The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) or supra-poration to cause cell death in treated tumors. In embodiments, the methods comprise the integration of ultra-short electric pulses, both temporally and spatially, to achieve the desired modality of cell death.