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

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Abstract

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.

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Abbreviations

API:

Average peritumoral intensity

CSF:

Cerebrospinal fluid

FEM:

Finite element methods

GM:

Gray matter

mOS:

Median overall survival

MTL:

Multiple-tissue-layer model

GBM:

Glioblastoma

PEEK:

Polyetheretherketone

RH:

Realistic head

SR:

Skull remodeling

TMZ:

Temozolomide

TTFields:

Tumor treating fields

WM:

White matter

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Acknowledgements

We thank Yuge Yao from the Department of Energy and Power Engineering, Tsinghua University for revising the methods and language editings.

Funding

This work was funded by the National Natural Science Foundation of China (Grant No. 82151302); Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (Grant No. 20191080597, 2019ZLH101).

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Author notes

  1. Xin Yang and Penghao Liu contributed equally to this work.

Authors and Affiliations

  1. National Engineering Research Center of Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing, 100084, China

    Xin Yang, Xiaoyan Wen, Chunhua Hu & Luming Li

  2. Departments of Neurosurgery, Peking Union Medical College Hospital (East), Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China

    Penghao Liu, Hao Xing, Yu Wang & Wenbin Ma

  3. Precision Medicine & Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, 518071, China

    Luming Li

  4. IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China

    Luming Li

  5. Institute of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100093, China

    Luming Li

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  1. Xin Yang
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Contributions

XY and PL designed the research; XY and XW conducted the simulation and calculation; XY and PL wrote and revised the article; CH supervised the study protocol and provide guidance in model validation; WM, YW, and HX provided clinical expertise in TTFields application and SR surgery; LL and CH provide mechanical expertise in TTFields design; CH, WM and LL provided funding and correspondence to this article. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Chunhua Hu, Luming Li or Wenbin Ma.

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Written consent was acquired on the open access and publishment of his imaging data (www.simnibs.org).

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Yang, X., Liu, P., Xing, H. et al. Skull modulated strategies to intensify tumor treating fields on brain tumor: a finite element study. Biomech Model Mechanobiol 21, 1133–1144 (2022). https://doi.org/10.1007/s10237-022-01580-7

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