Implanted dynamic electric field therapy for glioblastoma: preclinical safety and efficacy of intratumoral modulation therapy.

BACKGROUND

Electric field-based approaches show therapeutic impact against glioblastoma, with 1-3 V/cm often cited as the range of threshold intensities for antitumor effects. However, the field amplitudes required for maximal impact and strategies needed to achieve them in the brain remain poorly defined. This study aimed to evaluate the safety, electrical integrity, field distribution, and efficacy of a novel implanted Intratumoral Modulation Therapy (IMT) delivering spatiotemporally dynamic electric fields in an aggressive in vivo glioblastoma model.

METHODS

IMT was evaluated in the rat F98 glioblastoma model using implanted intracerebral electrodes delivering continuous 200 kHz dynamic electric fields for 7 days. Electric field distributions were assessed with finite-element simulations and direct electrical measurements. Tumor response was quantified via bioluminescence and magnetic resonance imaging. Tissue impedance, delivered voltage, and in vivo brain temperature were monitored during IMT.

RESULTS

IMT produced no neurological adverse effects or imaging evidence of brain injury. Tumor progression was significantly suppressed, with 8-fold reduction in bioluminescence progression and 5-fold reduction in magnetic resonance imaging-measured tumor volume growth. Broad tumor and peritumoral regions received fields of >1 V/cm, while localized intratumoral regions reached 5-8 V/cm, confirmed by simulation and direct measurement. Mean brain temperature within the central field increased by 1°C.

CONCLUSIONS

Multi-electrode IMT generated broad, spatiotemporally dynamic electric fields that safely exceeded putative amplitude thresholds and significantly attenuated glioblastoma growth in vivo. These findings suggest that implantable delivery strategies have potential to broaden the therapeutic parameter space and enhance the efficacy of electric field-based glioblastoma interventions.