Periodic Reporting for period 2 - ElectroPros (Training research pioneers by utilizing and validating the promise of electroporation for minimal invasive oncological treatments.)
Période du rapport: 2021-01-01 au 2022-12-31
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.
Due to this high societal burden of cancer, tumor therapy is a very important research area, connected to limits and side-effects of the current standard of care treatment. Furthermore, life expectancy for cancer patients is increasing, making quality of life and minimal side-effects of treatments an important issue. The traditional treatment methods in cancer care are surgery, systemic chemotherapy and radiotherapy. In the last decade, a new fourth pillar in cancer treatment has developed, namely minimally-invasive interventional treatment.
The Éuropean Industry Doctorate (EID) project ElectroPros focussed on research related to a new promising minimally-invasive cancer treatment procedure: Irreversible electroporation (IRE). A treatment method to kill tumor cells with electric fields. Four PhD candidates were hired to advance the research related to IRE. The EID program is unique because it enables the PhD candidates to be trained and research in the academic as well as the industrial sector.
Main outcomes of the ElectroPros project are simulation models to optimize treatment procedures and devices. Alternative methods to test the efficacy of developed devices, without need for animal experiments and computational algorithms to improve procedure planning which can be utilized in procedure planning software applications.
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.
Due to this high societal burden of cancer, tumor therapy is a very important research area, connected to limits and side-effects of the current standard of care treatment. Furthermore, life expectancy for cancer patients is increasing, making quality of life and minimal side-effects of treatments an important issue. The traditional treatment methods in cancer care are surgery, systemic chemotherapy and radiotherapy. In the last decade, a new fourth pillar in cancer treatment has developed, namely minimally-invasive interventional treatment.
The Éuropean Industry Doctorate (EID) project ElectroPros focussed on research related to a new promising minimally-invasive cancer treatment procedure: Irreversible electroporation (IRE). A treatment method to kill tumor cells with electric fields. Four PhD candidates were hired to advance the research related to IRE. The EID program is unique because it enables the PhD candidates to be trained and research in the academic as well as the industrial sector.
Main outcomes of the ElectroPros project are simulation models to optimize treatment procedures and devices. Alternative methods to test the efficacy of developed devices, without need for animal experiments and computational algorithms to improve procedure planning which can be utilized in procedure planning software applications.
The 4 ESR’s have been working in 4 knowledge area’s:
• Electrode (probe) design (UKA)
• Experimental verification (UKA)
• Multiphysics modelling (UKA / Philips)
• Optimization technologies (Philips)
For the University Hospital RWTH Aachen, the outcome of the project has changed our further development steps for IRE treatment of cancer for good. Originally, the focus was on preparing and conducting animal studies. Due through the pandemic, the project goals had been changed, as an animal study was not possible to perform. We moved to a more fundamental research on Electroporation effects, but also on the avoidance of animal trials.
• We proofed vegetable models to be sufficient for qualitatively electrode functional tests. Also we proofed MRI as an valid evaluation method even for the vegetable model, and optimized the MRI protocol for that use case. All further electrode device testing can now be made on this foundation.
• The second outcome are new electrode designs in computer simulations, which we now can test and evaluate in the vegetable model instead of animal trials. Also we proofed, that our previous developed prototype does not produce more heat than classic IRE, which was a main open critics in scientific discussions with the IRE-community.
• The third outcome of the cell culture trials are a perimeter for the thresholds on IRE vs ECT vs. no effect.
ElectroPros provided new means to UKA to further research on improving the effectiveness of electroporation-based cancer treatments, without having to rely on animal experiments. This has the potential to speed up development of this promising minimally invasive technique.
The main interest of Philips research in ElectroPros is related to methodologies for improved planning applications (sw tools) to integrate with Philips products to improve the minimal-invasive treatment of cancer.
Specific outcomes of the ElectroPros project of interest for further product development inside Philips:
• The algorithms developed for sensitivity analysis (SA), uncertainty quantification (UQ) and surrogate based inverse planning/optimization are extremely valuable and applicable to a broad range of healthcare applications, specifically but not solely within the oncology domain.
• To leverage in future and current applications the value of the developed algorithms, they are adapted and made available through the Philips internal algorithm catalogue. Such catalogue is an internal tool that aims at ensuring maintenance of Philips internal algorithms. This is essential to leverage existing assets/ knowledge with the goal of increasing development speed and reducing duplication of efforts.
• Electrode (probe) design (UKA)
• Experimental verification (UKA)
• Multiphysics modelling (UKA / Philips)
• Optimization technologies (Philips)
For the University Hospital RWTH Aachen, the outcome of the project has changed our further development steps for IRE treatment of cancer for good. Originally, the focus was on preparing and conducting animal studies. Due through the pandemic, the project goals had been changed, as an animal study was not possible to perform. We moved to a more fundamental research on Electroporation effects, but also on the avoidance of animal trials.
• We proofed vegetable models to be sufficient for qualitatively electrode functional tests. Also we proofed MRI as an valid evaluation method even for the vegetable model, and optimized the MRI protocol for that use case. All further electrode device testing can now be made on this foundation.
• The second outcome are new electrode designs in computer simulations, which we now can test and evaluate in the vegetable model instead of animal trials. Also we proofed, that our previous developed prototype does not produce more heat than classic IRE, which was a main open critics in scientific discussions with the IRE-community.
• The third outcome of the cell culture trials are a perimeter for the thresholds on IRE vs ECT vs. no effect.
ElectroPros provided new means to UKA to further research on improving the effectiveness of electroporation-based cancer treatments, without having to rely on animal experiments. This has the potential to speed up development of this promising minimally invasive technique.
The main interest of Philips research in ElectroPros is related to methodologies for improved planning applications (sw tools) to integrate with Philips products to improve the minimal-invasive treatment of cancer.
Specific outcomes of the ElectroPros project of interest for further product development inside Philips:
• The algorithms developed for sensitivity analysis (SA), uncertainty quantification (UQ) and surrogate based inverse planning/optimization are extremely valuable and applicable to a broad range of healthcare applications, specifically but not solely within the oncology domain.
• To leverage in future and current applications the value of the developed algorithms, they are adapted and made available through the Philips internal algorithm catalogue. Such catalogue is an internal tool that aims at ensuring maintenance of Philips internal algorithms. This is essential to leverage existing assets/ knowledge with the goal of increasing development speed and reducing duplication of efforts.
ElectroPros was part of the unique collaborative EID research program between PHILIPS and UKA, aiming for breakthroughs in minimally-invasive interventional oncology. Using our novel interdisciplinary approach, the ESRs delivered unique approaches and beyond state of the art technology which tackle the shortcomings of the current solutions. These new insights enable UKA and PHILIPS to make next steps in improving electroporation as a cancer treatment method and make it in future available to patients for difficult to treat tumors, like in pancreas.
Specifically, in following area's progress was realized:
• Biophysics predictive models. To optimize electroporation treatments, it is important to understand the physical phenomena that determine the effect of a treatment. Biophysics modelled are developed to describe these effects and form the basis for developing optimized treatment devices and planning the procedures.
• Treatment efficiency measurement. Experiments on cell suspensions to fundamentally investigate this topic are designed. Furthermore, plant-models (e.g. potatoes) were developed to study the electroporation effect in biological structures based on electrode settings. This reduces largely the need for using animal experiments.
• Electrode design and prototype realization. A device was designed, having a single electrode entrance point. This design will also offer improved control on electric field shape and strength in different directions. Due to the single electrode principle, positioning effort is much less and tumor spill risk is reduced. Also strategies like applying voltage to the needle while extracting can be explored to avoid tumor spill. This new design can in future potentially lead to improved outcomes.
• Procedure planning. Mathematical algorithms that propose an optimal positioning and driving of the electrode beforehand are crucial. Based on this, a constrained optimization problem is defined, giving as output position and driving of the electrode to kill the tumor cells and spare critical surrounding structures. Different methods (gradient-based, non-gradient based) for solving the constrained optimization problem are tested, where efficiency of solving (fast computation) is a prerequisite. These algorithms can feed into procedure planning applications for physicians, to optimize the treatment for the patient.
Summarizing, the ESR's of ElectroPros advanced the next steps in development for making electroporation in future a mature cancer treatment option for more patients.
Specifically, in following area's progress was realized:
• Biophysics predictive models. To optimize electroporation treatments, it is important to understand the physical phenomena that determine the effect of a treatment. Biophysics modelled are developed to describe these effects and form the basis for developing optimized treatment devices and planning the procedures.
• Treatment efficiency measurement. Experiments on cell suspensions to fundamentally investigate this topic are designed. Furthermore, plant-models (e.g. potatoes) were developed to study the electroporation effect in biological structures based on electrode settings. This reduces largely the need for using animal experiments.
• Electrode design and prototype realization. A device was designed, having a single electrode entrance point. This design will also offer improved control on electric field shape and strength in different directions. Due to the single electrode principle, positioning effort is much less and tumor spill risk is reduced. Also strategies like applying voltage to the needle while extracting can be explored to avoid tumor spill. This new design can in future potentially lead to improved outcomes.
• Procedure planning. Mathematical algorithms that propose an optimal positioning and driving of the electrode beforehand are crucial. Based on this, a constrained optimization problem is defined, giving as output position and driving of the electrode to kill the tumor cells and spare critical surrounding structures. Different methods (gradient-based, non-gradient based) for solving the constrained optimization problem are tested, where efficiency of solving (fast computation) is a prerequisite. These algorithms can feed into procedure planning applications for physicians, to optimize the treatment for the patient.
Summarizing, the ESR's of ElectroPros advanced the next steps in development for making electroporation in future a mature cancer treatment option for more patients.