Endoscopic calcium electroporation for colorectal cancer: a phase I study.

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Calcium Electroporation for Keloids: A First-in-Man Phase I Study.

BACKGROUND: Keloid scarring is a pathologic proliferation of scar tissue that often causes pruritus, pain, and disfigurement. Keloids can be difficult to treat and have a high risk of recurrence. Recent studies have shown promising results in the treatment of cutaneous metastases with intralesional calcium combined with electroporation (calcium electroporation). As calcium electroporation has shown limited side effects it has advantages when treating benign keloid lesions, and on this indication we performed a phase I study. METHODS: Patients with keloids were treated with at least 1 session of calcium electroporation and followed up for 2 years. Calcium was administered intralesionally (220 mM) followed by the application of eight 100-µs pulses (400 V) using linear-array electrodes and Cliniporator (IGEA, Italy). Treatment efficacy was evaluated clinically (size, shape, erythema), by patient self-assessment (pruritus, pain, other) and assessed histologically. RESULTS: Six patients were included in this small proof of concept study. Treatment was well tolerated, with all patients requesting further treatment. Two out of 6 patients experienced a decrease in keloid thickness over 30%. A mean reduction of 11% was observed in volume size, and a mean flattening of 22% was observed (not statistically significant). Five out of 6 patients reported decreased pain and pruritus. No serious adverse effects or recurrences were observed over a mean follow-up period of 338 days. CONCLUSION: In this first phase I clinical study on calcium electroporation for keloids, treatment was found to be safe with minor side effects. Overall, patients experienced symptom relief, and in some patients keloid thickness was reduced.

Calcium electroporation induces tumor eradication, long-lasting immunity and cytokine responses in the CT26 colon cancer mouse model.

Electroporation is used in cancer treatment because of its ability to increase local cytotoxicity of e.g. bleomycin (electrochemotherapy) and calcium (calcium electroporation). Calcium electroporation is a novel anticancer treatment that selectively kills cancer cells by necrosis, a cell death pathway that stimulates the immune system due to high release of antigens and "danger signals." In this exploratory study, we aimed to investigate whether calcium electroporation could initiate an anticancer immune response similar to electrochemotherapy. To this end, we treated immunocompetent balb/c mice with CT26 colon tumors with calcium electroporation, electrochemotherapy, or ultrasound-based delivery of calcium or bleomycin. High treatment efficiency was observed with 100% complete remission in all four groups (12/12 with complete remission in each treatment group). In addition, none of the surviving mice from these groups formed new tumors when re-challenged with CT26 cancer cells 100-d post treatment, whereas mice challenged with different cancer cells (4T1 breast cancer) all developed tumors. Treatment of immunodeficient mice with calcium electroporation and electrochemotherapy showed no long-lasting tumor response. Calcium electroporation and electrochemotherapy was associated with a release of High Mobility Group Box 1 protein (HMGB1) in vitro (p = 0.029) and a significant increase of the overall systemic level of pro-inflammatory cytokines in serum from the treated mice (p < 0.003). These findings indicate that calcium electroporation as well as electrochemotherapy could have a role as immune stimulators in future treatments.

[Electrochemotherapy for treatment of cutaneous metastases]. / Elektrokemoterapi til behandling af kutane metastaser.

Cutaneous metastases occur in up to 9% of all patients with cancer and may cause discomfort and stigmatization. Electrochemotherapy is a local treatment using electric pulses to permeabilize cell membranes, enabling chemotherapy, such as bleomycin, to enter the cells and increase the cytotoxic effect by at least 300-fold. Electrochemotherapy is an efficient, once only treatment for cutaneous metastases with an objective response of 62-99%. Electrochemotherapy can reduce discomfort such as ulceration, oozing, bleeding and pain. Adverse events depend on the size of treatment area, but are very limited.