The Impact of Tumor Treating Fields on Glioblastoma Progression Patterns

Martin Glas, Matthew T Ballo, Ze'ev Bomzon, Noa Urman, Shay Levi, Gitit Lavy-Shahaf, Suriya Jeyapalan, Terence T Sio, Paul M DeRose, Martin Misch, Sophie Taillibert, Zvi Ram, Andreas F Hottinger, Jacob Easaw, Chae-Yong Kim, Suyash Mohan, Roger Stupp

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose-density at the tumor bed and survival in patients treated with TTFields. This study tests the hypothesis that the antimitotic effects of TTFields result in measurable changes in the location and patterns of progression of newly diagnosed glioblastoma (nGBM) patients.

METHODS: MRI images of 428 nGBM patients that participated in the pivotal EF-14 trial were reviewed and the rates at which distant progression occurred in the TTFields treatment and control arm were compared. Realistic head models of 252 TTFields treated patients were created and TTFields intensity distributions were calculated using a Finite Elements Method. TTFields dose was calculated within regions of the tumor bed and normal brain and its relationship with progression determined.

RESULTS: Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at larger distances from the primary lesion than in the control arm. Distant progression correlated with improved clinical outcome in the TTFields patients, with no such correlation observed in the controls. Areas of normal brain that remained normal were exposed to higher TTFields doses compared to normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of enhancing tumor that returned to normal was significantly higher than in the areas of normal brain that progressed to enhancing tumor.

CONCLUSIONS: There was a direct correlation between TTFields dose distribution and tumor response, confirming the therapeutic activity of TTFields and the rationale for optimizing array placement to maximize TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression.

Original languageEnglish
JournalInternational Journal of Radiation Oncology, Biology, Physics
DOIs
StateE-pub ahead of print - 26 Dec 2021

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