Abstract
Abstract INTRODUCTION A recent post-hoc analysis of the EF-14 phase 3 trial showed a connection between TTFields dose at the tumor and Overall Survival in new diagnosed Glioblastoma (ndGBM) patients [1]. Here we expand the results of that study and show a connection between TTFields dose distribution in the brain and progression patterns in ndGBM patients. METHODS Participants of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=306/466, control: N=122/229). Enhancing tumor was segmented on T1c MRIs at baseline and progression. Regions of progression disconnected from the original lesion were defined as distal. The rates of occurrence and distances of distal progressions from primary lesions were compared between the arms. Computational head models were created and delivery of TTFields numerically simulated for n=229 patients in treatment for over 2. Dose in regions of progression was compared to dose in regions where no progression occurred. RESULTS The median distance between primary and distal lesions was larger in the treatment arm (control: 14.2±14.4 mm, TTFields 23.2±29.8 mm, p=0.03 Wilcoxon rank-sum). A higher rate of distal progression outside of a 20mm boundary zone around the primary lesion was observed in the treatment arm. (Control: 10/122, TTFields: 53/306 p< 0.02 chi-squared). In proximity to the primary lesion (a 3 mm ring around the tumor), TTFields dose was lower in regions of progression than in regions where no progression occurred (0.73 mW/cm^3 vs. 0.79 mW/cm^3 p< 0.0001 t-test) DISCUSSION AND CONCLUSIONS This study suggests that TTFields alters progression patterns and that progression is more likely to occur in regions exposed to low TTFields dose. The study emphasizes the rationale for adaptive TTFields treatment planning targeting regions of progression. [1] Ballo et. al., IJROBP (2019)
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