Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation.

Current technology has limited applicability for electroporation based treatment of deep-seated tumors, and is in general, not optimized in terms of compliance with clinically relevant parameters. Here we present a novel electrode device developed for electrotransfer of antineoplastic drugs and genes to intracranial tumors in humans, and demonstrate a method to optimize the design (i.e. geometry) of the electrode device prototype to improve both clinical performance and geometrical tolerance (robustness). We have employed a semiempirical objective function based on constraints similar to those used in radiation oncology. The results show that small geometrical changes may yield a significant improvement. For example, a 2 mm displacement of 6 electrodes yields 14% better compliance with the clinical parameters, compared to the prototype, and additionally makes the electrode device less sensitive to random geometrical deviations. The method is readily applicable to other electrode configurations.

[1]  K. Breur,et al.  When and how can we improve precision in radiotherapy ? , 2022 .

[2]  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.

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

[4]  J Teissié,et al.  Electropermeabilization of mammalian cells. Quantitative analysis of the phenomenon. , 1990, Biophysical journal.

[5]  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 .

[6]  Julie Gehl,et al.  Physiological effects of high- and low-voltage pulse combinations for gene electrotransfer in muscle. , 2008, Human gene therapy.

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

[8]  Damijan Miklavčič,et al.  Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study , 2006 .

[9]  Damijan Miklavcic,et al.  The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals , 2005, IEEE Transactions on Biomedical Engineering.

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

[11]  M. Jaroszeski,et al.  Clinical applications of electrochemotherapy. , 1999, Advanced drug delivery reviews.

[12]  Julie Gehl,et al.  5041 Electrochemotherapy as palliative treatment for chest wall recurrence of breast cancer – initial results , 2009 .

[13]  D. Miklavcic,et al.  Numerical Models of Skin Electropermeabilization Taking Into Account Conductivity Changes and the Presence of Local Transport Regions , 2008, IEEE Transactions on Plasma Science.

[14]  L. Mir,et al.  Electrochemotherapy of spontaneous mammary tumours in mice. , 1991, European journal of cancer.

[15]  Eric Michielssen,et al.  Genetic algorithm optimization applied to electromagnetics: a review , 1997 .

[16]  Icru Prescribing, recording, and reporting photon beam therapy , 1993 .

[17]  M. Prausnitz,et al.  Quantitative study of electroporation-mediated molecular uptake and cell viability. , 2001, Biophysical journal.

[18]  J. Weaver,et al.  Changes in the passive electrical properties of human stratum corneum due to electroporation. , 1995, Biochimica et biophysica acta.

[19]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[20]  Dan Ferber,et al.  Safer and Virus-Free? , 2001, Science.

[21]  D Miklavcic,et al.  The importance of electric field distribution for effective in vivo electroporation of tissues. , 1998, Biophysical journal.

[22]  Richard Heller,et al.  Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  Tomaz Slivnik,et al.  Sequential finite element model of tissue electropermeabilization , 2005, IEEE Transactions on Biomedical Engineering.

[24]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.

[25]  Damijan Miklavcic,et al.  Feasibility of Employing Model-Based Optimization of Pulse Amplitude and Electrode Distance for Effective Tumor Electropermeabilization , 2007, IEEE Transactions on Biomedical Engineering.

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

[27]  Georges Noël,et al.  Conformity index: a review. , 2006, International journal of radiation oncology, biology, physics.

[28]  E. Gersing Impedance spectroscopy on living tissue for determination of the state of organs , 1998 .

[29]  P Raskmark,et al.  In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. , 1999, Biochimica et biophysica acta.

[30]  Raymond M. Leuthold,et al.  On the Use of Theil's Inequality Coefficients , 1975 .

[31]  Joos V Lebesque,et al.  Inclusion of geometric uncertainties in treatment plan evaluation. , 2002, International journal of radiation oncology, biology, physics.

[32]  André Wambersie,et al.  The International Commission on Radiation Units and Measurements , 2001, Journal of the ICRU.

[33]  A. Dutreix When and how can we improve precision in radiotherapy? , 1984, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.