversible electroporation are both not thermal ablation techniques and therefore open a new promising horizon for tumor ablation.
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Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients

Abstract

Introduction

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patients

Results

Discussion

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgments

Eur J Cancer Suppl

Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol

Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach

Dermatol Ther

Low-voltage electrochemotherapy with low-dose methotrexate enhances survival in mice with osteosarcoma

Clin Orthop

Electrochemotherapy is effective in the treatment of rat bone metastases

Clin Exp Metastasis

Electrochemotherapy in the treatment of bone metastases: a phase II trial

World J Surg

RECIST 1.1-Update and clarification: from the RECIST committee

Eur J Cancer Oxf Engl

Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases

Acta Oncol Stockh Swed