Arbeitsgruppe „ElectroPros“

Project Context: Cancer

Cancer is the second most common cause of death in the world today (WHO world cancer report 2014: 8.2 million cancer related deaths per year) and numbers are still rising rapidly in an aging population. Up to the year 2050, a growth in cancer patients of ~30% is estimated. Cancer is the name for the group of malignant tumor diseases. The common characteristic is the uncontrolled growth of tumor cells, that can destroy healthy tissue. The most frequent location of metastases is the liver: In many tumor diseases, liver metastasis is a critical factor for the survival of the patient. The epidemiological indicators increase significantly for this organ.

The traditional treatment methods in cancer care are surgery, systemic chemotherapy and radiotherapy. In the last decade, a new fourth branch in cancer treatment has developed and is gaining rapidly in relevance: minimally-invasive interventional treatments. These techniques limit the size of incisions needed and so lessen wound healing time, associated pain and risk of infection. As a consequence, they can significantly reduce the side-effects for the patient while still be able to destroy the tumor completely. In today’s tumor therapy, thermal ablations are the most common ones: The tumorous tissue is destroyed by either heat or freezing. Radiofrequencyablation (RFA) and Microwaveablation (MWA) are the most commonly used for liver metastases, but they are limited especially in the tumors location: As the produced heat can also destroy blood vessels or at least the blood flow cools down the tumor area, RFA and MWA can’t be used for tumors located near or on those vessels.

If there are induced too many and too big nanopores, the cell’s membrane is destroyed permanently and the cells dies because of apoptosis (irreversible EP). Otherwise the cell can repair their phospholipid bilayer and continue on with their normal cell functions (reversible electroporation). In this case, the nanopores can be used to enhance the uptake of pharmacological active substances like chemotherapeutics into the cell.

The medical treatment modalities based on EP are Irreversible Electroporation (IRE) and Electrochemotherapy (ECT). IRE is currently used in clinical settings for the treatment of liver, pancreas and lung cancer using the AngioDynamics NanoKnife. ECT is an established treatment modality for skin malignancies using the IGEA Cliniporator. One of the main advantages is, that these treatment options are non-thermal: They do not suffer from blood vessel cooling effects and also do not harm vessels (like hepatic arteries, hepatic and portal veins and intrahepatic bile ducts) or in general the blood flow.

For a more detailed introduction to the link “What is Electroporation?” below.

IRE as well as ECT offer a promising treatment alternative for patients, which are not eligible for surgical tumor resection or where systemic therapies are too demanding. Furthermore, combining IRE and ECT together with Optimizing this treatment to the individual patients, this combination is a revolutionary innovation idea in treatment of cancer. The potential reaches from drastically reducing side-effects for the patient, up to first time curative treatment for patients, which are currently considered as not curable.

Project Targets

EP-based treatments are promising methods, that could allow a highly selective curative tumor treatment. But therefore a software is needed, which allows this selective planning in a very accurate way. So the final goal is software, which allows the physician a patient individual planning, which means an accurate simulation of the electric field strength as an overlay in the patient’s 3D liver illustration, made of the patient’s CT DICOM images. Also the outlines for the thresholds of irreversible EP for IRE and reversible EP for ECT should be possible to display. Therefore a 3D DICOM-reconstruction software is needed, which is provided by the project partner Philips. For an accurate overlay several things has to be done:

• Informatics: Implement an electric field simulation into the reconstruction software.
• Retrospective data analysis: Which electric field density leads to which ablation zone?
• Electrode design: Which electrode geometries can be better adaptable to patient specifics tumors?
• Biological cell studies: Depending on the tumor type or the surrounding tissue type, which field strength thresholds leads to reversible / irreversible EP?
• Validation of the datasets.

Further Information: Publications by UKA and project team

• What is Electroporation? Slices from UKA Radiology.
• http://publications.rwth-aachen.de/record/699111
• https://www.ncbi.nlm.nih.gov/pubmed/30411673
• https://www.ncbi.nlm.nih.gov/pubmed/31101968