Abstract

Abstract INTRODUCTION This study aims to investigate the molecular characterization of glioma tissue after treatment with Tumor Treating Fields (TTFields). TTFields therapy utilizes low-intensity alternating electric fields to disrupt cancer cell division and is approved for treatment of glioblastoma as well as mesothelioma. Understanding the histological, cellular, and epigenetic changes induced by TTFields treatment can help identify biomarkers for TTFields response and elucidate potential resistance mechanisms. MATERIAL AND METHODS Tumor tissue samples (FFPE) were collected from newly diagnosed glioblastoma patients treated with TTFields, including both the primary tumor and matching recurrent tumor samples. Molecular analyses using a glioma-targeted next-generation sequencing (NGS) panel sequencing were performed to assess genetic alterations in both primary and recurrent tumors. RESULTS Genomic analysis of paired samples from 5 patients (4 glioblastoma, one astrocytoma, IDH-mutated WHO grade 4) revealed an identical molecular pattern (TERT mutation) in 2 patients, one patient with a gain of an ATRX mutation in the recurrent tumor, one patient with gain of two EGFR mutations, and the IDH1-mutated astrocytoma showing a loss of a TP53 mutation in the recurrent tumor. CONCLUSION This pilot study provides valuable insights into the molecular characterization of glioma tissue after TTFields treatment. It appears that the spectrum of mutations may vary in a substantial number of TTF-treated tumors. Further validation and larger-scale studies are needed to confirm and expand upon these preliminary results.

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