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 described 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, 1-min nanoelectroablation treatment.

Keywords: ablation; apoptosis; basal cell carcinoma; nanoelectroablation; nanosecond pulsed electric field.

Figure 1. Five BCCs treated on a 55 year old woman with basal cell nevus syndrome

A. 5 × 10 mm lesion treated with 100 p, 30 kV/cm over two regions to cover the entire lesion. Images indicate lesion appearance before and after nsPEF treatment as well as 2, 10 and 14 wk later. A histological section of each lesion collected at 14 wk is shown on the bottom. Lesion “A” was undetectable by 10 wk and histological analysis at 14 wk indicated a dermal scar characterized by horizontally oriented collagen bundles and an increased number of vertically oriented vessels. Carcinoma was not identified within the biopsied portion of this lesion. B. 5 mm-wide lesion treated with 100p, 30 kV/cm. Lesion was nearly gone by 10 wk and undetectable at 14 wk. Carcinoma was not identified within the biopsied portion of this lesion. C. 6 mm wide lesion treated with 500 pulses, 30 kV/cm. Histological analysis of biopsy indicated invasive squamous cell carcinoma, keratoacanthoma type, narrowly excised on plane of section examined. The cup-shared lesion invaginates into the dermis and is filled with keratin. Squamous cells show minimal atypia and cells at base of lesion have a glassy-appearing cytoplasm. D. 8 mm-long lesion treated with 380 pulses, 30 kV/cm. The electrode did not cover the entire lesion. Histology conducted at 14 wk shows skin with multiple buds and irregular proliferations of basaloid cells attached to the undersurface of the epidermis. The peripheral layer of basaloid cells shows nuclear palisading and there is focal retraction artifact between the tumor islands and surrounding stroma. Necrotic keratinocytes and mitotic figures are present among the tumor cells. E. 5 mm-wide lesion treated with 1000 pulses, 30 kV/cm. This lesion took longer to fade away. Histology conducted at 14 wk indicated a dermal scar, characterized by horizontally oriented collagen bundles and an increased number of vertically oriented vessels. Carcinoma is not identified within the biopsied portion of this lesion.

Figure 2. Five BCCs treated on two subjects

A–B: 46 year old woman. Lesion A was treated with 100 pulses, 30 kV/cm over two regions to cover the entire lesion with the 5 mm × 7 mm electrode coverage. Lesion was gone by 7 wk and histological analysis of the treated region at 11 wk indicated dermal scar, characterized by horizontally oriented collagen bundles and an increased number of vertically oriented vessels. Dermal melanophages are present within the superficial dermis. There is minimal lymphohistiocytic infiltrate present. Carcinoma is not identified within the biopsied portion of this lesion. Lesion B was treated with 500 pulses, 30 kV/cm. The treated region was removed for biopsy at 11 weeks. Sections show a dermal scar, characterized by horizontally oriented collagen bundles and an increased number of vertically oriented vessels. There is focal calcification and keloidal collagen present within the dermis. A lymphohistiocytic infiltrate is present surrounding the dermal fibrosis. Carcinoma is not identified within the biopsied portion of this lesion. C–E: Three BCCs treated on the scalp of a 60 year old male. Lesion C was treated in four regions with 100 pulses, 30 kV/cm. At 15 wk the entire treated region was removed for histology. Sections show skin with buds and irregular proliferations of basaloid cells attached to the undersurface of the epidermis. The peripheral layer of basaloid cells shows nuclear palisading and there is focal retraction artifact between the tumor islands and surrounding stroma. Necrotic keratinocytes and mitotic figures are present among the tumor cells. Lesion D was treated with 1000 pulses, 30 kV/cm. Entire treated region was removed at 15 wk and histological analysis indicated skin with seborrheic keratosis, including orthokeratotic hyperkeratosis, acanthosis, horn pseudocysts, and an epidermal proliferation composed of small, bland, cuboidal keratinocytes. This proliferation lacks significant cytologic atypia or mitotic activity. Dermal fibrosis is present. Lesion E was treated in two regions with 100 pulses, 30 kV/cm. The entire treated region was removed at 15 wk and histological analysis indicated seborrheic keratosis, including orthokeratotic hyperkeratosis, acanthosis, horn pseudocysts, and an epidermal proliferation composed of small, bland, cuboidal keratinocytes. This proliferation lacks significant cytologic atypia or mitotic activity. Dermal fibrosis is present.