Promising outcomes are being reported from clinical trials investigating Nano-Pulse Stimulation technology to treat nodular basal cell carcinoma and cutaneous, non-genital warts.
Accumulating data show promise for Nano-Pulse Stimulation technology (NPS, Pulse Biosciences) in the treatment of nodular basal cell carcinoma (nBCC) and cutaneous non-genital warts.
The results were presented at the 2020 virtual meeting of the American Society for Laser Medicine and Surgery. Christopher Harmon, M.D., who practices Mohs surgery and aesthetic dermatology in Birmingham, Ala., is an investigator in the nBCC study.
“Nodular BCCs are characterized by discrete large or small nests of basaloid cells in the papillary or reticular dermis,” he says. “Because of the varying degrees and unknown penetration of these deep cellular ‘nests,’ treatment typically requires surgical excision with wide margin control. NPS is exciting because early evidence indicates it can eliminate nBCCs with minimal scarring compared with conventional treatment.”
NPS is performed using a treatment tip containing a microarray of needles that deliver high amplitude, ultrashort electrical bursts to target lesion cells in the epidermis to deep dermis. The energy pulses cause transient nanoporation of the outer cellular membrane, altering the function of internal cellular organelles, including mitochondrial membrane and endo-plasmic reticulum.
This disruption ultimately leads to regulated cell death without any thermal effect or damage to surrounding acellular skin structures. In addition, the treatment is thought to stimulate an adaptive immune response that may contribute to clearing malignant lesions and warts.
Nodular BCC outcomes
The nBCC pilot study enrolled seven patients with a non-facial nBCC. They first underwent a pretreatment 3-mm biopsy for diagnostic confirmation and a blood draw for isolation of peripheral blood mononuclear cells. The NPS treatment was applied to only a portion of the tumor. The response was evaluated three to 12 weeks later with excision of the entire lesional area for histopathologic examination and a repeat
blood draw to identify evidence of an immune response. Treating only a portion of the tumor allowed researchers to validate the effectiveness of NPS through the histopathological examination, Dr. Harmon says.
As enrollment progressed, NPS energy settings were titrated down to find the “sweet spot” providing an optimal balance of efficacy and safety. The first two patients were treated with 15.5 J of energy (310 mJ/mm3). The energy was decreased by 50% for the next three patients to 7.7 J (155 mJ/ mm3), and then lowered by another 50% (3.9 J, 75 mJ/mm3) in the last two cases.
“We found that all of the energy levels were 100% effective. While tumor remained in the untreated area, the NPS-treated zones were consistently clear of nBCC. The biopsies also showed no clinical or histologic evidence of dermal scarring in the patients treated with the two lower energy settings,” Dr. Harmon says. “We were also encouraged to see infiltration of CD8+ T-cells in the untreated area in some histologic samples, which supports the idea that NPS induces a host immune response that may be part of its mechanism for tumor clearance.”
Based on positive findings of this early feasibility study, ongoing and future planned studies will further evaluate the two lower NPS energy settings of 75 or 155 mJ/mm3 to determine if treating the entire visible nBCC will achieve the study endpoint of histology-confirmed BCC elimination.
Although the study is enrolling patients with nBCC, Dr. Harmon believes NPS will also be studied as a minimally invasive option for clearing any BCC classified as low risk according to NCCN guidelines.
“We chose it to study nodular lesions because superficial BCCs may be removed entirely by the pretreatment shave biopsy performed for diagnostic confirmation. Further studies might investigate its use for superficial BCCs or other low-risk BCCs on the trunk and extremities,” Dr. Harmon says.
He notes that NPS technology might also have a role for treating aggressive BCCs on the face. Because those lesions can have a very deep component, modified probes that have longer microneedles and an insulated sheath may be tested for these deeper lesions.
Promise for challenging warts
Interim data from an expansion of a study investigating NPS treatment for cutaneous, non-genital warts was presented by E. Victor Ross, M.D., director, Laser and Cosmetic Dermatology Center, Scripps Clinic, San Diego. According to Dr. Ross, this pivotal clinical study included additional sites, an increased number of subjects and the treatment of warts across more anatomic areas, which enabled broader use of NPS to treat this difficult group of skin lesions.
He reported preliminary findings from 27 patients who had a total of 87 warts treated. The hands (n=39), feet (n=19), legs (n=10) and knees (n = 8) were the most common sites. Efficacy was high overall, with the best clearance rates observed for warts on the knee (100%), hands (90%) and leg (80%); 10 (53%) of the 19 warts on the foot were cleared. None of the warts that were eliminated showed evidence of recurrence at follow-up 60 days post-treatment.
“Our most recent data shows a continuing trend toward elimination of the majority of warts with one or two treatments,” Dr. Ross notes. “Cells are the real target of this technology, so any parts of the skin that are more cellular in nature versus stromal in nature will be more vulnerable to NPS energy,” he adds.
The potential for viral plume generated during treatment was investigated as a safety endpoint in a sub-cohort by stationing a sensitive particulate counter near the wart as NPS energy was being delivered. The results showed no evidence that the procedure resulted in aerosol emission of particles.
“Thermal-based cutaneous procedures may produce debris that contain dust, chemicals and infectious material. The absence of plume with NPS technology may be an important safety benefit for physicians and their patients,” Dr. Ross says. “The next steps for the wart protocol are expected to include testing tips with longer microneedles for deeper warts and evaluating optimal follow-on treatment intervals for the subset of warts that did not clear in a single procedure session.”
Dr. Harmon is a consultant to and member of the scientific advisory board for Pulse Biosciences. Dr. Ross is a consultant to and received research support from Pulse Biosciences.