Treatment of vulvar cancer recurrences with electrochemotherapy – a detailed analysis of possible causes for unsuccessful treatment

Abstract

Background Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy. The biological features/determinants for the nonresponsiveness are not determined yet. Patient and methods A recurrence of vulvar squamous cell carcinoma was treated by electrochemotherapy using intravenous administration of bleomycin. The treatment was performed by hexagonal electrodes according to standard operating procedures. We analyzed the factors that could determine nonresponsiveness to electrochemotherapy. Results Based on the presented case of nonresponsive vulvar recurrence to electrochemotherapy, we hypothesize that the vasculature of the tumors prior to treatment may predict the response to electrochemotherapy. The histological analysis showed minimal presence of blood vessels in the tumor. Thus, low perfusion may reduce drug delivery and lead to a lower response rate because of the minor antitumor effectiveness of vascular disruption. In this case, no immune response in the tumor was elicited by electrochemotherapy. Conclusions In this case, of nonresponsive vulvar recurrence treated by electrochemotherapy, we analyzed possible factors that could predict treatment failure. Based on histological analysis, low vascularization of the tumor was observed, which hampered drug delivery and distribution and resulted in no vascular disrupting action of electro-chemotherapy. All these factors could contribute to ineffective treatment with electrochemotherapy.

Safety and Feasibility of Vulvar Cancer Treatment with Electrochemotherapy

“…Little is known about the safety and feasibility of electrochemotherapy treatment in gynecologic cancers. In the literature at present, there are only a few articles or clinical cases describing the use of electrochemotherapy in patients with vulvar or vaginal cancers for palliative purposes [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In these articles, detailed feasibility data are lacking.…”

“…In addition to being safe and effective as a form of monotherapy, electrochemotherapy can be successfully combined with other standard treatments, such as targeted therapies (vemurafenib and dabrafenib) [ 13 ] or immunotherapy (pembrolizumab) [ 14 ]. To date, only a few articles or clinical cases have been published describing the use of electrochemotherapy in patients with vulvar cancer for palliative purposes [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. In these articles, the safety and local efficacy of electrochemotherapy have been demonstrated; however, a detailed analysis of the safety and feasibility of electrochemotherapy in vulvar cancer patients is lacking.…”

Characterization of two distinct immortalized endothelial cell lines, EA.hy926 and HMEC-1, for in vitro studies: exploring the impact of calcium electroporation, Ca2+ signaling and transcriptomic profiles

“…Excessive influx and uptake of Ca 2+ in intracellular stores, such as the endoplasmic reticulum (ER) and mitochondria, signifies cell stress and can lead to irreversible Ca 2+ overload, resulting in cell death triggered by mitochondrial dysfunction and subsequent energy production failure [ 14 – 16 ]. Therefore, Ca 2+ has been investigated as an antitumor treatment in combination with electroporation (EP) as a nonmutagenic and inexpensive alternative to electrochemotherapy (ECT), which can induce tumor necrosis via ATP depletion [ 17 – 19 ]. In preclinical studies, calcium electroporation (CaEP) with local intratumoral administration of a Ca 2+ solution showed dose-dependent antitumor efficacy, with the number of tumors cured depending on tumor type [ 20 – 22 ].…”

Gene Immunotherapy of Colon Carcinoma with IL-2 and IL-12 Using Gene Electrotransfer

“…Another biomedical application of electroporation, in which cytotoxic drugs are introduced into tumours, is called electrochemotherapy. Electrochemotherapy is one of the ablative therapies for the treatment of superficial and also deep-seated tumours of various histologies [ 6 , 7 ].…”