Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy

ABSTRACT:  Electroporation is used to enhance drug diffusion and gene delivery into the cytosol. The combination of electroporation and cytotoxic drugs, electrochemotherapy (ECT), is used to treat metastatic tumor nodules located at the skin and subcutaneous tissue. The objective response rate following a single session of treatment exceeds 80%, with minimal toxicity for the patients. The efficacy of ECT in the bone and visceral metastasis is currently investigated, and Phase II studies have been completed. ECT has been used to treat skin primary tumors, except melanoma, and is under investigation for locally advanced pancreatic cancer. Early evidence suggests that treatment of tumor nodules with ECT recruits components of the immune system and eliciting a systemic immune response against cancer is a challenging clinical perspective. Considering the proven safety in several different clinical applications electroporation should be viewed as a clinical platform technology with wide perspectives for use in ECT, gene therapy and DNA vaccination

Modelling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case

Background: Breast cancer is the most common cancer in women worldwide and is the second most common cause of cancer death in women. Electrochemotherapy (ECT) used in early-phase clinical trials for the treatment of primary breast cancer resulted in a not complete tumor necrosis in most cases. The present study was undertaken to analyze the feasibility to use ECT to treat patients with histologically proven unifocal ductal breast cancer. In particular, results of ECT treatment in a clinical case are compared with the ones of a simplified 3D dosimetric model. Methods: This clinical study was conducted with the pulse generator Cliniporator Vitae (IGEA, Carpi, Italy). ECT procedures were performed according to ESOPE standard operating procedures. Five single needle electrodes were used with one positioned in the center of the tumor, and the other four distributed around the nodule. Histological images of the resected tumor are compared with the maps of the electric field obtained with a simplified 3D model in Comsol Multiphysics v 4.3. Results: The results of the clinical case demonstrated a reduced efficacy of the ECT treatment described. The proposed simple numerical model of the breast tumor located in a low conductive tissue suggests that this is due to the reduced electric field induced inside the tumor with such 5 electrodes placement. However, where the electric field is predicted higher than the reversible electroporation threshold (E > 400 V/cm), also the histological images confirm the necrosis of the target with a good agreement between the modeled and clinical results. Conclusions: The results suggest the dependence of the effectiveness of the treatment on the careful placement of the electrodes. A detailed planned procedure for the tumor analysis after the treatment is also needed in order to better correlate the single electrode positions and the histological images. Simulation models could be used to identify better electrodes configuration in planning the experimental protocol for ECT treatment of breast tumors

Next-generation ultra-compact calorimeters based on oriented crystals

Calorimeters based on oriented crystals provide unparalleled compactness and resolution in measuring the energy of electromagnetic particles. Recent experiments performed at CERN and DESY beamlines by the AXIAL/ELIOT experiments demonstrated a significant reduction in the radiation length inside tungsten and PbWO4, the latter being the scintillator used for the CMS ECAL, observed when the incident particle trajectory is aligned with a lattice axis within ∼1∘. This remarkable effect, being observed over the wide energy range from a few GeV to 1 TeV or higher, paves the way for the development of innovative calorimeters based on oriented crystals, featuring a design significantly more compact than currently achievable while rivaling the current state of the art in terms of energy resolution in the range of interest for present and future forward detectors (such as the KLEVER Small Angle Calorimeter at CERN SPS) and source-pointing space-borne γ-ray telescopes

Electrochemotherapy in the Treatment of Bone Metastases: A Phase II Trial

Introduction: Bone metastatic disease is a major cause of pain and decreased quality of life in patients with cancer. In addition to systemic therapy and pain control with narcotic analgesics, standard local treatments include palliation with radiation therapy and surgery. However, 20\u201330\ua0% of patients do not respond to conventional treatments, increasing the interest in alternative therapies. We present the results of a new minimally invasive technique in the treatment of bone metastases. Methods: Twenty-nine patients affected by painful bone metastases were treated with electrochemotherapy (ECT) from July 2009 to July 2011; the mean age was 60 years (range 37\u201387); 21 patients received a previous ineffective local treatment; the appendicular skeleton was affected in 15 patients while in 14 patients other sites were involved. ECT was performed using the Cliniporator Vitae under fluoroscopy or CT guidance depending on the site of the lesion. Clinical response was assessed using VAS scale and objective tumour response was evaluated according to the MD Anderson criteria for bone metastases. Results: All patients well tolerated the procedure and no intraoperative or postoperative complications were observed. At a mean follow-up of 7\ua0months, 24 patients were available for evaluation. 84\ua0% of the patients (20 out of 24) referred improvement of pain 6550\ua0% with reduction of narcotics consumption. Radiographic evaluation after 3\ua0months in 20 evaluable patients, showed \u201cpartial response\u201d in 1 patient, \u201cstable disease\u201d in 17 and \u201cprogression\u201d in two cases. Discussion: Results reported in this study demonstrated ECT to be safe and feasible in the treatment of painful bone metastases even when other previous treatments were ineffective. Pain and disease progression control was achieved in the majority of the patients with consequent improvement of quality of life. Conclusion: ECT should be considered a new feasible tool in the treatment of bone metastases in place or in combination with standard treatments; further developments are required to extend the use of this technique to spine metastases

Impact of the number of electric pulses on cell electrochemotherapy in vitro: Limits of linearity and saturation

International audienc

Transposon-Based, Targeted Ex Vivo Gene Therapy to Treat Age-Related Macular Degeneration (TargetAMD)

International audienc