Optimization strategy of tumor-treating fields lowering the risk of distal progression of glioblastoma: A preliminary in-silico study

Chae-Bin Song, Jongseung Lee, Hyungtaek Kim, Donghyeon Kim Brain Stimulation | 발행연도 2023.02.18



Tumor-treating fields (TTFields) are a glioblastoma (GBM) treatment that prevents local progression (LP) of GBM. TTFields are delivered at a frequency of 200kHz with a current of 1.8A using two pairs of 3x3 transducer arrays. Prior studies suggest that the orthogonality of the electric fields (E-field) and a threshold of E-field intensity (106V/m) are key factors determining TTFields efficacy. However, studies underestimated a factor associated with distal progression (DP) in normal tissue. We expect increasing the ratio of the normal tissue with the E-field above the threshold (RNTAT) may help prevent DP. In this study, we simulated the personalized transducer layout considering RNTAT, besides considering the orthogonality and the E-field intensity at the GBM.

We created realistic head models from T1-MRI of GBM patients (n=2). Initial array positions were determined based on the GBM location. We then optimized the array position following three criteria: orthogonality of the E-fields (P1), the E-field intensity (P2) at the GBM, and RNTAT (P3). Each criterion was rescaled into [0,1] and the sum of the rescaled value was compared to evaluate TTFields efficacy. We tested set of conditions when DP-factor was not considered (C1:P1+P2) and considered (C2:P1+P2+P3). The candidates with the highest score in C1 and C2 were selected.

The observed data seem to indicate that the optimized arrays increased TTFields efficacy for LP greater than 2-fold. While the effect on LP was maintained (C1: 1.97±0.04, C2: 1.87±0.02), we found that P3 can be decreased if not considered as an optimization parameter.

The simulation result may indicate that optimizing TTFields considering P3 may be required to lower DP of GBM. However, it remains to be seen if the observed results can be translated to clinical outcomes. Future research is necessary to optimize TTFields efficacy based on the power loss density at the GBM.