Skull modulated strategies to intensify tumor treating fields on brain tumor: a finite element study

Tumor treating fields (TTFields) are a breakthrough in treating glioblastoma (GBM), whereas the intensity cannot be further enhanced, due to the limitation of scalp lesions. Skull remodeling (SR) surgery can elevate the treatment dose of TTFields in the intracranial foci. This study was aimed at exploring the characteristics of the skull modulated strategies toward TTFields augmentation. The simplified multiple-tissue-layer model (MTL) and realistic head (RH) model were reconstructed through finite element methods (FEM), to simulate the remodeling of the skull, which included skull drilling, thinning, and cranioplasty with PEEK, titanium, cerebrospinal fluid (CSF), connective tissue and autologous bone. Skull thinning could enhance the intensity of TTFields in the brain tumor, with a 10% of increase in average peritumoral intensity (API) by every 1 cm decrease in skull thickness. Cranioplasty with titanium accompanied the most enhancement of TTFields in the MTL model, but CSF was superior in TTFields enhancement when simulated in the RH model. Besides, API increased nonlinearly with the expansion of drilled burr holes. In comparison with the single drill replaced by titanium, nine burr holes could reach 96.98% of enhancement in API, but it could only reach 63.08% of enhancement under craniectomy of nine times skull defect area. Skull thinning and drilling could enhance API, which was correlated with the number and area of skull drilling. Cranioplasty with highly conductive material could also augment API, but might not provide clinical benefits as expected.