TMS Electrochemotherapy for Glioblastoma Multiforme

The proposed project aims to develop novel electrochemotherapeutic treatment of glioblastoma multiforme (GBM). Standard treatment has limited effect on survival and quality of life. Electrochemotherapy is a novel and promising treatment, which has demonstrated convincing results in the treatment of various types of carcinoma. The treatment is based on a combination of electrical current stimulation of tumor cells and simultaneous administration of chemotherapeutic drugs. Electrochemotherapy works by inducing an electrical current between implanted electrodes in the tumor tissue, causing electroporation of the cancer cell membranes, and thereby increasing the cellular permeability and drug uptake. Electrochemotherapy has proven to be an efficient way of considerably increasing the potency of the chemotherapeutic drug bleomycin in malignant cells in skin tumors and carcinoma metastases, and thereby increasing cytotoxicity of the drug locally in the tumor tissue. This allows for treatment with lower doses of chemotherapeutic drugs and more defined, local area of effect, thus decreasing systemic effects. The investigators propose to use a novel non-invasive and safe technique called focused transcranial magnetic stimulation (focused TMS) to induce electrical current in the tumor tissue. TMS is a safe and widely implemented technology used to treat multiple neurological diseases such as pain, depression and stroke. Studies have shown that effective electroporation of cell membranes can be obtained using induction of electromagnetic fields in a cell suspension, and new focused TMS further enables focused treatment of selected brain regions without surgical intervention and, thereby focusing chemotherapeutic treatment to pathological tissue and avoiding surgery related brain tissue damage. Additionally, TMS transiently increases blood-brain barrier permeability, theoretically allowing increased uptake of chemotherapeutic drugs in the target area. This addresses a significant challenge in the treatment of brain cancer, as most cytotoxic drugs have fairly limited ability to pass the blood brain barrier. The intention of this research project is to investigate the therapeutic potential of focused TMS as an alternative non-invasive source of current induction and thereby means to treat several types of brain cancer with electrochemotherapy.

Inclusion Criteria: Newly diagnosed and histologically confirmed glioblastoma multiform MGMT gene methylation If age < 70, eligibility to comply with the Stupp radio chemotherapy regimen If age > 70, eligibility for stand alone chemotherapeutic treatment Ability to comply with the proposed TMS treatment Use of validated anti-conception for fertile female participants in concordance with guidelines provided by the Danish Health and Medicines Authority Exclusion Criteria: Pregnancy or nursing Other conditions that may contraindicate the use of transcranial magnetic stimulation Implanted pacemaker or metal contraindicating MRI-scan