Purpose: Tumor-treating fields (TTFields) are an antimitotic treatment modality that interfere with glioblastoma (GBM) 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 GBM.
Methods And Materials: Magnetic resonance images of 428 newly diagnosed GBM patients who 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 element method. The TTFields dose was calculated within regions of the tumor bed and normal brain, and its relationship with progression was determined.
Results: Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at greater 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 with normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of the enhancing tumor that returned to normal was significantly higher than in the areas of the 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 the TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression.
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http://dx.doi.org/10.1016/j.ijrobp.2021.12.152 | DOI Listing |
Oncologist
October 2024
Department of Neuro-Oncology, Saint Luke's Cancer Institute, Kansas City, MO, United States.
Neurooncol Adv
March 2024
Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry.
View Article and Find Full Text PDFCell Death Discov
October 2022
Department of Oncology, Xiangya Hospital, Central South University, 410008, Changsha, China.
Tumor Treating Fields (TTFields) is a physical therapy that uses moderate frequency (100-300 kHz) and low-intensity (1-3 V/cm) alternating electric fields to inhibit tumors. Currently, the Food and Drug Administration approves TTFields for treating recurrent or newly diagnosed glioblastoma (GBM) and malignant pleural mesothelioma (MPM). The classical mechanism of TTFields is mitotic inhibition by hindering the formation of tubulin and spindle.
View Article and Find Full Text PDFChin Neurosurg J
September 2022
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
TTFields is a novel treating modality of glioblastoma (GBM) which can significantly prolong the overall survival (OS) of newly diagnosed or recurrent glioblastoma. Some researchers have revealed that a variety of factors can affect the efficacy of TTFields. So, we review the available literature about the influencing factors on efficacy of TTFields and then choose two experimentally supported factors: the dose of dexamethasone and compliance of TTFields to perform a meta-analysis.
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