Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study.
OBJECTIVE
The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer.


METHODS
We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios.


RESULTS
For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60-70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30-50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50-70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect.


CONCLUSIONS
Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in healthy tissues. A clinical trial is being planned to validate safety and efficacy.
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Anders Rosendal
AR
Korshoej
The Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
Guilherme Bicalho
GB
Saturnino
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Line Kirkegaard
LK
Rasmussen
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Gorm
G
von Oettingen
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Jens Christian Hedemann
JC
Sørensen
The Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Max Planck Institute for Biological Cybernetics, Tübingen, Germany.|Biomedical Engineering, DTU Elektro, Technical University of Denmark, Kongens Lyngby, Denmark.
Axel
A
Thielscher
D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D003198:Computer Simulation; D003399:Craniotomy; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000601:surgery*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008953:Models, Anatomic; D060787:Neoplasm Grading; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
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