Electrochemotherapy for head and neck cancers: possibilities and limitations

Abstract

Head and neck cancer continues to be among the most prevalent types of cancer globally, yet it can be managed with appropriate treatment approaches. Presently, chemotherapy and radiotherapy stand as the primary treatment modalities for various groups and regions affected by head and neck cancer. Nonetheless, these treatments are linked to adverse side effects in patients. Moreover, due to tumor resistance to multiple drugs (both intrinsic and extrinsic) and radiotherapy, along with numerous other factors, recurrences or metastases often occur. Electrochemotherapy (ECT) emerges as a clinically proven alternative that offers high efficacy, localized effect, and diminished negative factors. Electrochemotherapy involves the treatment of solid tumors by combining a non-permeable cytotoxic drug, such as bleomycin, with a locally administered pulsed electric field (PEF). It is crucial to employ this method effectively by utilizing optimal PEF protocols and drugs at concentrations that do not possess inherent cytotoxic properties. This review emphasizes an examination of diverse clinical practices of ECT concerning head and neck cancer. It specifically delves into the treatment procedure, the choice of anti-cancer drugs, pre-treatment planning, PEF protocols, and electroporation electrodes as well as the efficacy of tumor response to the treatment and encountered obstacles. We have also highlighted the significance of assessing the spatial electric field distribution in both tumor and adjacent tissues prior to treatment as it plays a pivotal role in determining treatment success. Finally, we compare the ECT methodology to conventional treatments to highlight the potential for improvement and to facilitate popularization of the technique in the area of head and neck cancers where it is not widespread yet while it is not the case with other cancer types.

Keywords: FEM analysis; electrochemotherapy; head and neck cancer; pulsed electric fields; tumors.

Figure 1

Cancer statistics and head and neck cancer classification.

Figure 2

Number of publications and citations in electroporation head and neck cancer research area. Different colors represent the publication types.

Figure 3

Expected effects of electrochemotherapy in the context of oral cancer.

Figure 4

Multi-drug resistance causing mechanisms in cancer cells.

Figure 5

Cell response dependency on pulsed electric field strength and pulse duration. The red circle represents standard European Standard Operating Procedures of Electrochemotherapy treatment protocol (eight 100-µs-duration unipolar pulses with 1 Hz repetition frequency and 800–1,400 V/cm electric field strength (115).

Figure 6

Spatial electric field distribution in the tumor using plate and needle array electrodes: (A) tumor finite element model (FEM) using plate electrodes, (B) typical spatial electric field distribution using plate electrodes (vertical cross-section, ZY axis), (C) typical spatial electric field distribution using plate electrodes (horizontal cross-section, XY axis), (D) tumor FEM model using needle array electrodes, (E) typical spatial electric field distribution using needle electrodes (vertical cross-section, ZY axis), and (F) typical spatial electric field distribution using needle electrodes (horizontal cross-section, XY axis).