First‐in‐human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method

Abstract

This nanoelectroablation therapy effectively treats subdermal murine allograft tumors, autochthonous basal cell carcinoma (BCC) tumors in Ptch1+/−K14-Cre-ER p53 fl/fl mice, and UV-induced melanomas in C57/BL6 HGF/SF mice. Here we describe the first human trial of this modality. We treated 10 BCCs on three subjects with 100–1000 electric pulses 100 ns in duration, 30 kV/cm in amplitude, applied at 2 pulses per second. Seven of the 10 treated lesions were completely free of basaloid cells when biopsied and two partially regressed. Two of the 7 exhibited seborrheic keratosis in the absence of basaloid cells. One of the 10 treated lesions recurred by week 10 and histologically had the appearance of a squamous cell carcinoma. No scars were visible at the healed sites of any of the successfully ablated lesions. One hundred pulses were sufficient for complete ablation of BCCs with a single, one minute nanoelectroablation treatment.

Cell membrane permeabilization by 12-ns electric pulses: Not a purely dielectric, but a charge-dependent phenomenon

“…(8), where c alu is the aluminum's specific heat capacity (c alu = 0.897 J/(g·K), d alu is the mass density of aluminum (d alu = 2.7 × 10 6 g/m 3 ), V medium is the volume of the cell suspension (V medium = 0.4 cm 3 ), and V alu is the volume of the electrodes (V alu = 0.64 cm 3 ). In that case, the temperature increase caused by 100 pulses of 12 ns and 4.3 MV/m is approximately 2.3°C.…”

“…This technique is nowadays routinely used in research laboratories and clinics e.g. to treat cancerous tissues [4][5][6][7][8]. In traditional electropermeabilization, pulse parameters can be chosen over a wide range and still lead to a successful permeabilization of cells.…”

Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

“…UCSF Benioff Children’s Hospital Oakland conducted the first clinical trial to treat skin cancer with nsPEFs (NCT01463709). Of 10 basal cell carcinomas treated, 7 became completely free of basaloid cells, 2 were partially ablated, and 1 recurred by week 10, with the appearance of squamous cell carcinoma31.…”

The cytotoxic synergy of nanosecond electric pulses and low temperature leads to apoptosis

“…Despite this incomplete knowledge, nsEP have already been successfully used for cancer ablation in animal models and in human trials2125262728. For instance, 300 ns pulses caused complete remission with no recurrence of murine melanomas in one treatment28.…”

“…For instance, 300 ns pulses caused complete remission with no recurrence of murine melanomas in one treatment28. In humans, 100 ns pulses caused regression of basal cell carcinoma lesions, with no scarring and no significant side effects27. One major obstacle to a wider use of nsEP in the clinic is the limited output voltage of the existing pulse generators, which limits the size of the ablation zone thus requiring multiple electrode insertions and exposures when treating bigger tumors.…”