Effects of craniectomy defect on tumor-treating fields

Tumor-treating fields (TTFields) are alternating electric fields approved for the treatment of glioblastoma. They must penetrate through the skull to reach the gross tumor volume (GTV) in the brain. Since the skull is an attenuator of electric fields, removal of a section of cortical bone by craniectomy may facilitate the delivery of TTFields into the GTV.

We identified a glioblastoma patient who underwent craniectomy for evacuation of a subdural empyema. The patient subsequently received standard adjuvant treatment with TTFields plus temozolomide without replacement of the skull defect. Post-acquisition magnetic resonance imaging datasets were obtained from this index patient and 2 others for virtual craniectomy analysis. After anatomic delineation, a 3-dimensional finite element mesh was generated and then solved for the distribution of applied electric fields, rate of energy deposition, and current density at the GTV.

The geometry of craniectomy defect alone, with or without burr holes, did not alter TTFields delivery to GTV. Biomaterials filling the defect could significantly influence electric field penetration, particularly when they are highly conductive at 10 S/m or 7.76 × 10⁶ S/m as in tantalum. The ratio of GTV relative to defect size also enhanced or attenuated TTFields coverage when the GTV was expanded or eroded, respectively.

Craniectomy, biomaterials filling the defect, and the ratio of GTV relative to defect size may interact in a combinatorial fashion in modulating TTFields penetration into the brain. These findings are clinically relevant for personalized TTFields treatment.