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

BackgroundBreast 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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.

[1]  Damijan Miklavcic,et al.  Intraoperative electrochemotherapy of colorectal liver metastases , 2014, Journal of surgical oncology.

[2]  M. Lindstrom,et al.  A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries , 2007, Physics in medicine and biology.

[3]  Antonella Vecchiato,et al.  Bleomycin-Based Electrochemotherapy: Clinical Outcome from a Single Institution’s Experience with 52 Patients , 2008, Annals of Surgical Oncology.

[4]  M. Lindstrom,et al.  A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries , 2007, Physics in medicine and biology.

[5]  Rafael V. Davalos,et al.  Treatment of breast cancer through the application of irreversible electroporation using a novel minimally invasive single needle electrode , 2010, Breast Cancer Research and Treatment.

[6]  Damijan Miklavcic,et al.  Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors , 2012, Medical and Biological Engineering and Computing.

[7]  Rafael V. Davalos,et al.  Experimental Characterization and Numerical Modeling of Tissue Electrical Conductivity during Pulsed Electric Fields for Irreversible Electroporation Treatment Planning , 2012, IEEE Transactions on Biomedical Engineering.

[8]  B. Stewart,et al.  World cancer report 2014. , 2014 .

[9]  M Fini,et al.  Ablation of bone cells by electroporation. , 2010, The Journal of bone and joint surgery. British volume.

[10]  Damijan Miklavčič,et al.  Electrochemotherapy: from the drawing board into medical practice , 2014, BioMedical Engineering OnLine.

[11]  F. Marincola,et al.  Electrochemotherapy for the management of melanoma skin metastasis: a review of the literature and possible combinations with immunotherapy , 2014, Archives of Dermatological Research.

[12]  I. Fentiman,et al.  Radiofrequency ablation in the treatment of primary breast cancer: no surgical redundancies yet , 2008, International journal of clinical practice.

[13]  C Gabriel,et al.  The dielectric properties of biological tissues: I. Literature survey. , 1996, Physics in medicine and biology.

[14]  L. Pina,et al.  Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy. , 2008, Brachytherapy.

[15]  Damijan Miklavcic,et al.  Robustness of Treatment Planning for Electrochemotherapy of Deep-Seated Tumors , 2010, The Journal of Membrane Biology.

[16]  T. Jarm,et al.  Electrochemotherapy , 2011, Technology in cancer research & treatment.

[17]  Damijan Miklavcic,et al.  Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation , 2012, Physics in medicine and biology.

[18]  Damijan Miklavcic,et al.  Real time electroporation control for accurate and safe in vivo non-viral gene therapy. , 2007, Bioelectrochemistry.

[19]  P. Queirolo,et al.  Electrochemotherapy for the management of cutaneous and subcutaneous metastasis: A series of 39 patients treated with palliative intent , 2014, Journal of surgical oncology.

[20]  Damijan Miklavčič,et al.  Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy , 2006 .

[21]  A. Zupanic,et al.  Numerical Modeling and Optimization of Electric Field Distribution in Subcutaneous Tumor Treated With Electrochemotherapy Using Needle Electrodes , 2008, IEEE Transactions on Plasma Science.

[22]  Jon F Edd,et al.  Mathematical Modeling of Irreversible Electroporation for Treatment Planning , 2007, Technology in cancer research & treatment.

[23]  Thomas L Ellis,et al.  A Parametric Study Delineating Irreversible Electroporation from Thermal Damage Based on a Minimally Invasive Intracranial Procedure , 2011, Biomedical engineering online.

[24]  R. Simmons,et al.  Cryoablation of Early-Stage Breast Cancer: Work-in-Progress Report of a Multi-Institutional Trial , 2004, Annals of Surgical Oncology.

[25]  A. Testori,et al.  Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach , 2010, Dermatologic therapy.

[26]  Eko Supriyanto,et al.  Measurement of bioelectric and acoustic profile of breast tissue using hybrid magnetoacoustic method for cancer detection , 2013, Medical & Biological Engineering & Computing.

[27]  A V Korjenevsky,et al.  Dual-frequency electrical impedance mammography for the diagnosis of non-malignant breast disease. , 2008, Physiological measurement.

[28]  C. Collins,et al.  Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes , 2006 .

[29]  Mattia Ronchetti,et al.  Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. , 2014, Future oncology.

[30]  Damijan Miklavcic,et al.  Modeling of electric field distribution in tissues during electroporation , 2013, Biomedical engineering online.

[31]  S. Singletary,et al.  Radiofrequency ablation of early-stage invasive breast tumors: an overview. , 2002, Cancer journal.

[32]  C. Cabula.  Neoadjuvant electrochemotherapy of breast cancer: our experience on first case treated in Italy , 2013, Updates in Surgery.

[33]  Damijan Miklavcic,et al.  Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy , 2010, Biomedical engineering online.

[34]  Rafael V. Davalos,et al.  The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems , 2009, Annals of Biomedical Engineering.

[35]  Damijan Miklavčič,et al.  Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software , 2013, The Journal of Membrane Biology.

[36]  L. Mir,et al.  Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. , 1988, Biochemical pharmacology.